Daily Papers

We propose expanding the shared Transformer module to produce and initialize Transformers of varying depths, enabling adaptation to diverse resource constraints. Drawing an analogy to genetic expansibility, we term such module as learngene. To identify the expansion mechanism, we delve into the relationship between the layer's position and its corresponding weight value, and find that linear function appropriately approximates this relationship. Building on this insight, we present Transformer as Linear Expansion of learnGene (TLEG), a novel approach for flexibly producing and initializing Transformers of diverse depths. Specifically, to learn learngene, we firstly construct an auxiliary Transformer linearly expanded from learngene, after which we train it through employing soft distillation. Subsequently, we can produce and initialize Transformers of varying depths via linearly expanding the well-trained learngene, thereby supporting diverse downstream scenarios. Extensive experiments on ImageNet-1K demonstrate that TLEG achieves comparable or better performance in contrast to many individual models trained from scratch, while reducing around 2x training cost. When transferring to several downstream classification datasets, TLEG surpasses existing initialization methods by a large margin (e.g., +6.87% on iNat 2019 and +7.66% on CIFAR-100). Under the situation where we need to produce models of varying depths adapting for different resource constraints, TLEG achieves comparable results while reducing around 19x parameters stored to initialize these models and around 5x pre-training costs, in contrast to the pre-training and fine-tuning approach. When transferring a fixed set of parameters to initialize different models, TLEG presents better flexibility and competitive performance while reducing around 2.9x parameters stored to initialize, compared to the pre-training approach.

In practice, we usually need to build variable-sized models adapting for diverse resource constraints in different application scenarios, where weight initialization is an important step prior to training. The Learngene framework, introduced recently, firstly learns one compact part termed as learngene from a large well-trained model, after which learngene is expanded to initialize variable-sized models. In this paper, we start from analysing the importance of guidance for the expansion of well-trained learngene layers, inspiring the design of a simple but highly effective Learngene approach termed SWS (Stage-wise Weight Sharing), where both learngene layers and their learning process critically contribute to providing knowledge and guidance for initializing models at varying scales. Specifically, to learn learngene layers, we build an auxiliary model comprising multiple stages where the layer weights in each stage are shared, after which we train it through distillation. Subsequently, we expand these learngene layers containing stage information at their corresponding stage to initialize models of variable depths. Extensive experiments on ImageNet-1K demonstrate that SWS achieves consistent better performance compared to many models trained from scratch, while reducing around 6.6x total training costs. In some cases, SWS performs better only after 1 epoch tuning. When initializing variable-sized models adapting for different resource constraints, SWS achieves better results while reducing around 20x parameters stored to initialize these models and around 10x pre-training costs, in contrast to the pre-training and fine-tuning approach.

Recently, Stitchable Neural Networks (SN-Net) is proposed to stitch some pre-trained networks for quickly building numerous networks with different complexity and performance trade-offs. In this way, the burdens of designing or training the variable-sized networks, which can be used in application scenarios with diverse resource constraints, are alleviated. However, SN-Net still faces a few challenges. 1) Stitching from multiple independently pre-trained anchors introduces high storage resource consumption. 2) SN-Net faces challenges to build smaller models for low resource constraints. 3). SN-Net uses an unlearned initialization method for stitch layers, limiting the final performance. To overcome these challenges, motivated by the recently proposed Learngene framework, we propose a novel method called Learngene Pool. Briefly, Learngene distills the critical knowledge from a large pre-trained model into a small part (termed as learngene) and then expands this small part into a few variable-sized models. In our proposed method, we distill one pretrained large model into multiple small models whose network blocks are used as learngene instances to construct the learngene pool. Since only one large model is used, we do not need to store more large models as SN-Net and after distilling, smaller learngene instances can be created to build small models to satisfy low resource constraints. We also insert learnable transformation matrices between the instances to stitch them into variable-sized models to improve the performance of these models. Exhaustive experiments have been implemented and the results validate the effectiveness of the proposed Learngene Pool compared with SN-Net.

The success of the GPT series proves that GPT can extract general information from sequences, thereby benefiting all downstream tasks. This motivates us to use pre-trained models to explore the hidden information in DNA sequences. However, data and task requirements in DNA sequence analysis are complexity and diversity as DNA relevant data includes different types of information, such as sequences, expression levels, etc, while there is currently no model specifically designed for these characteristics. Hereby, we present DNAGPT, a generalized foundation model pre-trained on over 10 billion base pairs from 9 species which can be fine-tuned for any DNA sequence analysis task. Our model can simultaneously process or output DNA sequences and numbers. In addition, our unique token design allows users to design prompts according to their own task requirements, making it applicable to any type of task. We have evaluated our model on classification, regression, and generation tasks. We demonstrate that DNAGPT benefits from pre-training, and therefore can bring performance gains to any downstream task. Our model is not only a new attempt in the field of genomes analysis, but also provides a new direction for the application of foundation models in biology.

We pretrain METAGENE-1, a 7-billion-parameter autoregressive transformer model, which we refer to as a metagenomic foundation model, on a novel corpus of diverse metagenomic DNA and RNA sequences comprising over 1.5 trillion base pairs. This dataset is sourced from a large collection of human wastewater samples, processed and sequenced using deep metagenomic (next-generation) sequencing methods. Unlike genomic models that focus on individual genomes or curated sets of specific species, the aim of METAGENE-1 is to capture the full distribution of genomic information present within this wastewater, to aid in tasks relevant to pandemic monitoring and pathogen detection. We carry out byte-pair encoding (BPE) tokenization on our dataset, tailored for metagenomic sequences, and then pretrain our model. In this paper, we first detail the pretraining dataset, tokenization strategy, and model architecture, highlighting the considerations and design choices that enable the effective modeling of metagenomic data. We then show results of pretraining this model on our metagenomic dataset, providing details about our losses, system metrics, and training stability over the course of pretraining. Finally, we demonstrate the performance of METAGENE-1, which achieves state-of-the-art results on a set of genomic benchmarks and new evaluations focused on human-pathogen detection and genomic sequence embedding, showcasing its potential for public health applications in pandemic monitoring, biosurveillance, and early detection of emerging health threats.

Advancements in DNA sequencing technologies have significantly improved our ability to decode genomic sequences. However, the prediction and interpretation of these sequences remain challenging due to the intricate nature of genetic material. Large language models (LLMs) have introduced new opportunities for biological sequence analysis. Recent developments in genomic language models have underscored the potential of LLMs in deciphering DNA sequences. Nonetheless, existing models often face limitations in robustness and application scope, primarily due to constraints in model structure and training data scale. To address these limitations, we present GENERator, a generative genomic foundation model featuring a context length of 98k base pairs (bp) and 1.2B parameters. Trained on an expansive dataset comprising 386B bp of eukaryotic DNA, the GENERator demonstrates state-of-the-art performance across both established and newly proposed benchmarks. The model adheres to the central dogma of molecular biology, accurately generating protein-coding sequences that translate into proteins structurally analogous to known families. It also shows significant promise in sequence optimization, particularly through the prompt-responsive generation of promoter sequences with specific activity profiles. These capabilities position the GENERator as a pivotal tool for genomic research and biotechnological advancement, enhancing our ability to interpret and predict complex biological systems and enabling precise genomic interventions.

Attention-based models trained on protein sequences have demonstrated incredible success at classification and generation tasks relevant for artificial intelligence-driven protein design. However, we lack a sufficient understanding of how very large-scale models and data play a role in effective protein model development. We introduce a suite of protein language models, named ProGen2, that are scaled up to 6.4B parameters and trained on different sequence datasets drawn from over a billion proteins from genomic, metagenomic, and immune repertoire databases. ProGen2 models show state-of-the-art performance in capturing the distribution of observed evolutionary sequences, generating novel viable sequences, and predicting protein fitness without additional finetuning. As large model sizes and raw numbers of protein sequences continue to become more widely accessible, our results suggest that a growing emphasis needs to be placed on the data distribution provided to a protein sequence model. We release the ProGen2 models and code at https://github.com/salesforce/progen.

While large language models (LLMs) have been successfully applied to various tasks, they still face challenges with hallucinations. Augmenting LLMs with domain-specific tools such as database utilities can facilitate easier and more precise access to specialized knowledge. In this paper, we present GeneGPT, a novel method for teaching LLMs to use the Web APIs of the National Center for Biotechnology Information (NCBI) for answering genomics questions. Specifically, we prompt Codex to solve the GeneTuring tests with NCBI Web APIs by in-context learning and an augmented decoding algorithm that can detect and execute API calls. Experimental results show that GeneGPT achieves state-of-the-art performance on eight tasks in the GeneTuring benchmark with an average score of 0.83, largely surpassing retrieval-augmented LLMs such as the new Bing (0.44), biomedical LLMs such as BioMedLM (0.08) and BioGPT (0.04), as well as GPT-3 (0.16) and ChatGPT (0.12). Our further analyses suggest that: (1) API demonstrations have good cross-task generalizability and are more useful than documentations for in-context learning; (2) GeneGPT can generalize to longer chains of API calls and answer multi-hop questions in GeneHop, a novel dataset introduced in this work; (3) Different types of errors are enriched in different tasks, providing valuable insights for future improvements.

Building a general-purpose task model similar to ChatGPT has been an important research direction for gene large language models. Instruction fine-tuning is a key component in building ChatGPT, but existing instructions are primarily based on natural language. Natural language and gene sequences have significant differences in tokenization and encoding. Therefore, constructing a multilingual model that can handle both natural language and gene sequences is crucial for solving this problem.In this paper, we expand the capabilities of the LLaMA large language model to include gene language. This involves expanding the vocabulary using the Byte Pair Encoding (BPE) method, specifically tailored for DNA and protein sequences, and conducting further pre-training on these sequences. We then convert various downstream gene task data into a unified format for instruction fine-tuning and further fine-tune the model on this data.Our study demonstrates that a mixed model of gene and natural language, fine-tuned with instructions, achieves results comparable to the current state-of-the-art (SOTA) in tasks such as gene classification and gene sequence interaction. This provides a promising direction for building a unified large language model for gene tasks.

Genomic (DNA) sequences encode an enormous amount of information for gene regulation and protein synthesis. Similar to natural language models, researchers have proposed foundation models in genomics to learn generalizable features from unlabeled genome data that can then be fine-tuned for downstream tasks such as identifying regulatory elements. Due to the quadratic scaling of attention, previous Transformer-based genomic models have used 512 to 4k tokens as context (<0.001% of the human genome), significantly limiting the modeling of long-range interactions in DNA. In addition, these methods rely on tokenizers to aggregate meaningful DNA units, losing single nucleotide resolution where subtle genetic variations can completely alter protein function via single nucleotide polymorphisms (SNPs). Recently, Hyena, a large language model based on implicit convolutions was shown to match attention in quality while allowing longer context lengths and lower time complexity. Leveraging Hyenas new long-range capabilities, we present HyenaDNA, a genomic foundation model pretrained on the human reference genome with context lengths of up to 1 million tokens at the single nucleotide-level, an up to 500x increase over previous dense attention-based models. HyenaDNA scales sub-quadratically in sequence length (training up to 160x faster than Transformer), uses single nucleotide tokens, and has full global context at each layer. We explore what longer context enables - including the first use of in-context learning in genomics for simple adaptation to novel tasks without updating pretrained model weights. On fine-tuned benchmarks from the Nucleotide Transformer, HyenaDNA reaches state-of-the-art (SotA) on 12 of 17 datasets using a model with orders of magnitude less parameters and pretraining data. On the GenomicBenchmarks, HyenaDNA surpasses SotA on all 8 datasets on average by +9 accuracy points.

Pre-trained models have become the preferred backbone due to the expansion of model parameters, with techniques like Parameter-Efficient Fine-Tuning (PEFTs) typically fixing the parameters of these models. However, pre-trained models may not always be optimal, especially when there are discrepancies between training tasks and target tasks, potentially resulting in negative transfer. To address this, we introduce KIND, which performs Knowledge INtegration and Diversion in diffusion models. KIND first integrates knowledge by decomposing parameter matrices of models using U, Sigma, and V matrices, formally inspired by singular value decomposition (SVD). Then it explicitly partitions the components of these matrices into learngenes and tailors to condense common and class-specific knowledge, respectively, through a class gate. In this way, KIND redefines traditional pre-training methods by adjusting training objectives from maximizing model performance on current tasks to condensing transferable common knowledge, leveraging the Learngene framework. We conduct experiments on ImageNet-1K and compare KIND with PEFT and other learngene methods. Results indicate that KIND achieves state-of-the-art performance compared to other PEFT and learngene methods. Specifically, the images generated by KIND achieves more than 6.54 and 1.07 decrease in FID and sFID on DiT-L/2, utilizing only 45.4M trainable parameters and saving at least 35.4G FLOPs in computational cost.

Protein modeling is an increasingly popular area of machine learning research. Semi-supervised learning has emerged as an important paradigm in protein modeling due to the high cost of acquiring supervised protein labels, but the current literature is fragmented when it comes to datasets and standardized evaluation techniques. To facilitate progress in this field, we introduce the Tasks Assessing Protein Embeddings (TAPE), a set of five biologically relevant semi-supervised learning tasks spread across different domains of protein biology. We curate tasks into specific training, validation, and test splits to ensure that each task tests biologically relevant generalization that transfers to real-life scenarios. We benchmark a range of approaches to semi-supervised protein representation learning, which span recent work as well as canonical sequence learning techniques. We find that self-supervised pretraining is helpful for almost all models on all tasks, more than doubling performance in some cases. Despite this increase, in several cases features learned by self-supervised pretraining still lag behind features extracted by state-of-the-art non-neural techniques. This gap in performance suggests a huge opportunity for innovative architecture design and improved modeling paradigms that better capture the signal in biological sequences. TAPE will help the machine learning community focus effort on scientifically relevant problems. Toward this end, all data and code used to run these experiments are available at https://github.com/songlab-cal/tape.

Pre-trained language models have attracted increasing attention in the biomedical domain, inspired by their great success in the general natural language domain. Among the two main branches of pre-trained language models in the general language domain, i.e., BERT (and its variants) and GPT (and its variants), the first one has been extensively studied in the biomedical domain, such as BioBERT and PubMedBERT. While they have achieved great success on a variety of discriminative downstream biomedical tasks, the lack of generation ability constrains their application scope. In this paper, we propose BioGPT, a domain-specific generative Transformer language model pre-trained on large scale biomedical literature. We evaluate BioGPT on six biomedical NLP tasks and demonstrate that our model outperforms previous models on most tasks. Especially, we get 44.98%, 38.42% and 40.76% F1 score on BC5CDR, KD-DTI and DDI end-to-end relation extraction tasks respectively, and 78.2% accuracy on PubMedQA, creating a new record. Our larger model BioGPT-Large achieves 81.0% on PubMedQA. Our case study on text generation further demonstrates the advantage of BioGPT on biomedical literature to generate fluent descriptions for biomedical terms. Code is available at https://github.com/microsoft/BioGPT.

Recently, sequence-to-sequence (seq2seq) models with the Transformer architecture have achieved remarkable performance on various conditional text generation tasks, such as machine translation. However, most of them are trained with teacher forcing with the ground truth label given at each time step, without being exposed to incorrectly generated tokens during training, which hurts its generalization to unseen inputs, that is known as the "exposure bias" problem. In this work, we propose to mitigate the conditional text generation problem by contrasting positive pairs with negative pairs, such that the model is exposed to various valid or incorrect perturbations of the inputs, for improved generalization. However, training the model with naive contrastive learning framework using random non-target sequences as negative examples is suboptimal, since they are easily distinguishable from the correct output, especially so with models pretrained with large text corpora. Also, generating positive examples requires domain-specific augmentation heuristics which may not generalize over diverse domains. To tackle this problem, we propose a principled method to generate positive and negative samples for contrastive learning of seq2seq models. Specifically, we generate negative examples by adding small perturbations to the input sequence to minimize its conditional likelihood, and positive examples by adding large perturbations while enforcing it to have a high conditional likelihood. Such "hard" positive and negative pairs generated using our method guides the model to better distinguish correct outputs from incorrect ones. We empirically show that our proposed method significantly improves the generalization of the seq2seq on three text generation tasks - machine translation, text summarization, and question generation.

Large Language Models (LLMs) have become ubiquitous across various domains, transforming the way we interact with information and conduct research. However, most high-performing LLMs remain confined behind proprietary walls, hindering scientific progress. Most open-source LLMs, on the other hand, are limited in their ability to support longer sequence lengths, which is a key requirement for many tasks that require inference over an input context. To address this, we have trained XGen, a series of 7B parameter models on up to 8K sequence length for up to 1.5T tokens. We have also finetuned the XGen models on public-domain instructional data, creating their instruction-tuned counterparts (XGen-Inst). We open-source our models for both research advancements and commercial applications. Our evaluation on standard benchmarks shows that XGen models achieve comparable or better results when compared with state-of-the-art open-source LLMs. Our targeted evaluation on long sequence modeling tasks shows the benefits of our 8K-sequence models over 2K-sequence open-source LLMs.

DNA sequence alignment involves assigning short DNA reads to the most probable locations on an extensive reference genome. This process is crucial for various genomic analyses, including variant calling, transcriptomics, and epigenomics. Conventional methods, refined over decades, tackle this challenge in 2 steps: genome indexing followed by efficient search to locate likely positions for given reads. Building on the success of Large Language Models in encoding text into embeddings, where the distance metric captures semantic similarity, recent efforts have explored whether the same Transformer architecture can produce embeddings for DNA sequences. Such models have shown early promise in classifying short DNA sequences, such as detecting coding/non-coding regions, and enhancer, promoter sequences. However, performance at sequence classification tasks does not translate to sequence alignment, where it is necessary to search across the genome to align each read, a significantly longer-range task. We bridge this gap by framing the Sequence Alignment task for Transformer models as an "Embed-Search-Align" task. In this framework, a novel Reference-Free DNA Embedding model generates embeddings of reads and reference fragments, which are projected into a shared vector space where the read-fragment distance is used as a surrogate for alignment. Technical contributions include: (1) Contrastive loss for self-supervised training of DNA sequence representations, facilitating rich reference-free, sequence-level embeddings, and (2) a DNA vector store to enable search across fragments on a global scale. DNA-ESA is 99% accurate when aligning 250-length reads onto a human genome (3gb), rivaling conventional methods such as Bowtie and BWA-Mem. DNA-ESA exceeds the performance of 6 Transformer model baselines such as Nucleotide Transformer, Hyena-DNA, and shows task transfer across chromosomes and species.

This paper presents the system description of our entry for the COLING 2025 RegNLP RIRAG (Regulatory Information Retrieval and Answer Generation) challenge, focusing on leveraging advanced information retrieval and answer generation techniques in regulatory domains. We experimented with a combination of embedding models, including Stella, BGE, CDE, and Mpnet, and leveraged fine-tuning and reranking for retrieving relevant documents in top ranks. We utilized a novel approach, LeSeR, which achieved competitive results with a recall@10 of 0.8201 and map@10 of 0.6655 for retrievals. This work highlights the transformative potential of natural language processing techniques in regulatory applications, offering insights into their capabilities for implementing a retrieval augmented generation system while identifying areas for future improvement in robustness and domain adaptation.

Recent proprietary large language models (LLMs), such as GPT-4, have achieved a milestone in tackling diverse challenges in the biomedical domain, ranging from multiple-choice questions to long-form generations. To address challenges that still cannot be handled with the encoded knowledge of LLMs, various retrieval-augmented generation (RAG) methods have been developed by searching documents from the knowledge corpus and appending them unconditionally or selectively to the input of LLMs for generation. However, when applying existing methods to different domain-specific problems, poor generalization becomes apparent, leading to fetching incorrect documents or making inaccurate judgments. In this paper, we introduce Self-BioRAG, a framework reliable for biomedical text that specializes in generating explanations, retrieving domain-specific documents, and self-reflecting generated responses. We utilize 84k filtered biomedical instruction sets to train Self-BioRAG that can assess its generated explanations with customized reflective tokens. Our work proves that domain-specific components, such as a retriever, domain-related document corpus, and instruction sets are necessary for adhering to domain-related instructions. Using three major medical question-answering benchmark datasets, experimental results of Self-BioRAG demonstrate significant performance gains by achieving a 7.2% absolute improvement on average over the state-of-the-art open-foundation model with a parameter size of 7B or less. Overall, we analyze that Self-BioRAG finds the clues in the question, retrieves relevant documents if needed, and understands how to answer with information from retrieved documents and encoded knowledge as a medical expert does. We release our data and code for training our framework components and model weights (7B and 13B) to enhance capabilities in biomedical and clinical domains.

Learning effective protein representations is critical in a variety of tasks in biology such as predicting protein function or structure. Existing approaches usually pretrain protein language models on a large number of unlabeled amino acid sequences and then finetune the models with some labeled data in downstream tasks. Despite the effectiveness of sequence-based approaches, the power of pretraining on known protein structures, which are available in smaller numbers only, has not been explored for protein property prediction, though protein structures are known to be determinants of protein function. In this paper, we propose to pretrain protein representations according to their 3D structures. We first present a simple yet effective encoder to learn the geometric features of a protein. We pretrain the protein graph encoder by leveraging multiview contrastive learning and different self-prediction tasks. Experimental results on both function prediction and fold classification tasks show that our proposed pretraining methods outperform or are on par with the state-of-the-art sequence-based methods, while using much less pretraining data. Our implementation is available at https://github.com/DeepGraphLearning/GearNet.

Training keyphrase generation (KPG) models require a large amount of annotated data, which can be prohibitively expensive and often limited to specific domains. In this study, we first demonstrate that large distribution shifts among different domains severely hinder the transferability of KPG models. We then propose a three-stage pipeline, which gradually guides KPG models' learning focus from general syntactical features to domain-related semantics, in a data-efficient manner. With Domain-general Phrase pre-training, we pre-train Sequence-to-Sequence models with generic phrase annotations that are widely available on the web, which enables the models to generate phrases in a wide range of domains. The resulting model is then applied in the Transfer Labeling stage to produce domain-specific pseudo keyphrases, which help adapt models to a new domain. Finally, we fine-tune the model with limited data with true labels to fully adapt it to the target domain. Our experiment results show that the proposed process can produce good-quality keyphrases in new domains and achieve consistent improvements after adaptation with limited in-domain annotated data. All code and datasets are available at https://github.com/memray/OpenNMT-kpg-release.

Pretraining large neural language models, such as BERT, has led to impressive gains on many natural language processing (NLP) tasks. However, most pretraining efforts focus on general domain corpora, such as newswire and Web. A prevailing assumption is that even domain-specific pretraining can benefit by starting from general-domain language models. In this paper, we challenge this assumption by showing that for domains with abundant unlabeled text, such as biomedicine, pretraining language models from scratch results in substantial gains over continual pretraining of general-domain language models. To facilitate this investigation, we compile a comprehensive biomedical NLP benchmark from publicly-available datasets. Our experiments show that domain-specific pretraining serves as a solid foundation for a wide range of biomedical NLP tasks, leading to new state-of-the-art results across the board. Further, in conducting a thorough evaluation of modeling choices, both for pretraining and task-specific fine-tuning, we discover that some common practices are unnecessary with BERT models, such as using complex tagging schemes in named entity recognition (NER). To help accelerate research in biomedical NLP, we have released our state-of-the-art pretrained and task-specific models for the community, and created a leaderboard featuring our BLURB benchmark (short for Biomedical Language Understanding & Reasoning Benchmark) at https://aka.ms/BLURB.

In this paper, we present a simple and efficient GEC sequence tagger using a Transformer encoder. Our system is pre-trained on synthetic data and then fine-tuned in two stages: first on errorful corpora, and second on a combination of errorful and error-free parallel corpora. We design custom token-level transformations to map input tokens to target corrections. Our best single-model/ensemble GEC tagger achieves an F_{0.5} of 65.3/66.5 on CoNLL-2014 (test) and F_{0.5} of 72.4/73.6 on BEA-2019 (test). Its inference speed is up to 10 times as fast as a Transformer-based seq2seq GEC system. The code and trained models are publicly available.

Predicting gene function from its DNA sequence is a fundamental challenge in biology. Many deep learning models have been proposed to embed DNA sequences and predict their enzymatic function, leveraging information in public databases linking DNA sequences to an enzymatic function label. However, much of the scientific community's knowledge of biological function is not represented in these categorical labels, and is instead captured in unstructured text descriptions of mechanisms, reactions, and enzyme behavior. These descriptions are often captured alongside DNA sequences in biological databases, albeit in an unstructured manner. Deep learning of models predicting enzymatic function are likely to benefit from incorporating this multi-modal data encoding scientific knowledge of biological function. There is, however, no dataset designed for machine learning algorithms to leverage this multi-modal information. Here we propose a novel dataset and benchmark suite that enables the exploration and development of large multi-modal neural network models on gene DNA sequences and natural language descriptions of gene function. We present baseline performance on benchmarks for both unsupervised and supervised tasks that demonstrate the difficulty of this modeling objective, while demonstrating the potential benefit of incorporating multi-modal data types in function prediction compared to DNA sequences alone. Our dataset is at: https://hoarfrost-lab.github.io/BioTalk/.

This paper introduces diffusion protein language model (DPLM), a versatile protein language model that demonstrates strong generative and predictive capabilities for protein sequences. We first pre-train scalable DPLMs from evolutionary-scale protein sequences within a generative self-supervised discrete diffusion probabilistic framework, which generalizes language modeling for proteins in a principled way. After pre-training, DPLM exhibits the ability to generate structurally plausible, novel, and diverse protein sequences for unconditional generation. We further demonstrate the proposed diffusion generative pre-training makes DPLM possess a better understanding of proteins, making it a superior representation learner, which can be fine-tuned for various predictive tasks, comparing favorably to ESM2 (Lin et al., 2022). Moreover, DPLM can be tailored for various needs, which showcases its prowess of conditional generation in several ways: (1) conditioning on partial peptide sequences, e.g., generating scaffolds for functional motifs with high success rate; (2) incorporating other modalities as conditioner, e.g., structure-conditioned generation for inverse folding; and (3) steering sequence generation towards desired properties, e.g., satisfying specified secondary structures, through a plug-and-play classifier guidance. Code is released at https://github.com/bytedance/dplm.

Based on the BioBricks standard, restriction synthesis is a novel catabolic iterative DNA synthesis method that utilizes endonucleases to synthesize a query sequence from a reference sequence. In this work, the reference sequence is built from shorter subsequences by classifying them as applicable or inapplicable for the synthesis method using three different machine learning methods: Support Vector Machines (SVMs), random forest, and Convolution Neural Networks (CNNs). Before applying these methods to the data, a series of feature selection, curation, and reduction steps are applied to create an accurate and representative feature space. Following these preprocessing steps, three different pipelines are proposed to classify subsequences based on their nucleotide sequence and other relevant features corresponding to the restriction sites of over 200 endonucleases. The sensitivity using SVMs, random forest, and CNNs are 94.9%, 92.7%, 91.4%, respectively. Moreover, each method scores lower in specificity with SVMs, random forest, and CNNs resulting in 77.4%, 85.7%, and 82.4%, respectively. In addition to analyzing these results, the misclassifications in SVMs and CNNs are investigated. Across these two models, different features with a derived nucleotide specificity visually contribute more to classification compared to other features. This observation is an important factor when considering new nucleotide sensitivity features for future studies.

mRNA-based vaccines have become a major focus in the pharmaceutical industry. The coding sequence as well as the Untranslated Regions (UTRs) of an mRNA can strongly influence translation efficiency, stability, degradation, and other factors that collectively determine a vaccine's effectiveness. However, optimizing mRNA sequences for those properties remains a complex challenge. Existing deep learning models often focus solely on coding region optimization, overlooking the UTRs. We present Helix-mRNA, a structured state-space-based and attention hybrid model to address these challenges. In addition to a first pre-training, a second pre-training stage allows us to specialise the model with high-quality data. We employ single nucleotide tokenization of mRNA sequences with codon separation, ensuring prior biological and structural information from the original mRNA sequence is not lost. Our model, Helix-mRNA, outperforms existing methods in analysing both UTRs and coding region properties. It can process sequences 6x longer than current approaches while using only 10% of the parameters of existing foundation models. Its predictive capabilities extend to all mRNA regions. We open-source the model (https://github.com/helicalAI/helical) and model weights (https://huggingface.co/helical-ai/helix-mRNA).

Advancements in genomic research such as high-throughput sequencing techniques have driven modern genomic studies into "big data" disciplines. This data explosion is constantly challenging conventional methods used in genomics. In parallel with the urgent demand for robust algorithms, deep learning has succeeded in a variety of fields such as vision, speech, and text processing. Yet genomics entails unique challenges to deep learning since we are expecting from deep learning a superhuman intelligence that explores beyond our knowledge to interpret the genome. A powerful deep learning model should rely on insightful utilization of task-specific knowledge. In this paper, we briefly discuss the strengths of different deep learning models from a genomic perspective so as to fit each particular task with a proper deep architecture, and remark on practical considerations of developing modern deep learning architectures for genomics. We also provide a concise review of deep learning applications in various aspects of genomic research, as well as pointing out potential opportunities and obstacles for future genomics applications.

We study the pre-train + fine-tune strategy for data-to-text tasks. Our experiments indicate that text-to-text pre-training in the form of T5, enables simple, end-to-end transformer based models to outperform pipelined neural architectures tailored for data-to-text generation, as well as alternative language model based pre-training techniques such as BERT and GPT-2. Importantly, T5 pre-training leads to better generalization, as evidenced by large improvements on out-of-domain test sets. We hope our work serves as a useful baseline for future research, as transfer learning becomes ever more prevalent for data-to-text tasks.

Pre-trained language models like ChatGPT have significantly improved code generation. As these models scale up, there is an increasing need for the output to handle more intricate tasks. Moreover, in bioinformatics, generating functional programs poses additional notable challenges due to the amount of domain knowledge, the need for complicated data operations, and intricate functional dependencies between the operations. Here, we present BioCoder, a benchmark developed to evaluate existing pre-trained models in generating bioinformatics code. In relation to function-code generation, BioCoder covers potential package dependencies, class declarations, and global variables. It incorporates 1026 functions and 1243 methods in Python and Java from GitHub and 253 examples from the Rosalind Project. BioCoder incorporates a fuzz-testing framework for evaluation, and we have applied it to evaluate many models including InCoder, CodeGen, CodeGen2, SantaCoder, StarCoder, StarCoder+, InstructCodeT5+, and ChatGPT. Our detailed analysis of these models emphasizes the importance of domain knowledge, pragmatic code generation, and contextual understanding. Our dataset, benchmark, Docker images, and scripts required for testing are all available at https://github.com/gersteinlab/biocoder.

Large Language Models (LLMs) have revolutionized the field of natural language processing, but they fall short in comprehending biological sequences such as proteins. To address this challenge, we propose InstructProtein, an innovative LLM that possesses bidirectional generation capabilities in both human and protein languages: (i) taking a protein sequence as input to predict its textual function description and (ii) using natural language to prompt protein sequence generation. To achieve this, we first pre-train an LLM on both protein and natural language corpora, enabling it to comprehend individual languages. Then supervised instruction tuning is employed to facilitate the alignment of these two distinct languages. Herein, we introduce a knowledge graph-based instruction generation framework to construct a high-quality instruction dataset, addressing annotation imbalance and instruction deficits in existing protein-text corpus. In particular, the instructions inherit the structural relations between proteins and function annotations in knowledge graphs, which empowers our model to engage in the causal modeling of protein functions, akin to the chain-of-thought processes in natural languages. Extensive experiments on bidirectional protein-text generation tasks show that InstructProtein outperforms state-of-the-art LLMs by large margins. Moreover, InstructProtein serves as a pioneering step towards text-based protein function prediction and sequence design, effectively bridging the gap between protein and human language understanding.

Despite the recent advancements in Large Language Models (LLMs), which have significantly enhanced the generative capabilities for various NLP tasks, LLMs still face limitations in directly handling retrieval tasks. However, many practical applications demand the seamless integration of both retrieval and generation. This paper introduces a novel and efficient One-pass Generation and retrieval framework (OneGen), designed to improve LLMs' performance on tasks that require both generation and retrieval. The proposed framework bridges the traditionally separate training approaches for generation and retrieval by incorporating retrieval tokens generated autoregressively. This enables a single LLM to handle both tasks simultaneously in a unified forward pass. We conduct experiments on two distinct types of composite tasks, RAG and Entity Linking, to validate the pluggability, effectiveness, and efficiency of OneGen in training and inference. Furthermore, our results show that integrating generation and retrieval within the same context preserves the generative capabilities of LLMs while improving retrieval performance. To the best of our knowledge, OneGen is the first to enable LLMs to conduct vector retrieval during the generation.

The genome sequence contains the blueprint for governing cellular processes. While the availability of genomes has vastly increased over the last decades, experimental annotation of the various functional, non-coding and regulatory elements encoded in the DNA sequence remains both expensive and challenging. This has sparked interest in unsupervised language modeling of genomic DNA, a paradigm that has seen great success for protein sequence data. Although various DNA language models have been proposed, evaluation tasks often differ between individual works, and might not fully recapitulate the fundamental challenges of genome annotation, including the length, scale and sparsity of the data. In this study, we introduce BEND, a Benchmark for DNA language models, featuring a collection of realistic and biologically meaningful downstream tasks defined on the human genome. We find that embeddings from current DNA LMs can approach performance of expert methods on some tasks, but only capture limited information about long-range features. BEND is available at https://github.com/frederikkemarin/BEND.

Medical open-domain question answering demands substantial access to specialized knowledge. Recent efforts have sought to decouple knowledge from model parameters, counteracting architectural scaling and allowing for training on common low-resource hardware. The retrieve-then-read paradigm has become ubiquitous, with model predictions grounded on relevant knowledge pieces from external repositories such as PubMed, textbooks, and UMLS. An alternative path, still under-explored but made possible by the advent of domain-specific large language models, entails constructing artificial contexts through prompting. As a result, "to generate or to retrieve" is the modern equivalent of Hamlet's dilemma. This paper presents MedGENIE, the first generate-then-read framework for multiple-choice question answering in medicine. We conduct extensive experiments on MedQA-USMLE, MedMCQA, and MMLU, incorporating a practical perspective by assuming a maximum of 24GB VRAM. MedGENIE sets a new state-of-the-art (SOTA) in the open-book setting of each testbed, even allowing a small-scale reader to outcompete zero-shot closed-book 175B baselines while using up to 706times fewer parameters. Overall, our findings reveal that generated passages are more effective than retrieved counterparts in attaining higher accuracy.

Pretrained language models have served as important backbones for natural language processing. Recently, in-domain pretraining has been shown to benefit various domain-specific downstream tasks. In the biomedical domain, natural language generation (NLG) tasks are of critical importance, while understudied. Approaching natural language understanding (NLU) tasks as NLG achieves satisfying performance in the general domain through constrained language generation or language prompting. We emphasize the lack of in-domain generative language models and the unsystematic generative downstream benchmarks in the biomedical domain, hindering the development of the research community. In this work, we introduce the generative language model BioBART that adapts BART to the biomedical domain. We collate various biomedical language generation tasks including dialogue, summarization, entity linking, and named entity recognition. BioBART pretrained on PubMed abstracts has enhanced performance compared to BART and set strong baselines on several tasks. Furthermore, we conduct ablation studies on the pretraining tasks for BioBART and find that sentence permutation has negative effects on downstream tasks.

Discovering mutations enhancing protein-protein interactions (PPIs) is critical for advancing biomedical research and developing improved therapeutics. While machine learning approaches have substantially advanced the field, they often struggle to generalize beyond training data in practical scenarios. The contributions of this work are three-fold. First, we construct PPIRef, the largest and non-redundant dataset of 3D protein-protein interactions, enabling effective large-scale learning. Second, we leverage the PPIRef dataset to pre-train PPIformer, a new SE(3)-equivariant model generalizing across diverse protein-binder variants. We fine-tune PPIformer to predict effects of mutations on protein-protein interactions via a thermodynamically motivated adjustment of the pre-training loss function. Finally, we demonstrate the enhanced generalization of our new PPIformer approach by outperforming other state-of-the-art methods on new, non-leaking splits of standard labeled PPI mutational data and independent case studies optimizing a human antibody against SARS-CoV-2 and increasing the thrombolytic activity of staphylokinase.

Discovering novel drug candidate molecules is one of the most fundamental and critical steps in drug development. Generative deep learning models, which create synthetic data given a probability distribution, have been developed with the purpose of picking completely new samples from a partially known space. Generative models offer high potential for designing de novo molecules; however, in order for them to be useful in real-life drug development pipelines, these models should be able to design target-specific molecules, which is the next step in this field. In this study, we propose DrugGEN, for the de novo design of drug candidate molecules that interact with selected target proteins. The proposed system represents compounds and protein structures as graphs and processes them via serially connected two generative adversarial networks comprising graph transformers. DrugGEN is trained using a large dataset of compounds from ChEMBL and target-specific bioactive molecules, to design effective and specific inhibitory molecules against the AKT1 protein, which has critical importance for developing treatments against various types of cancer. On fundamental benchmarks, DrugGEN models have either competitive or better performance against other methods. To assess the target-specific generation performance, we conducted further in silico analysis with molecular docking and deep learning-based bioactivity prediction. Results indicate that de novo molecules have high potential for interacting with the AKT1 protein structure in the level of its native ligand. DrugGEN can be used to design completely novel and effective target-specific drug candidate molecules for any druggable protein, given target features and a dataset of experimental bioactivities. Code base, datasets, results and trained models of DrugGEN are available at https://github.com/HUBioDataLab/DrugGEN

In this report, we introduce SciFive, a domain-specific T5 model that has been pre-trained on large biomedical corpora. Our model outperforms the current SOTA methods (i.e. BERT, BioBERT, Base T5) on tasks in named entity relation, relation extraction, natural language inference, and question-answering. We show that text-generation methods have significant potential in a broad array of biomedical NLP tasks, particularly those requiring longer, more complex outputs. Our results support the exploration of more difficult text generation tasks and the development of new methods in this area

Large Language Models (LLMs) have demonstrated remarkable proficiency in understanding and generating natural language. However, their capabilities wane in highly specialized domains underrepresented in the pretraining corpus, such as physical and biomedical sciences. This work explores how to repurpose general LLMs into effective task solvers for specialized domains. We introduce a novel, model-agnostic framework for learning custom input tags, which are parameterized as continuous vectors appended to the LLM's embedding layer, to condition the LLM. We design two types of input tags: domain tags are used to delimit specialized representations (e.g., chemical formulas) and provide domain-relevant context; function tags are used to represent specific functions (e.g., predicting molecular properties) and compress function-solving instructions. We develop a three-stage protocol to learn these tags using auxiliary data and domain knowledge. By explicitly disentangling task domains from task functions, our method enables zero-shot generalization to unseen problems through diverse combinations of the input tags. It also boosts LLM's performance in various specialized domains, such as predicting protein or chemical properties and modeling drug-target interactions, outperforming expert models tailored to these tasks.

Current protein language models (PLMs) learn protein representations mainly based on their sequences, thereby well capturing co-evolutionary information, but they are unable to explicitly acquire protein functions, which is the end goal of protein representation learning. Fortunately, for many proteins, their textual property descriptions are available, where their various functions are also described. Motivated by this fact, we first build the ProtDescribe dataset to augment protein sequences with text descriptions of their functions and other important properties. Based on this dataset, we propose the ProtST framework to enhance Protein Sequence pre-training and understanding by biomedical Texts. During pre-training, we design three types of tasks, i.e., unimodal mask prediction, multimodal representation alignment and multimodal mask prediction, to enhance a PLM with protein property information with different granularities and, at the same time, preserve the PLM's original representation power. On downstream tasks, ProtST enables both supervised learning and zero-shot prediction. We verify the superiority of ProtST-induced PLMs over previous ones on diverse representation learning benchmarks. Under the zero-shot setting, we show the effectiveness of ProtST on zero-shot protein classification, and ProtST also enables functional protein retrieval from a large-scale database without any function annotation.

Motivation: The development of novel compounds targeting proteins of interest is one of the most important tasks in the pharmaceutical industry. Deep generative models have been applied to targeted molecular design and have shown promising results. Recently, target-specific molecule generation has been viewed as a translation between the protein language and the chemical language. However, such a model is limited by the availability of interacting protein-ligand pairs. On the other hand, large amounts of unlabeled protein sequences and chemical compounds are available and have been used to train language models that learn useful representations. In this study, we propose exploiting pretrained biochemical language models to initialize (i.e. warm start) targeted molecule generation models. We investigate two warm start strategies: (i) a one-stage strategy where the initialized model is trained on targeted molecule generation (ii) a two-stage strategy containing a pre-finetuning on molecular generation followed by target specific training. We also compare two decoding strategies to generate compounds: beam search and sampling. Results: The results show that the warm-started models perform better than a baseline model trained from scratch. The two proposed warm-start strategies achieve similar results to each other with respect to widely used metrics from benchmarks. However, docking evaluation of the generated compounds for a number of novel proteins suggests that the one-stage strategy generalizes better than the two-stage strategy. Additionally, we observe that beam search outperforms sampling in both docking evaluation and benchmark metrics for assessing compound quality. Availability and implementation: The source code is available at https://github.com/boun-tabi/biochemical-lms-for-drug-design and the materials are archived in Zenodo at https://doi.org/10.5281/zenodo.6832145

Online education platforms are powered by various NLP pipelines, which utilize models like BERT to aid in content curation. Since the inception of the pre-trained language models like BERT, there have also been many efforts toward adapting these pre-trained models to specific domains. However, there has not been a model specifically adapted for the education domain (particularly K-12) across subjects to the best of our knowledge. In this work, we propose to train a language model on a corpus of data curated by us across multiple subjects from various sources for K-12 education. We also evaluate our model, K12-BERT, on downstream tasks like hierarchical taxonomy tagging.

Foundation models have revolutionized natural language processing and artificial intelligence, significantly enhancing how machines comprehend and generate human languages. Inspired by the success of these foundation models, researchers have developed foundation models for individual scientific domains, including small molecules, materials, proteins, DNA, and RNA. However, these models are typically trained in isolation, lacking the ability to integrate across different scientific domains. Recognizing that entities within these domains can all be represented as sequences, which together form the "language of nature", we introduce Nature Language Model (briefly, NatureLM), a sequence-based science foundation model designed for scientific discovery. Pre-trained with data from multiple scientific domains, NatureLM offers a unified, versatile model that enables various applications including: (i) generating and optimizing small molecules, proteins, RNA, and materials using text instructions; (ii) cross-domain generation/design, such as protein-to-molecule and protein-to-RNA generation; and (iii) achieving state-of-the-art performance in tasks like SMILES-to-IUPAC translation and retrosynthesis on USPTO-50k. NatureLM offers a promising generalist approach for various scientific tasks, including drug discovery (hit generation/optimization, ADMET optimization, synthesis), novel material design, and the development of therapeutic proteins or nucleotides. We have developed NatureLM models in different sizes (1 billion, 8 billion, and 46.7 billion parameters) and observed a clear improvement in performance as the model size increases.

We consider the problem of predicting gene expressions from DNA sequences. A key challenge of this task is to find the regulatory elements that control gene expressions. Here, we introduce Seq2Exp, a Sequence to Expression network explicitly designed to discover and extract regulatory elements that drive target gene expression, enhancing the accuracy of the gene expression prediction. Our approach captures the causal relationship between epigenomic signals, DNA sequences and their associated regulatory elements. Specifically, we propose to decompose the epigenomic signals and the DNA sequence conditioned on the causal active regulatory elements, and apply an information bottleneck with the Beta distribution to combine their effects while filtering out non-causal components. Our experiments demonstrate that Seq2Exp outperforms existing baselines in gene expression prediction tasks and discovers influential regions compared to commonly used statistical methods for peak detection such as MACS3. The source code is released as part of the AIRS library (https://github.com/divelab/AIRS/).

Decoding the linguistic intricacies of the genome is a crucial problem in biology, and pre-trained foundational models such as DNABERT and Nucleotide Transformer have made significant strides in this area. Existing works have largely hinged on k-mer, fixed-length permutations of A, T, C, and G, as the token of the genome language due to its simplicity. However, we argue that the computation and sample inefficiencies introduced by k-mer tokenization are primary obstacles in developing large genome foundational models. We provide conceptual and empirical insights into genome tokenization, building on which we propose to replace k-mer tokenization with Byte Pair Encoding (BPE), a statistics-based data compression algorithm that constructs tokens by iteratively merging the most frequent co-occurring genome segment in the corpus. We demonstrate that BPE not only overcomes the limitations of k-mer tokenization but also benefits from the computational efficiency of non-overlapping tokenization. Based on these insights, we introduce DNABERT-2, a refined genome foundation model that adapts an efficient tokenizer and employs multiple strategies to overcome input length constraints, reduce time and memory expenditure, and enhance model capability. Furthermore, we identify the absence of a comprehensive and standardized benchmark for genome understanding as another significant impediment to fair comparative analysis. In response, we propose the Genome Understanding Evaluation (GUE), a comprehensive multi-species genome classification dataset that amalgamates 28 distinct datasets across 7 tasks, with input lengths ranging from 70 to 1000. Through comprehensive experiments on the GUE benchmark, we demonstrate that DNABERT-2 achieves comparable performance to the state-of-the-art model with 21 times fewer parameters and approximately 56 times less GPU time in pre-training.

Current pre-training works in natural language generation pay little attention to the problem of exposure bias on downstream tasks. To address this issue, we propose an enhanced multi-flow sequence to sequence pre-training and fine-tuning framework named ERNIE-GEN, which bridges the discrepancy between training and inference with an infilling generation mechanism and a noise-aware generation method. To make generation closer to human writing patterns, this framework introduces a span-by-span generation flow that trains the model to predict semantically-complete spans consecutively rather than predicting word by word. Unlike existing pre-training methods, ERNIE-GEN incorporates multi-granularity target sampling to construct pre-training data, which enhances the correlation between encoder and decoder. Experimental results demonstrate that ERNIE-GEN achieves state-of-the-art results with a much smaller amount of pre-training data and parameters on a range of language generation tasks, including abstractive summarization (Gigaword and CNN/DailyMail), question generation (SQuAD), dialogue generation (Persona-Chat) and generative question answering (CoQA).

Pre-training Transformers has shown promising results on open-domain and domain-specific downstream tasks. However, state-of-the-art Transformers require an unreasonably large amount of pre-training data and compute. In this paper, we propose FPDM (Fast Pre-training Technique using Document Level Metadata), a novel, compute-efficient framework that utilizes Document metadata and Domain-Specific Taxonomy as supervision signals to pre-train transformer encoder on a domain-specific corpus. The main innovation is that during domain-specific pretraining, an open-domain encoder is continually pre-trained using sentence-level embeddings as inputs (to accommodate long documents), however, fine-tuning is done with token-level embeddings as inputs to this encoder. We show that FPDM outperforms several transformer-based baselines in terms of character-level F1 scores and other automated metrics in the Customer Support, Scientific, and Legal Domains, and shows a negligible drop in performance on open-domain benchmarks. Importantly, the novel use of document-level supervision along with sentence-level embedding input for pre-training reduces pre-training compute by around 1,000, 4,500, and 500 times compared to MLM and/or NSP in Customer Support, Scientific, and Legal Domains, respectively. Code and datasets are available at https://bit.ly/FPDMCode.

During times of increasing antibiotic resistance and the spread of infectious diseases like COVID-19, it is important to classify genes related to antibiotic resistance. As natural language processing has advanced with transformer-based language models, many language models that learn characteristics of nucleotide sequences have also emerged. These models show good performance in classifying various features of nucleotide sequences. When classifying nucleotide sequences, not only the sequence itself, but also various background knowledge is utilized. In this study, we use not only a nucleotide sequence-based language model but also a text language model based on PubMed articles to reflect more biological background knowledge in the model. We propose a method to fine-tune the nucleotide sequence language model and the text language model based on various databases of antibiotic resistance genes. We also propose an LLM-based augmentation technique to supplement the data and an ensemble method to effectively combine the two models. We also propose a benchmark for evaluating the model. Our method achieved better performance than the nucleotide sequence language model in the drug resistance class prediction.

The goal of text generation is to make machines express in human language. It is one of the most important yet challenging tasks in natural language processing (NLP). Since 2014, various neural encoder-decoder models pioneered by Seq2Seq have been proposed to achieve the goal by learning to map input text to output text. However, the input text alone often provides limited knowledge to generate the desired output, so the performance of text generation is still far from satisfaction in many real-world scenarios. To address this issue, researchers have considered incorporating various forms of knowledge beyond the input text into the generation models. This research direction is known as knowledge-enhanced text generation. In this survey, we present a comprehensive review of the research on knowledge enhanced text generation over the past five years. The main content includes two parts: (i) general methods and architectures for integrating knowledge into text generation; (ii) specific techniques and applications according to different forms of knowledge data. This survey can have broad audiences, researchers and practitioners, in academia and industry.

Large pretrained models such as GPT-3 have had tremendous impact on modern natural language processing by leveraging self-supervised learning to learn salient representations that can be used to readily finetune on a wide variety of downstream tasks. We investigate the possibility of transferring such advances to molecular machine learning by building a chemical foundation model, ChemBERTa-2, using the language of SMILES. While labeled data for molecular prediction tasks is typically scarce, libraries of SMILES strings are readily available. In this work, we build upon ChemBERTa by optimizing the pretraining process. We compare multi-task and self-supervised pretraining by varying hyperparameters and pretraining dataset size, up to 77M compounds from PubChem. To our knowledge, the 77M set constitutes one of the largest datasets used for molecular pretraining to date. We find that with these pretraining improvements, we are competitive with existing state-of-the-art architectures on the MoleculeNet benchmark suite. We analyze the degree to which improvements in pretraining translate to improvement on downstream tasks.

Pre-trained LLMs have demonstrated substantial capabilities across a range of conventional natural language processing (NLP) tasks, such as summarization and entity recognition. In this paper, we explore the application of LLMs in the generation of high-quality protein sequences. Specifically, we adopt a suite of pre-trained LLMs, including Mistral-7B1, Llama-2-7B2, Llama-3-8B3, and gemma-7B4, to produce valid protein sequences. All of these models are publicly available.5 Unlike previous work in this field, our approach utilizes a relatively small dataset comprising 42,000 distinct human protein sequences. We retrain these models to process protein-related data, ensuring the generation of biologically feasible protein structures. Our findings demonstrate that even with limited data, the adapted models exhibit efficiency comparable to established protein-focused models such as ProGen varieties, ProtGPT2, and ProLLaMA, which were trained on millions of protein sequences. To validate and quantify the performance of our models, we conduct comparative analyses employing standard metrics such as pLDDT, RMSD, TM-score, and REU. Furthermore, we commit to making the trained versions of all four models publicly available, fostering greater transparency and collaboration in the field of computational biology.

Protein language models have shown remarkable success in learning biological information from protein sequences. However, most existing models are limited by either autoencoding or autoregressive pre-training objectives, which makes them struggle to handle protein understanding and generation tasks concurrently. We propose a unified protein language model, xTrimoPGLM, to address these two types of tasks simultaneously through an innovative pre-training framework. Our key technical contribution is an exploration of the compatibility and the potential for joint optimization of the two types of objectives, which has led to a strategy for training xTrimoPGLM at an unprecedented scale of 100 billion parameters and 1 trillion training tokens. Our extensive experiments reveal that 1) xTrimoPGLM significantly outperforms other advanced baselines in 18 protein understanding benchmarks across four categories. The model also facilitates an atomic-resolution view of protein structures, leading to an advanced 3D structural prediction model that surpasses existing language model-based tools. 2) xTrimoPGLM not only can generate de novo protein sequences following the principles of natural ones, but also can perform programmable generation after supervised fine-tuning (SFT) on curated sequences. These results highlight the substantial capability and versatility of xTrimoPGLM in understanding and generating protein sequences, contributing to the evolving landscape of foundation models in protein science.

Offline model-based optimization aims to maximize a black-box objective function with a static dataset of designs and their scores. In this paper, we focus on biological sequence design to maximize some sequence score. A recent approach employs bidirectional learning, combining a forward mapping for exploitation and a backward mapping for constraint, and it relies on the neural tangent kernel (NTK) of an infinitely wide network to build a proxy model. Though effective, the NTK cannot learn features because of its parametrization, and its use prevents the incorporation of powerful pre-trained Language Models (LMs) that can capture the rich biophysical information in millions of biological sequences. We adopt an alternative proxy model, adding a linear head to a pre-trained LM, and propose a linearization scheme. This yields a closed-form loss and also takes into account the biophysical information in the pre-trained LM. In addition, the forward mapping and the backward mapping play different roles and thus deserve different weights during sequence optimization. To achieve this, we train an auxiliary model and leverage its weak supervision signal via a bi-level optimization framework to effectively learn how to balance the two mappings. Further, by extending the framework, we develop the first learning rate adaptation module Adaptive-eta, which is compatible with all gradient-based algorithms for offline model-based optimization. Experimental results on DNA/protein sequence design tasks verify the effectiveness of our algorithm. Our code is available~https://anonymous.4open.science/r/BIB-ICLR2023-Submission/README.md{here.}

In recent years, large language models (LLMs) have achieved state-of-the-art results in various biological sequence analysis tasks, such as sequence classification, structure prediction, and function prediction. Similar to advancements in AI for other scientific fields, deeper research into biological LLMs has begun to focus on using these models to rediscover important existing biological laws or uncover entirely new patterns in biological sequences.This study leverages GPT-like LLMs to utilize language transfer capabilities to rediscover the genetic code rules of the central dogma. In our experimental design, we transformed the central dogma into a binary classification problem of aligning DNA sequences with protein sequences, where positive examples are matching DNA and protein sequences, and negative examples are non-matching pairs.We first trained a GPT-2 model from scratch using a dataset comprising protein sequences, DNA sequences, and sequences from languages such as English and Chinese. Subsequently, we fine-tuned the model using the English similarity judgment dataset from PAWS-X. When tested on a dataset for DNA and protein sequence alignment judgment, the fine-tuned model achieved a classification accuracy of 76%. The study also analyzed factors contributing to this zero-shot capability, including model training stability and types of training data.This research demonstrates that LLMs can, through the transfer of natural language capabilities and solely relying on the analysis of sequences themselves, rediscover the central dogma without prior knowledge of it. This study opens a new door for AI-driven biological research.

Pretrained language models have been used in various natural language processing applications. In the mental health domain, domain-specific language models are pretrained and released, which facilitates the early detection of mental health conditions. Social posts, e.g., on Reddit, are usually long documents. However, there are no domain-specific pretrained models for long-sequence modeling in the mental health domain. This paper conducts domain-specific continued pretraining to capture the long context for mental health. Specifically, we train and release MentalXLNet and MentalLongformer based on XLNet and Longformer. We evaluate the mental health classification performance and the long-range ability of these two domain-specific pretrained models. Our models are released in HuggingFace.

In Information Retrieval, and more generally in Natural Language Processing, adapting models to specific domains is conducted through fine-tuning. Despite the successes achieved by this method and its versatility, the need for human-curated and labeled data makes it impractical to transfer to new tasks, domains, and/or languages when training data doesn't exist. Using the model without training (zero-shot) is another option that however suffers an effectiveness cost, especially in the case of first-stage retrievers. Numerous research directions have emerged to tackle these issues, most of them in the context of adapting to a task or a language. However, the literature is scarcer for domain (or topic) adaptation. In this paper, we address this issue of cross-topic discrepancy for a sparse first-stage retriever by transposing a method initially designed for language adaptation. By leveraging pre-training on the target data to learn domain-specific knowledge, this technique alleviates the need for annotated data and expands the scope of domain adaptation. Despite their relatively good generalization ability, we show that even sparse retrievers can benefit from our simple domain adaptation method.

Effective DNA embedding remains crucial in genomic analysis, particularly in scenarios lacking labeled data for model fine-tuning, despite the significant advancements in genome foundation models. A prime example is metagenomics binning, a critical process in microbiome research that aims to group DNA sequences by their species from a complex mixture of DNA sequences derived from potentially thousands of distinct, often uncharacterized species. To fill the lack of effective DNA embedding models, we introduce DNABERT-S, a genome foundation model that specializes in creating species-aware DNA embeddings. To encourage effective embeddings to error-prone long-read DNA sequences, we introduce Manifold Instance Mixup (MI-Mix), a contrastive objective that mixes the hidden representations of DNA sequences at randomly selected layers and trains the model to recognize and differentiate these mixed proportions at the output layer. We further enhance it with the proposed Curriculum Contrastive Learning (C^2LR) strategy. Empirical results on 18 diverse datasets showed DNABERT-S's remarkable performance. It outperforms the top baseline's performance in 10-shot species classification with just a 2-shot training while doubling the Adjusted Rand Index (ARI) in species clustering and substantially increasing the number of correctly identified species in metagenomics binning. The code, data, and pre-trained model are publicly available at https://github.com/Zhihan1996/DNABERT_S.

In this work we introduce Labrador, a pre-trained Transformer model for laboratory data. Labrador and BERT were pre-trained on a corpus of 100 million lab test results from electronic health records (EHRs) and evaluated on various downstream outcome prediction tasks. Both models demonstrate mastery of the pre-training task but neither consistently outperform XGBoost on downstream supervised tasks. Our ablation studies reveal that transfer learning shows limited effectiveness for BERT and achieves marginal success with Labrador. We explore the reasons for the failure of transfer learning and suggest that the data generating process underlying each patient cannot be characterized sufficiently using labs alone, among other factors. We encourage future work to focus on joint modeling of multiple EHR data categories and to include tree-based baselines in their evaluations.

Pre-training large-scale neural language models on raw texts has made a significant contribution to improving transfer learning in natural language processing (NLP). With the introduction of transformer-based language models, such as bidirectional encoder representations from transformers (BERT), the performance of information extraction from a free text by NLP has significantly improved for both the general domain and medical domain; however, it is difficult to train specific BERT models that perform well for domains in which there are few publicly available databases of high quality and large size. We hypothesized that this problem can be addressed by up-sampling a domain-specific corpus and using it for pre-training with a larger corpus in a balanced manner. Our proposed method consists of a single intervention with one option: simultaneous pre-training after up-sampling and amplified vocabulary. We conducted three experiments and evaluated the resulting products. We confirmed that our Japanese medical BERT outperformed conventional baselines and the other BERT models in terms of the medical document classification task and that our English BERT pre-trained using both the general and medical-domain corpora performed sufficiently well for practical use in terms of the biomedical language understanding evaluation (BLUE) benchmark. Moreover, our enhanced biomedical BERT model, in which clinical notes were not used during pre-training, showed that both the clinical and biomedical scores of the BLUE benchmark were 0.3 points above that of the ablation model trained without our proposed method. Well-balanced pre-training by up-sampling instances derived from a corpus appropriate for the target task allows us to construct a high-performance BERT model.

Large Language Models (LLMs) demonstrate remarkable generalizability across diverse tasks, yet genomic foundation models (GFMs) still require separate finetuning for each downstream application, creating significant overhead as model sizes grow. Moreover, existing GFMs are constrained by rigid output formats, limiting their applicability to various genomic tasks. In this work, we revisit the transformer-based auto-regressive models and introduce Omni-DNA, a family of cross-modal multi-task models ranging from 20 million to 1 billion parameters. Our approach consists of two stages: (i) pretraining on DNA sequences with next token prediction objective, and (ii) expanding the multi-modal task-specific tokens and finetuning for multiple downstream tasks simultaneously. When evaluated on the Nucleotide Transformer and GB benchmarks, Omni-DNA achieves state-of-the-art performance on 18 out of 26 tasks. Through multi-task finetuning, Omni-DNA addresses 10 acetylation and methylation tasks at once, surpassing models trained on each task individually. Finally, we design two complex genomic tasks, DNA2Function and Needle-in-DNA, which map DNA sequences to textual functional descriptions and images, respectively, indicating Omni-DNA's cross-modal capabilities to broaden the scope of genomic applications. All the models are available through https://huggingface.co/collections/zehui127

Given an input sequence (or prefix), modern language models often assign high probabilities to output sequences that are repetitive, incoherent, or irrelevant to the prefix; as such, model-generated text also contains such artifacts. To address these issues we present RankGen, a 1.2B parameter encoder model for English that scores model generations given a prefix. RankGen can be flexibly incorporated as a scoring function in beam search and used to decode from any pretrained language model. We train RankGen using large-scale contrastive learning to map a prefix close to the ground-truth sequence that follows it and far away from two types of negatives: (1) random sequences from the same document as the prefix, and (2) sequences generated from a large language model conditioned on the prefix. Experiments across four different language models (345M-11B parameters) and two domains show that RankGen significantly outperforms decoding algorithms like nucleus, top-k, and typical sampling, as well as contrastive decoding and search, on both automatic metrics (85.0 vs 77.3 MAUVE over nucleus) as well as human evaluations with English writers (74.5% human preference over nucleus sampling). Analysis reveals that RankGen outputs are more relevant to the prefix and improve continuity and coherence compared to baselines. We release our model checkpoints, code, and human preference data with explanations to facilitate future research.

We introduce PRIMERA, a pre-trained model for multi-document representation with a focus on summarization that reduces the need for dataset-specific architectures and large amounts of fine-tuning labeled data. PRIMERA uses our newly proposed pre-training objective designed to teach the model to connect and aggregate information across documents. It also uses efficient encoder-decoder transformers to simplify the processing of concatenated input documents. With extensive experiments on 6 multi-document summarization datasets from 3 different domains on zero-shot, few-shot and full-supervised settings, PRIMERA outperforms current state-of-the-art dataset-specific and pre-trained models on most of these settings with large margins. The code and pre-trained models can be found at https://github.com/allenai/PRIMER.

Recent research in representation learning utilizes large databases of proteins or molecules to acquire knowledge of drug and protein structures through unsupervised learning techniques. These pre-trained representations have proven to significantly enhance the accuracy of subsequent tasks, such as predicting the affinity between drugs and target proteins. In this study, we demonstrate that by incorporating knowledge graphs from diverse sources and modalities into the sequences or SMILES representation, we can further enrich the representation and achieve state-of-the-art results on established benchmark datasets. We provide preprocessed and integrated data obtained from 7 public sources, which encompass over 30M triples. Additionally, we make available the pre-trained models based on this data, along with the reported outcomes of their performance on three widely-used benchmark datasets for drug-target binding affinity prediction found in the Therapeutic Data Commons (TDC) benchmarks. Additionally, we make the source code for training models on benchmark datasets publicly available. Our objective in releasing these pre-trained models, accompanied by clean data for model pretraining and benchmark results, is to encourage research in knowledge-enhanced representation learning.

Recent advances in natural language processing (NLP) can be largely attributed to the advent of pre-trained language models such as BERT and RoBERTa. While these models demonstrate remarkable performance on general datasets, they can struggle in specialized domains such as medicine, where unique domain-specific terminologies, domain-specific abbreviations, and varying document structures are common. This paper explores strategies for adapting these models to domain-specific requirements, primarily through continuous pre-training on domain-specific data. We pre-trained several German medical language models on 2.4B tokens derived from translated public English medical data and 3B tokens of German clinical data. The resulting models were evaluated on various German downstream tasks, including named entity recognition (NER), multi-label classification, and extractive question answering. Our results suggest that models augmented by clinical and translation-based pre-training typically outperform general domain models in medical contexts. We conclude that continuous pre-training has demonstrated the ability to match or even exceed the performance of clinical models trained from scratch. Furthermore, pre-training on clinical data or leveraging translated texts have proven to be reliable methods for domain adaptation in medical NLP tasks.

Recent studies in DNA sequence classification have leveraged sophisticated machine learning techniques, achieving notable accuracy in categorizing complex genomic data. Among these, methods such as k-mer counting have proven effective in distinguishing sequences from varied species like chimpanzees, dogs, and humans, becoming a staple in contemporary genomic research. However, these approaches often demand extensive computational resources, posing a challenge in terms of scalability and efficiency. Addressing this issue, our study introduces a novel adaptation of Jiang et al.'s compressor-based, parameter-free classification method, specifically tailored for DNA sequence analysis. This innovative approach utilizes a variety of compression algorithms, such as Gzip, Brotli, and LZMA, to efficiently process and classify genomic sequences. Not only does this method align with the current state-of-the-art in terms of accuracy, but it also offers a more resource-efficient alternative to traditional machine learning methods. Our comprehensive evaluation demonstrates the proposed method's effectiveness in accurately classifying DNA sequences from multiple species. We present a detailed analysis of the performance of each algorithm used, highlighting the strengths and limitations of our approach in various genomic contexts. Furthermore, we discuss the broader implications of our findings for bioinformatics, particularly in genomic data processing and analysis. The results of our study pave the way for more efficient and scalable DNA sequence classification methods, offering significant potential for advancements in genomic research and applications.

We explore how continued pre-training on domain-specific corpora influences large language models, revealing that training on the raw corpora endows the model with domain knowledge, but drastically hurts its prompting ability for question answering. Taken inspiration from human learning via reading comprehension--practice after reading improves the ability to answer questions based on the learned knowledge--we propose a simple method for transforming raw corpora into reading comprehension texts. Each raw text is enriched with a series of tasks related to its content. Our method, highly scalable and applicable to any pre-training corpora, consistently enhances performance across various tasks in three different domains: biomedicine, finance, and law. Notably, our 7B language model achieves competitive performance with domain-specific models of much larger scales, such as BloombergGPT-50B. Furthermore, we demonstrate that domain-specific reading comprehension texts can improve the model's performance even on general benchmarks, showing the potential to develop a general model across even more domains. Our model, code, and data will be available at https://github.com/microsoft/LMOps.

Breaking domain names such as openresearch into component words open and research is important for applications like Text-to-Speech synthesis and web search. We link this problem to the classic problem of Chinese word segmentation and show the effectiveness of a tagging model based on Recurrent Neural Networks (RNNs) using characters as input. To compensate for the lack of training data, we propose a pre-training method on concatenated entity names in a large knowledge database. Pre-training improves the model by 33% and brings the sequence accuracy to 85%.

Predicting ATP-Protein Binding sites in genes is of great significance in the field of Biology and Medicine. The majority of research in this field has been conducted through time- and resource-intensive 'wet experiments' in laboratories. Over the years, researchers have been investigating computational methods computational methods to accomplish the same goals, utilising the strength of advanced Deep Learning and NLP algorithms. In this paper, we propose to develop methods to classify ATP-Protein binding sites. We conducted various experiments mainly using PSSMs and several word embeddings as features. We used 2D CNNs and LightGBM classifiers as our chief Deep Learning Algorithms. The MP3Vec and BERT models have also been subjected to testing in our study. The outcomes of our experiments demonstrated improvement over the state-of-the-art benchmarks.

Can one inject new concepts into an already trained generative model, while respecting its existing structure and knowledge? We propose a new task - domain expansion - to address this. Given a pretrained generator and novel (but related) domains, we expand the generator to jointly model all domains, old and new, harmoniously. First, we note the generator contains a meaningful, pretrained latent space. Is it possible to minimally perturb this hard-earned representation, while maximally representing the new domains? Interestingly, we find that the latent space offers unused, "dormant" directions, which do not affect the output. This provides an opportunity: By "repurposing" these directions, we can represent new domains without perturbing the original representation. In fact, we find that pretrained generators have the capacity to add several - even hundreds - of new domains! Using our expansion method, one "expanded" model can supersede numerous domain-specific models, without expanding the model size. Additionally, a single expanded generator natively supports smooth transitions between domains, as well as composition of domains. Code and project page available at https://yotamnitzan.github.io/domain-expansion/.

Retrieval-augmented generation (RAG) enhances the question-answering (QA) abilities of large language models (LLMs) by integrating external knowledge. However, adapting general-purpose RAG systems to specialized fields such as science and medicine poses unique challenges due to distribution shifts and limited access to domain-specific data. To tackle this, we propose SimRAG, a self-training approach that equips the LLM with joint capabilities of question answering and question generation for domain adaptation. Our method first fine-tunes the LLM on instruction-following, question-answering, and search-related data. Then, it prompts the same LLM to generate diverse domain-relevant questions from unlabeled corpora, with an additional filtering strategy to retain high-quality synthetic examples. By leveraging these synthetic examples, the LLM can improve their performance on domain-specific RAG tasks. Experiments on 11 datasets, spanning two backbone sizes and three domains, demonstrate that SimRAG outperforms baselines by 1.2\%--8.6\%.

This paper introduces a novel framework for DNA sequence generation, comprising two key components: DiscDiff, a Latent Diffusion Model (LDM) tailored for generating discrete DNA sequences, and Absorb-Escape, a post-training algorithm designed to refine these sequences. Absorb-Escape enhances the realism of the generated sequences by correcting `round errors' inherent in the conversion process between latent and input spaces. Our approach not only sets new standards in DNA sequence generation but also demonstrates superior performance over existing diffusion models, in generating both short and long DNA sequences. Additionally, we introduce EPD-GenDNA, the first comprehensive, multi-species dataset for DNA generation, encompassing 160,000 unique sequences from 15 species. We hope this study will advance the generative modelling of DNA, with potential implications for gene therapy and protein production.

As a fundamental task in computational chemistry, retrosynthesis prediction aims to identify a set of reactants to synthesize a target molecule. Existing template-free approaches only consider the graph structures of the target molecule, which often cannot generalize well to rare reaction types and large molecules. Here, we propose T-Rex, a text-assisted retrosynthesis prediction approach that exploits pre-trained text language models, such as ChatGPT, to assist the generation of reactants. T-Rex first exploits ChatGPT to generate a description for the target molecule and rank candidate reaction centers based both the description and the molecular graph. It then re-ranks these candidates by querying the descriptions for each reactants and examines which group of reactants can best synthesize the target molecule. We observed that T-Rex substantially outperformed graph-based state-of-the-art approaches on two datasets, indicating the effectiveness of considering text information. We further found that T-Rex outperformed the variant that only use ChatGPT-based description without the re-ranking step, demonstrate how our framework outperformed a straightforward integration of ChatGPT and graph information. Collectively, we show that text generated by pre-trained language models can substantially improve retrosynthesis prediction, opening up new avenues for exploiting ChatGPT to advance computational chemistry. And the codes can be found at https://github.com/lauyikfung/T-Rex.

Obtaining text datasets with semantic annotations is an effortful process, yet crucial for supervised training in natural language processsing (NLP). In general, developing and applying new NLP pipelines in domain-specific contexts for tasks often requires custom designed datasets to address NLP tasks in supervised machine learning fashion. When operating in non-English languages for medical data processing, this exposes several minor and major, interconnected problems such as lack of task-matching datasets as well as task-specific pre-trained models. In our work we suggest to leverage pretrained language models for training data acquisition in order to retrieve sufficiently large datasets for training smaller and more efficient models for use-case specific tasks. To demonstrate the effectiveness of your approach, we create a custom dataset which we use to train a medical NER model for German texts, GPTNERMED, yet our method remains language-independent in principle. Our obtained dataset as well as our pre-trained models are publicly available at: https://github.com/frankkramer-lab/GPTNERMED

Pretraining on large-scale, unstructured internet text has enabled language models to acquire a significant amount of world knowledge. However, this knowledge acquisition is data-inefficient -- to learn a given fact, models must be trained on hundreds to thousands of diverse representations of it. This poses a challenge when adapting a pretrained model to a small corpus of domain-specific documents, where each fact may appear rarely or only once. We propose to bridge this gap with synthetic continued pretraining: using the small domain-specific corpus to synthesize a large corpus more amenable to learning, and then performing continued pretraining on the synthesized corpus. We instantiate this proposal with EntiGraph, a synthetic data augmentation algorithm that extracts salient entities from the source documents and then generates diverse text by drawing connections between the sampled entities. Synthetic continued pretraining using EntiGraph enables a language model to answer questions and follow generic instructions related to the source documents without access to them. If instead, the source documents are available at inference time, we show that the knowledge acquired through our approach compounds with retrieval-augmented generation. To better understand these results, we build a simple mathematical model of EntiGraph, and show how synthetic data augmentation can "rearrange" knowledge to enable more data-efficient learning.

Self-supervised learning of speech representations has been a very active research area but most work is focused on a single domain such as read audio books for which there exist large quantities of labeled and unlabeled data. In this paper, we explore more general setups where the domain of the unlabeled data for pre-training data differs from the domain of the labeled data for fine-tuning, which in turn may differ from the test data domain. Our experiments show that using target domain data during pre-training leads to large performance improvements across a variety of setups. On a large-scale competitive setup, we show that pre-training on unlabeled in-domain data reduces the gap between models trained on in-domain and out-of-domain labeled data by 66%-73%. This has obvious practical implications since it is much easier to obtain unlabeled target domain data than labeled data. Moreover, we find that pre-training on multiple domains improves generalization performance on domains not seen during training. Code and models will be made available at https://github.com/pytorch/fairseq.

Traditional drug design faces significant challenges due to inherent chemical and biological complexities, often resulting in high failure rates in clinical trials. Deep learning advancements, particularly generative models, offer potential solutions to these challenges. One promising algorithm is DrugGPT, a transformer-based model, that generates small molecules for input protein sequences. Although promising, it generates both chemically valid and invalid structures and does not incorporate the features of approved drugs, resulting in time-consuming and inefficient drug discovery. To address these issues, we introduce DrugGen, an enhanced model based on the DrugGPT structure. DrugGen is fine-tuned on approved drug-target interactions and optimized with proximal policy optimization. By giving reward feedback from protein-ligand binding affinity prediction using pre-trained transformers (PLAPT) and a customized invalid structure assessor, DrugGen significantly improves performance. Evaluation across multiple targets demonstrated that DrugGen achieves 100% valid structure generation compared to 95.5% with DrugGPT and produced molecules with higher predicted binding affinities (7.22 [6.30-8.07]) compared to DrugGPT (5.81 [4.97-6.63]) while maintaining diversity and novelty. Docking simulations further validate its ability to generate molecules targeting binding sites effectively. For example, in the case of fatty acid-binding protein 5 (FABP5), DrugGen generated molecules with superior docking scores (FABP5/11, -9.537 and FABP5/5, -8.399) compared to the reference molecule (Palmitic acid, -6.177). Beyond lead compound generation, DrugGen also shows potential for drug repositioning and creating novel pharmacophores for existing targets. By producing high-quality small molecules, DrugGen provides a high-performance medium for advancing pharmaceutical research and drug discovery.

Large pre-trained language models have been shown to store factual knowledge in their parameters, and achieve state-of-the-art results when fine-tuned on downstream NLP tasks. However, their ability to access and precisely manipulate knowledge is still limited, and hence on knowledge-intensive tasks, their performance lags behind task-specific architectures. Additionally, providing provenance for their decisions and updating their world knowledge remain open research problems. Pre-trained models with a differentiable access mechanism to explicit non-parametric memory can overcome this issue, but have so far been only investigated for extractive downstream tasks. We explore a general-purpose fine-tuning recipe for retrieval-augmented generation (RAG) -- models which combine pre-trained parametric and non-parametric memory for language generation. We introduce RAG models where the parametric memory is a pre-trained seq2seq model and the non-parametric memory is a dense vector index of Wikipedia, accessed with a pre-trained neural retriever. We compare two RAG formulations, one which conditions on the same retrieved passages across the whole generated sequence, the other can use different passages per token. We fine-tune and evaluate our models on a wide range of knowledge-intensive NLP tasks and set the state-of-the-art on three open domain QA tasks, outperforming parametric seq2seq models and task-specific retrieve-and-extract architectures. For language generation tasks, we find that RAG models generate more specific, diverse and factual language than a state-of-the-art parametric-only seq2seq baseline.

Pre-trained vision-language models (e.g., CLIP) have shown promising zero-shot generalization in many downstream tasks with properly designed text prompts. Instead of relying on hand-engineered prompts, recent works learn prompts using the training data from downstream tasks. While effective, training on domain-specific data reduces a model's generalization capability to unseen new domains. In this work, we propose test-time prompt tuning (TPT), a method that can learn adaptive prompts on the fly with a single test sample. For image classification, TPT optimizes the prompt by minimizing the entropy with confidence selection so that the model has consistent predictions across different augmented views of each test sample. In evaluating generalization to natural distribution shifts, TPT improves the zero-shot top-1 accuracy of CLIP by 3.6% on average, surpassing previous prompt tuning approaches that require additional task-specific training data. In evaluating cross-dataset generalization with unseen categories, TPT performs on par with the state-of-the-art approaches that use additional training data. Project page: https://azshue.github.io/TPT.

In Natural Language Processing (NLP), Machine Reading Comprehension (MRC) is the task of answering a question based on a given context. To handle questions in the medical domain, modern language models such as BioBERT, SciBERT and even ChatGPT are trained on vast amounts of in-domain medical corpora. However, in-domain pre-training is expensive in terms of time and resources. In this paper, we propose a resource-efficient approach for injecting domain knowledge into a model without relying on such domain-specific pre-training. Knowledge graphs are powerful resources for accessing medical information. Building on existing work, we introduce a method using Multi-Layer Perceptrons (MLPs) for aligning and integrating embeddings extracted from medical knowledge graphs with the embedding spaces of pre-trained language models (LMs). The aligned embeddings are fused with open-domain LMs BERT and RoBERTa that are fine-tuned for two MRC tasks, span detection (COVID-QA) and multiple-choice questions (PubMedQA). We compare our method to prior techniques that rely on a vocabulary overlap for embedding alignment and show how our method circumvents this requirement to deliver better performance. On both datasets, our method allows BERT/RoBERTa to either perform on par (occasionally exceeding) with stronger domain-specific models or show improvements in general over prior techniques. With the proposed approach, we signal an alternative method to in-domain pre-training to achieve domain proficiency.

Proteins are essential macromolecules defined by their amino acid sequences, which determine their three-dimensional structures and, consequently, their functions in all living organisms. Therefore, generative protein modeling necessitates a multimodal approach to simultaneously model, understand, and generate both sequences and structures. However, existing methods typically use separate models for each modality, limiting their ability to capture the intricate relationships between sequence and structure. This results in suboptimal performance in tasks that requires joint understanding and generation of both modalities. In this paper, we introduce DPLM-2, a multimodal protein foundation model that extends discrete diffusion protein language model (DPLM) to accommodate both sequences and structures. To enable structural learning with the language model, 3D coordinates are converted to discrete tokens using a lookup-free quantization-based tokenizer. By training on both experimental and high-quality synthetic structures, DPLM-2 learns the joint distribution of sequence and structure, as well as their marginals and conditionals. We also implement an efficient warm-up strategy to exploit the connection between large-scale evolutionary data and structural inductive biases from pre-trained sequence-based protein language models. Empirical evaluation shows that DPLM-2 can simultaneously generate highly compatible amino acid sequences and their corresponding 3D structures eliminating the need for a two-stage generation approach. Moreover, DPLM-2 demonstrates competitive performance in various conditional generation tasks, including folding, inverse folding, and scaffolding with multimodal motif inputs, as well as providing structure-aware representations for predictive tasks.

The parallels between protein sequences and natural language in their sequential structures have inspired the application of large language models (LLMs) to protein understanding. Despite the success of LLMs in NLP, their effectiveness in comprehending protein sequences remains an open question, largely due to the absence of datasets linking protein sequences to descriptive text. Researchers have then attempted to adapt LLMs for protein understanding by integrating a protein sequence encoder with a pre-trained LLM. However, this adaptation raises a fundamental question: "Can LLMs, originally designed for NLP, effectively comprehend protein sequences as a form of language?" Current datasets fall short in addressing this question due to the lack of a direct correlation between protein sequences and corresponding text descriptions, limiting the ability to train and evaluate LLMs for protein understanding effectively. To bridge this gap, we introduce ProteinLMDataset, a dataset specifically designed for further self-supervised pretraining and supervised fine-tuning (SFT) of LLMs to enhance their capability for protein sequence comprehension. Specifically, ProteinLMDataset includes 17.46 billion tokens for pretraining and 893,000 instructions for SFT. Additionally, we present ProteinLMBench, the first benchmark dataset consisting of 944 manually verified multiple-choice questions for assessing the protein understanding capabilities of LLMs. ProteinLMBench incorporates protein-related details and sequences in multiple languages, establishing a new standard for evaluating LLMs' abilities in protein comprehension. The large language model InternLM2-7B, pretrained and fine-tuned on the ProteinLMDataset, outperforms GPT-4 on ProteinLMBench, achieving the highest accuracy score. The dataset and the benchmark are available at https://huggingface.co/datasets/tsynbio/ProteinLMBench.

Advances in natural language processing and large language models have sparked growing interest in modeling DNA, often referred to as the "language of life". However, DNA modeling poses unique challenges. First, it requires the ability to process ultra-long DNA sequences while preserving single-nucleotide resolution, as individual nucleotides play a critical role in DNA function. Second, success in this domain requires excelling at both generative and understanding tasks: generative tasks hold potential for therapeutic and industrial applications, while understanding tasks provide crucial insights into biological mechanisms and diseases. To address these challenges, we propose HybriDNA, a decoder-only DNA language model that incorporates a hybrid Transformer-Mamba2 architecture, seamlessly integrating the strengths of attention mechanisms with selective state-space models. This hybrid design enables HybriDNA to efficiently process DNA sequences up to 131kb in length with single-nucleotide resolution. HybriDNA achieves state-of-the-art performance across 33 DNA understanding datasets curated from the BEND, GUE, and LRB benchmarks, and demonstrates exceptional capability in generating synthetic cis-regulatory elements (CREs) with desired properties. Furthermore, we show that HybriDNA adheres to expected scaling laws, with performance improving consistently as the model scales from 300M to 3B and 7B parameters. These findings underscore HybriDNA's versatility and its potential to advance DNA research and applications, paving the way for innovations in understanding and engineering the "language of life".

Large language models have already demonstrated their formidable capabilities in general domains, ushering in a revolutionary transformation. However, exploring and exploiting the extensive knowledge of these models to comprehend multi-omics biology remains underexplored. To fill this research gap, we first introduce Biology-Instructions, the first large-scale multi-omics biological sequences-related instruction-tuning dataset including DNA, RNA, proteins, and multi-molecules, designed to bridge the gap between large language models (LLMs) and complex biological sequences-related tasks. This dataset can enhance the versatility of LLMs by integrating diverse biological sequenced-based prediction tasks with advanced reasoning capabilities, while maintaining conversational fluency. Additionally, we reveal significant performance limitations in even state-of-the-art LLMs on biological sequence-related multi-omics tasks without specialized pre-training and instruction-tuning. We further develop a strong baseline called ChatMultiOmics with a novel three-stage training pipeline, demonstrating the powerful ability to understand biology by using Biology-Instructions. Biology-Instructions and ChatMultiOmics are publicly available and crucial resources for enabling more effective integration of LLMs with multi-omics sequence analysis.

Although DNA foundation models have advanced the understanding of genomes, they still face significant challenges in the limited scale and diversity of genomic data. This limitation starkly contrasts with the success of natural language foundation models, which thrive on substantially larger scales. Furthermore, genome understanding involves numerous downstream genome annotation tasks with inherent data heterogeneity, thereby necessitating more efficient and robust fine-tuning methods tailored for genomics. Here, we present Lingo: Language prefix fIne-tuning for GenOmes. Unlike DNA foundation models, Lingo strategically leverages natural language foundation models' contextual cues, recalibrating their linguistic knowledge to genomic sequences. Lingo further accommodates numerous, heterogeneous downstream fine-tune tasks by an adaptive rank sampling method that prunes and stochastically reintroduces pruned singular vectors within small computational budgets. Adaptive rank sampling outperformed existing fine-tuning methods on all benchmarked 14 genome understanding tasks, while requiring fewer than 2\% of trainable parameters as genomic-specific adapters. Impressively, applying these adapters on natural language foundation models matched or even exceeded the performance of DNA foundation models. Lingo presents a new paradigm of efficient and scalable genome understanding via genomic-specific adapters on language models.

Pretrained language models such as Bidirectional Encoder Representations from Transformers (BERT) have achieved state-of-the-art performance in natural language processing (NLP) tasks. Recently, BERT has been adapted to the biomedical domain. Despite the effectiveness, these models have hundreds of millions of parameters and are computationally expensive when applied to large-scale NLP applications. We hypothesized that the number of parameters of the original BERT can be dramatically reduced with minor impact on performance. In this study, we present Bioformer, a compact BERT model for biomedical text mining. We pretrained two Bioformer models (named Bioformer8L and Bioformer16L) which reduced the model size by 60% compared to BERTBase. Bioformer uses a biomedical vocabulary and was pre-trained from scratch on PubMed abstracts and PubMed Central full-text articles. We thoroughly evaluated the performance of Bioformer as well as existing biomedical BERT models including BioBERT and PubMedBERT on 15 benchmark datasets of four different biomedical NLP tasks: named entity recognition, relation extraction, question answering and document classification. The results show that with 60% fewer parameters, Bioformer16L is only 0.1% less accurate than PubMedBERT while Bioformer8L is 0.9% less accurate than PubMedBERT. Both Bioformer16L and Bioformer8L outperformed BioBERTBase-v1.1. In addition, Bioformer16L and Bioformer8L are 2-3 fold as fast as PubMedBERT/BioBERTBase-v1.1. Bioformer has been successfully deployed to PubTator Central providing gene annotations over 35 million PubMed abstracts and 5 million PubMed Central full-text articles. We make Bioformer publicly available via https://github.com/WGLab/bioformer, including pre-trained models, datasets, and instructions for downstream use.

The ability to accurately model the fitness landscape of protein sequences is critical to a wide range of applications, from quantifying the effects of human variants on disease likelihood, to predicting immune-escape mutations in viruses and designing novel biotherapeutic proteins. Deep generative models of protein sequences trained on multiple sequence alignments have been the most successful approaches so far to address these tasks. The performance of these methods is however contingent on the availability of sufficiently deep and diverse alignments for reliable training. Their potential scope is thus limited by the fact many protein families are hard, if not impossible, to align. Large language models trained on massive quantities of non-aligned protein sequences from diverse families address these problems and show potential to eventually bridge the performance gap. We introduce Tranception, a novel transformer architecture leveraging autoregressive predictions and retrieval of homologous sequences at inference to achieve state-of-the-art fitness prediction performance. Given its markedly higher performance on multiple mutants, robustness to shallow alignments and ability to score indels, our approach offers significant gain of scope over existing approaches. To enable more rigorous model testing across a broader range of protein families, we develop ProteinGym -- an extensive set of multiplexed assays of variant effects, substantially increasing both the number and diversity of assays compared to existing benchmarks.

Generative machine learning models are increasingly being used to design novel proteins for therapeutic and biotechnological applications. However, the current methods mostly focus on the design of proteins with a fixed backbone structure, which leads to their limited ability to account for protein flexibility, one of the crucial properties for protein function. Learning to engineer protein flexibility is problematic because the available data are scarce, heterogeneous, and costly to obtain using computational as well as experimental methods. Our contributions to address this problem are three-fold. First, we comprehensively compare methods for quantifying protein flexibility and identify data relevant to learning. Second, we design and train flexibility predictors utilizing sequential or both sequential and structural information on the input. We overcome the data scarcity issue by leveraging a pre-trained protein language model. Third, we introduce a method for fine-tuning a protein inverse folding model to steer it toward desired flexibility in specified regions. We demonstrate that our method Flexpert-Design enables guidance of inverse folding models toward increased flexibility. This opens up new possibilities for protein flexibility engineering and the development of proteins with enhanced biological activities.

Generative models have become widely used in biomedical entity linking (BioEL) due to their excellent performance and efficient memory usage. However, these models are usually trained only with positive samples--entities that match the input mention's identifier--and do not explicitly learn from hard negative samples, which are entities that look similar but have different meanings. To address this limitation, we introduce ANGEL (Learning from Negative Samples in Generative Biomedical Entity Linking), the first framework that trains generative BioEL models using negative samples. Specifically, a generative model is initially trained to generate positive samples from the knowledge base for given input entities. Subsequently, both correct and incorrect outputs are gathered from the model's top-k predictions. The model is then updated to prioritize the correct predictions through direct preference optimization. Our models fine-tuned with ANGEL outperform the previous best baseline models by up to an average top-1 accuracy of 1.4% on five benchmarks. When incorporating our framework into pre-training, the performance improvement further increases to 1.7%, demonstrating its effectiveness in both the pre-training and fine-tuning stages. Our code is available at https://github.com/dmis-lab/ANGEL.

Recent studies have demonstrated the strong empirical performance of diffusion models on discrete sequences across domains from natural language to biological sequence generation. For example, in the protein inverse folding task, conditional diffusion models have achieved impressive results in generating natural-like sequences that fold back into the original structure. However, practical design tasks often require not only modeling a conditional distribution but also optimizing specific task objectives. For instance, we may prefer protein sequences with high stability. To address this, we consider the scenario where we have pre-trained discrete diffusion models that can generate natural-like sequences, as well as reward models that map sequences to task objectives. We then formulate the reward maximization problem within discrete diffusion models, analogous to reinforcement learning (RL), while minimizing the KL divergence against pretrained diffusion models to preserve naturalness. To solve this RL problem, we propose a novel algorithm, DRAKES, that enables direct backpropagation of rewards through entire trajectories generated by diffusion models, by making the originally non-differentiable trajectories differentiable using the Gumbel-Softmax trick. Our theoretical analysis indicates that our approach can generate sequences that are both natural-like and yield high rewards. While similar tasks have been recently explored in diffusion models for continuous domains, our work addresses unique algorithmic and theoretical challenges specific to discrete diffusion models, which arise from their foundation in continuous-time Markov chains rather than Brownian motion. Finally, we demonstrate the effectiveness of DRAKES in generating DNA and protein sequences that optimize enhancer activity and protein stability, respectively, important tasks for gene therapies and protein-based therapeutics.

The question-answering system for Life science research, which is characterized by the rapid pace of discovery, evolving insights, and complex interactions among knowledge entities, presents unique challenges in maintaining a comprehensive knowledge warehouse and accurate information retrieval. To address these issues, we introduce BioRAG, a novel Retrieval-Augmented Generation (RAG) with the Large Language Models (LLMs) framework. Our approach starts with parsing, indexing, and segmenting an extensive collection of 22 million scientific papers as the basic knowledge, followed by training a specialized embedding model tailored to this domain. Additionally, we enhance the vector retrieval process by incorporating a domain-specific knowledge hierarchy, which aids in modeling the intricate interrelationships among each query and context. For queries requiring the most current information, BioRAG deconstructs the question and employs an iterative retrieval process incorporated with the search engine for step-by-step reasoning. Rigorous experiments have demonstrated that our model outperforms fine-tuned LLM, LLM with search engines, and other scientific RAG frameworks across multiple life science question-answering tasks.

Gene set knowledge discovery is essential for advancing human functional genomics. Recent studies have shown promising performance by harnessing the power of Large Language Models (LLMs) on this task. Nonetheless, their results are subject to several limitations common in LLMs such as hallucinations. In response, we present GeneAgent, a first-of-its-kind language agent featuring self-verification capability. It autonomously interacts with various biological databases and leverages relevant domain knowledge to improve accuracy and reduce hallucination occurrences. Benchmarking on 1,106 gene sets from different sources, GeneAgent consistently outperforms standard GPT-4 by a significant margin. Moreover, a detailed manual review confirms the effectiveness of the self-verification module in minimizing hallucinations and generating more reliable analytical narratives. To demonstrate its practical utility, we apply GeneAgent to seven novel gene sets derived from mouse B2905 melanoma cell lines, with expert evaluations showing that GeneAgent offers novel insights into gene functions and subsequently expedites knowledge discovery.

Recent research trends in computational biology have increasingly focused on integrating text and bio-entity modeling, especially in the context of molecules and proteins. However, previous efforts like BioT5 faced challenges in generalizing across diverse tasks and lacked a nuanced understanding of molecular structures, particularly in their textual representations (e.g., IUPAC). This paper introduces BioT5+, an extension of the BioT5 framework, tailored to enhance biological research and drug discovery. BioT5+ incorporates several novel features: integration of IUPAC names for molecular understanding, inclusion of extensive bio-text and molecule data from sources like bioRxiv and PubChem, the multi-task instruction tuning for generality across tasks, and a novel numerical tokenization technique for improved processing of numerical data. These enhancements allow BioT5+ to bridge the gap between molecular representations and their textual descriptions, providing a more holistic understanding of biological entities, and largely improving the grounded reasoning of bio-text and bio-sequences. The model is pre-trained and fine-tuned with a large number of experiments, including 3 types of problems (classification, regression, generation), 15 kinds of tasks, and 21 total benchmark datasets, demonstrating the remarkable performance and state-of-the-art results in most cases. BioT5+ stands out for its ability to capture intricate relationships in biological data, thereby contributing significantly to bioinformatics and computational biology. Our code is available at https://github.com/QizhiPei/BioT5.

Many recent machine learning tasks focus to develop models that can generalize to unseen distributions. Domain generalization (DG) has become one of the key topics in various fields. Several literatures show that DG can be arbitrarily hard without exploiting target domain information. To address this issue, test-time adaptive (TTA) methods are proposed. Existing TTA methods require offline target data or extra sophisticated optimization procedures during the inference stage. In this work, we adopt Non-Parametric Classifier to perform the test-time Adaptation (AdaNPC). In particular, we construct a memory that contains the feature and label pairs from training domains. During inference, given a test instance, AdaNPC first recalls K closed samples from the memory to vote for the prediction, and then the test feature and predicted label are added to the memory. In this way, the sample distribution in the memory can be gradually changed from the training distribution towards the test distribution with very little extra computation cost. We theoretically justify the rationality behind the proposed method. Besides, we test our model on extensive numerical experiments. AdaNPC significantly outperforms competitive baselines on various DG benchmarks. In particular, when the adaptation target is a series of domains, the adaptation accuracy of AdaNPC is 50% higher than advanced TTA methods. The code is available at https://github.com/yfzhang114/AdaNPC.

Antibodies comprise the most versatile class of binding molecules, with numerous applications in biomedicine. Computational design of antibodies involves generating novel and diverse sequences, while maintaining structural consistency. Unique to antibodies, designing the complementarity-determining region (CDR), which determines the antigen binding affinity and specificity, creates its own unique challenges. Recent deep learning models have shown impressive results, however the limited number of known antibody sequence/structure pairs frequently leads to degraded performance, particularly lacking diversity in the generated sequences. In our work we address this challenge by leveraging Model Reprogramming (MR), which repurposes pretrained models on a source language to adapt to the tasks that are in a different language and have scarce data - where it may be difficult to train a high-performing model from scratch or effectively fine-tune an existing pre-trained model on the specific task. Specifically, we introduce ReprogBert in which a pretrained English language model is repurposed for protein sequence infilling - thus considers cross-language adaptation using less data. Results on antibody design benchmarks show that our model on low-resourced antibody sequence dataset provides highly diverse CDR sequences, up to more than a two-fold increase of diversity over the baselines, without losing structural integrity and naturalness. The generated sequences also demonstrate enhanced antigen binding specificity and virus neutralization ability. Code is available at https://github.com/IBM/ReprogBERT

Molecule generation with desired properties has grown immensely in popularity by disruptively changing the way scientists design molecular structures and providing support for chemical and materials design. However, despite the promising outcome, previous machine learning-based deep generative models suffer from a reliance on complex, task-specific fine-tuning, limited dimensional latent spaces, or the quality of expert rules. In this work, we propose MolGen, a pre-trained molecular language model that effectively learns and shares knowledge across multiple generation tasks and domains. Specifically, we pre-train MolGen with the chemical language SELFIES on more than 100 million unlabelled molecules. We further propose multi-task molecular prefix tuning across several molecular generation tasks and different molecular domains (synthetic & natural products) with a self-feedback mechanism. Extensive experiments show that MolGen can obtain superior performances on well-known molecular generation benchmark datasets. The further analysis illustrates that MolGen can accurately capture the distribution of molecules, implicitly learn their structural characteristics, and efficiently explore the chemical space with the guidance of multi-task molecular prefix tuning. Codes, datasets, and the pre-trained model will be available in https://github.com/zjunlp/MolGen.

Despite the significant advancements in text-to-image (T2I) generative models, users often face a trial-and-error challenge in practical scenarios. This challenge arises from the complexity and uncertainty of tedious steps such as crafting suitable prompts, selecting appropriate models, and configuring specific arguments, making users resort to labor-intensive attempts for desired images. This paper proposes Automatic T2I generation, which aims to automate these tedious steps, allowing users to simply describe their needs in a freestyle chatting way. To systematically study this problem, we first introduce ChatGenBench, a novel benchmark designed for Automatic T2I. It features high-quality paired data with diverse freestyle inputs, enabling comprehensive evaluation of automatic T2I models across all steps. Additionally, recognizing Automatic T2I as a complex multi-step reasoning task, we propose ChatGen-Evo, a multi-stage evolution strategy that progressively equips models with essential automation skills. Through extensive evaluation across step-wise accuracy and image quality, ChatGen-Evo significantly enhances performance over various baselines. Our evaluation also uncovers valuable insights for advancing automatic T2I. All our data, code, and models will be available in https://chengyou-jia.github.io/ChatGen-Home

I present Astro-HEP-BERT, a transformer-based language model specifically designed for generating contextualized word embeddings (CWEs) to study the meanings of concepts in astrophysics and high-energy physics. Built on a general pretrained BERT model, Astro-HEP-BERT underwent further training over three epochs using the Astro-HEP Corpus, a dataset I curated from 21.84 million paragraphs extracted from more than 600,000 scholarly articles on arXiv, all belonging to at least one of these two scientific domains. The project demonstrates both the effectiveness and feasibility of adapting a bidirectional transformer for applications in the history, philosophy, and sociology of science (HPSS). The entire training process was conducted using freely available code, pretrained weights, and text inputs, completed on a single MacBook Pro Laptop (M2/96GB). Preliminary evaluations indicate that Astro-HEP-BERT's CWEs perform comparably to domain-adapted BERT models trained from scratch on larger datasets for domain-specific word sense disambiguation and induction and related semantic change analyses. This suggests that retraining general language models for specific scientific domains can be a cost-effective and efficient strategy for HPSS researchers, enabling high performance without the need for extensive training from scratch.

In recent years, pre-trained language models (PLMs) achieve the best performance on a wide range of natural language processing (NLP) tasks. While the first models were trained on general domain data, specialized ones have emerged to more effectively treat specific domains. In this paper, we propose an original study of PLMs in the medical domain on French language. We compare, for the first time, the performance of PLMs trained on both public data from the web and private data from healthcare establishments. We also evaluate different learning strategies on a set of biomedical tasks. In particular, we show that we can take advantage of already existing biomedical PLMs in a foreign language by further pre-train it on our targeted data. Finally, we release the first specialized PLMs for the biomedical field in French, called DrBERT, as well as the largest corpus of medical data under free license on which these models are trained.

Protein language models are a powerful tool for learning protein representations through pre-training on vast protein sequence datasets. However, traditional protein language models lack explicit structural supervision, despite its relevance to protein function. To address this issue, we introduce the integration of remote homology detection to distill structural information into protein language models without requiring explicit protein structures as input. We evaluate the impact of this structure-informed training on downstream protein function prediction tasks. Experimental results reveal consistent improvements in function annotation accuracy for EC number and GO term prediction. Performance on mutant datasets, however, varies based on the relationship between targeted properties and protein structures. This underscores the importance of considering this relationship when applying structure-aware training to protein function prediction tasks. Code and model weights are available at https://github.com/DeepGraphLearning/esm-s.

Large language models, particularly GPT-3, are able to produce high quality summaries of general domain news articles in few- and zero-shot settings. However, it is unclear if such models are similarly capable in more specialized, high-stakes domains such as biomedicine. In this paper, we enlist domain experts (individuals with medical training) to evaluate summaries of biomedical articles generated by GPT-3, given zero supervision. We consider both single- and multi-document settings. In the former, GPT-3 is tasked with generating regular and plain-language summaries of articles describing randomized controlled trials; in the latter, we assess the degree to which GPT-3 is able to synthesize evidence reported across a collection of articles. We design an annotation scheme for evaluating model outputs, with an emphasis on assessing the factual accuracy of generated summaries. We find that while GPT-3 is able to summarize and simplify single biomedical articles faithfully, it struggles to provide accurate aggregations of findings over multiple documents. We release all data and annotations used in this work.

Proteins power a vast array of functional processes in living cells. The capability to create new proteins with designed structures and functions would thus enable the engineering of cellular behavior and development of protein-based therapeutics and materials. Structure-based protein design aims to find structures that are designable (can be realized by a protein sequence), novel (have dissimilar geometry from natural proteins), and diverse (span a wide range of geometries). While advances in protein structure prediction have made it possible to predict structures of novel protein sequences, the combinatorially large space of sequences and structures limits the practicality of search-based methods. Generative models provide a compelling alternative, by implicitly learning the low-dimensional structure of complex data distributions. Here, we leverage recent advances in denoising diffusion probabilistic models and equivariant neural networks to develop Genie, a generative model of protein structures that performs discrete-time diffusion using a cloud of oriented reference frames in 3D space. Through in silico evaluations, we demonstrate that Genie generates protein backbones that are more designable, novel, and diverse than existing models. This indicates that Genie is capturing key aspects of the distribution of protein structure space and facilitates protein design with high success rates. Code for generating new proteins and training new versions of Genie is available at https://github.com/aqlaboratory/genie.

Pretraining datasets for large language models (LLMs) have grown to trillions of tokens composed of large amounts of CommonCrawl (CC) web scrape along with smaller, domain-specific datasets. It is expensive to understand the impact of these domain-specific datasets on model capabilities as training at large FLOP scales is required to reveal significant changes to difficult and emergent benchmarks. Given the increasing cost of experimenting with pretraining data, how does one determine the optimal balance between the diversity in general web scrapes and the information density of domain specific data? In this work, we show how to leverage the smaller domain specific datasets by upsampling them relative to CC at the end of training to drive performance improvements on difficult benchmarks. This simple technique allows us to improve up to 6.90 pp on MMLU, 8.26 pp on GSM8K, and 6.17 pp on HumanEval relative to the base data mix for a 7B model trained for 1 trillion (T) tokens, thus rivaling Llama-2 (7B)x2014a model trained for twice as long. We experiment with ablating the duration of domain upsampling from 5% to 30% of training and find that 10% to 20% percent is optimal for navigating the tradeoff between general language modeling capabilities and targeted benchmarks. We also use domain upsampling to characterize at scale the utility of individual datasets for improving various benchmarks by removing them during this final phase of training. This tool opens up the ability to experiment with the impact of different pretraining datasets at scale, but at an order of magnitude lower cost compared to full pretraining runs.

The rapid expansion of genomic sequence data calls for new methods to achieve robust sequence representations. Existing techniques often neglect intricate structural details, emphasizing mainly contextual information. To address this, we developed k-mer embeddings that merge contextual and structural string information by enhancing De Bruijn graphs with structural similarity connections. Subsequently, we crafted a self-supervised method based on Contrastive Learning that employs a heterogeneous Graph Convolutional Network encoder and constructs positive pairs based on node similarities. Our embeddings consistently outperform prior techniques for Edit Distance Approximation and Closest String Retrieval tasks.

Keyphrase Generation (KPG) is a longstanding task in NLP with widespread applications. The advent of sequence-to-sequence (seq2seq) pre-trained language models (PLMs) has ushered in a transformative era for KPG, yielding promising performance improvements. However, many design decisions remain unexplored and are often made arbitrarily. This paper undertakes a systematic analysis of the influence of model selection and decoding strategies on PLM-based KPG. We begin by elucidating why seq2seq PLMs are apt for KPG, anchored by an attention-driven hypothesis. We then establish that conventional wisdom for selecting seq2seq PLMs lacks depth: (1) merely increasing model size or performing task-specific adaptation is not parameter-efficient; (2) although combining in-domain pre-training with task adaptation benefits KPG, it does partially hinder generalization. Regarding decoding, we demonstrate that while greedy search achieves strong F1 scores, it lags in recall compared with sampling-based methods. Based on these insights, we propose DeSel, a likelihood-based decode-select algorithm for seq2seq PLMs. DeSel improves greedy search by an average of 4.7% semantic F1 across five datasets. Our collective findings pave the way for deeper future investigations into PLM-based KPG.

Recently, reading comprehension models achieved near-human performance on large-scale datasets such as SQuAD, CoQA, MS Macro, RACE, etc. This is largely due to the release of pre-trained contextualized representations such as BERT and ELMo, which can be fine-tuned for the target task. Despite those advances and the creation of more challenging datasets, most of the work is still done for English. Here, we study the effectiveness of multilingual BERT fine-tuned on large-scale English datasets for reading comprehension (e.g., for RACE), and we apply it to Bulgarian multiple-choice reading comprehension. We propose a new dataset containing 2,221 questions from matriculation exams for twelfth grade in various subjects -history, biology, geography and philosophy-, and 412 additional questions from online quizzes in history. While the quiz authors gave no relevant context, we incorporate knowledge from Wikipedia, retrieving documents matching the combination of question + each answer option. Moreover, we experiment with different indexing and pre-training strategies. The evaluation results show accuracy of 42.23%, which is well above the baseline of 24.89%.

Recently, pre-trained models have achieved state-of-the-art results in various language understanding tasks, which indicates that pre-training on large-scale corpora may play a crucial role in natural language processing. Current pre-training procedures usually focus on training the model with several simple tasks to grasp the co-occurrence of words or sentences. However, besides co-occurring, there exists other valuable lexical, syntactic and semantic information in training corpora, such as named entity, semantic closeness and discourse relations. In order to extract to the fullest extent, the lexical, syntactic and semantic information from training corpora, we propose a continual pre-training framework named ERNIE 2.0 which builds and learns incrementally pre-training tasks through constant multi-task learning. Experimental results demonstrate that ERNIE 2.0 outperforms BERT and XLNet on 16 tasks including English tasks on GLUE benchmarks and several common tasks in Chinese. The source codes and pre-trained models have been released at https://github.com/PaddlePaddle/ERNIE.

Using language models (LMs) pre-trained in a self-supervised setting on large corpora and then fine-tuning for a downstream task has helped to deal with the problem of limited label data for supervised learning tasks such as Named Entity Recognition (NER). Recent research in biomedical language processing has offered a number of biomedical LMs pre-trained using different methods and techniques that advance results on many BioNLP tasks, including NER. However, there is still a lack of a comprehensive comparison of pre-training approaches that would work more optimally in the biomedical domain. This paper aims to investigate different pre-training methods, such as pre-training the biomedical LM from scratch and pre-training it in a continued fashion. We compare existing methods with our proposed pre-training method of initializing weights for new tokens by distilling existing weights from the BERT model inside the context where the tokens were found. The method helps to speed up the pre-training stage and improve performance on NER. In addition, we compare how masking rate, corruption strategy, and masking strategies impact the performance of the biomedical LM. Finally, using the insights from our experiments, we introduce a new biomedical LM (BIOptimus), which is pre-trained using Curriculum Learning (CL) and contextualized weight distillation method. Our model sets new states of the art on several biomedical Named Entity Recognition (NER) tasks. We release our code and all pre-trained models

In this paper, we generalize text infilling (e.g., masked language models) by proposing Sequence Span Rewriting (SSR) as a self-supervised sequence-to-sequence (seq2seq) pre-training objective. SSR provides more fine-grained learning signals for text representations by supervising the model to rewrite imperfect spans to ground truth, and it is more consistent than text infilling with many downstream seq2seq tasks that rewrite a source sentences into a target sentence. Our experiments with T5 models on various seq2seq tasks show that SSR can substantially improve seq2seq pre-training. Moreover, we observe SSR is especially helpful to improve pre-training a small-size seq2seq model with a powerful imperfect span generator, which indicates a new perspective of transferring knowledge from a large model to a smaller model for seq2seq pre-training.

Contrastive Language-Image Pre-training (CLIP) on large-scale image-caption datasets learns representations that can achieve remarkable zero-shot generalization. However, such models require a massive amount of pre-training data. Improving the quality of the pre-training data has been shown to be much more effective in improving CLIP's performance than increasing its volume. Nevertheless, finding small subsets of training data that provably generalize the best has remained an open question. In this work, we propose the first theoretically rigorous data selection method for CLIP. We show that subsets that closely preserve the cross-covariance of the images and captions of the full data provably achieve a superior generalization performance. Our extensive experiments on ConceptualCaptions3M and ConceptualCaptions12M demonstrate that subsets found by \method\ achieve over 2.7x and 1.4x the accuracy of the next best baseline on ImageNet and its shifted versions. Moreover, we show that our subsets obtain 1.5x the average accuracy across 11 downstream datasets, of the next best baseline. The code is available at: https://github.com/BigML-CS-UCLA/clipcov-data-efficient-clip.

Text embedding models play a crucial role in natural language processing, particularly in information retrieval, and their importance is further highlighted with the recent utilization of RAG (Retrieval- Augmented Generation). This study presents an efficient fine-tuning methodology encompassing data selection, loss function, and model architecture to enhance the information retrieval performance of pre-trained text embedding models. In particular, this study proposes a novel Contrastive Learning Penalty function that overcomes the limitations of existing Contrastive Learning. The proposed methodology achieves significant performance improvements over existing methods in document retrieval tasks. This study is expected to contribute to improving the performance of information retrieval systems through fine-tuning of text embedding models. The code for this study can be found at https://github.com/CreaLabs/Enhanced-BGE-M3-with-CLP-and-MoE, and the best-performing model can be found at https://huggingface.co/CreaLabs.

Training and evaluating language models increasingly requires the construction of meta-datasets --diverse collections of curated data with clear provenance. Natural language prompting has recently lead to improved zero-shot generalization by transforming existing, supervised datasets into a diversity of novel pretraining tasks, highlighting the benefits of meta-dataset curation. While successful in general-domain text, translating these data-centric approaches to biomedical language modeling remains challenging, as labeled biomedical datasets are significantly underrepresented in popular data hubs. To address this challenge, we introduce BigBIO a community library of 126+ biomedical NLP datasets, currently covering 12 task categories and 10+ languages. BigBIO facilitates reproducible meta-dataset curation via programmatic access to datasets and their metadata, and is compatible with current platforms for prompt engineering and end-to-end few/zero shot language model evaluation. We discuss our process for task schema harmonization, data auditing, contribution guidelines, and outline two illustrative use cases: zero-shot evaluation of biomedical prompts and large-scale, multi-task learning. BigBIO is an ongoing community effort and is available at https://github.com/bigscience-workshop/biomedical

Much recent research on information retrieval has focused on how to transfer from one task (typically with abundant supervised data) to various other tasks where supervision is limited, with the implicit assumption that it is possible to generalize from one task to all the rest. However, this overlooks the fact that there are many diverse and unique retrieval tasks, each targeting different search intents, queries, and search domains. In this paper, we suggest to work on Few-shot Dense Retrieval, a setting where each task comes with a short description and a few examples. To amplify the power of a few examples, we propose Prompt-base Query Generation for Retriever (Promptagator), which leverages large language models (LLM) as a few-shot query generator, and creates task-specific retrievers based on the generated data. Powered by LLM's generalization ability, Promptagator makes it possible to create task-specific end-to-end retrievers solely based on a few examples {without} using Natural Questions or MS MARCO to train %question generators or dual encoders. Surprisingly, LLM prompting with no more than 8 examples allows dual encoders to outperform heavily engineered models trained on MS MARCO like ColBERT v2 by more than 1.2 nDCG on average on 11 retrieval sets. Further training standard-size re-rankers using the same generated data yields another 5.0 point nDCG improvement. Our studies determine that query generation can be far more effective than previously observed, especially when a small amount of task-specific knowledge is given.

While self-supervised learning has made rapid advances in natural language processing, it remains unclear when researchers should engage in resource-intensive domain-specific pretraining (domain pretraining). The law, puzzlingly, has yielded few documented instances of substantial gains to domain pretraining in spite of the fact that legal language is widely seen to be unique. We hypothesize that these existing results stem from the fact that existing legal NLP tasks are too easy and fail to meet conditions for when domain pretraining can help. To address this, we first present CaseHOLD (Case Holdings On Legal Decisions), a new dataset comprised of over 53,000+ multiple choice questions to identify the relevant holding of a cited case. This dataset presents a fundamental task to lawyers and is both legally meaningful and difficult from an NLP perspective (F1 of 0.4 with a BiLSTM baseline). Second, we assess performance gains on CaseHOLD and existing legal NLP datasets. While a Transformer architecture (BERT) pretrained on a general corpus (Google Books and Wikipedia) improves performance, domain pretraining (using corpus of approximately 3.5M decisions across all courts in the U.S. that is larger than BERT's) with a custom legal vocabulary exhibits the most substantial performance gains with CaseHOLD (gain of 7.2% on F1, representing a 12% improvement on BERT) and consistent performance gains across two other legal tasks. Third, we show that domain pretraining may be warranted when the task exhibits sufficient similarity to the pretraining corpus: the level of performance increase in three legal tasks was directly tied to the domain specificity of the task. Our findings inform when researchers should engage resource-intensive pretraining and show that Transformer-based architectures, too, learn embeddings suggestive of distinct legal language.

RNA is a vital biomolecule with numerous roles and functions within cells, and interest in targeting it for therapeutic purposes has grown significantly in recent years. However, fully understanding and predicting RNA behavior, particularly for applications in drug discovery, remains a challenge due to the complexity of RNA structures and interactions. While foundational models in biology have demonstrated success in modeling several biomolecules, especially proteins, achieving similar breakthroughs for RNA has proven more difficult. Current RNA models have yet to match the performance observed in the protein domain, leaving an important gap in computational biology. In this work, we present ChaRNABERT, a suite of sample and parameter-efficient RNA foundational models, that through a learnable tokenization process, are able to reach state-of-the-art performance on several tasks in established benchmarks. We extend its testing in relevant downstream tasks such as RNA-protein and aptamer-protein interaction prediction. Weights and inference code for ChaRNABERT-8M will be provided for academic research use. The other models will be available upon request.

Pretraining is the preliminary and fundamental step in developing capable language models (LM). Despite this, pretraining data design is critically under-documented and often guided by empirically unsupported intuitions. To address this, we pretrain 28 1.5B parameter decoder-only models, training on data curated (1) at different times, (2) with varying toxicity and quality filters, and (3) with different domain compositions. First, we quantify the effect of pretraining data age. A temporal shift between evaluation data and pretraining data leads to performance degradation, which is not overcome by finetuning. Second, we explore the effect of quality and toxicity filters, showing a trade-off between performance on standard benchmarks and risk of toxic generations. Our findings indicate there does not exist a one-size-fits-all solution to filtering training data. We also find that the effects of different types of filtering are not predictable from text domain characteristics. Lastly, we empirically validate that the inclusion of heterogeneous data sources, like books and web, is broadly beneficial and warrants greater prioritization. These findings constitute the largest set of experiments to validate, quantify, and expose many undocumented intuitions about text pretraining, which we hope will help support more informed data-centric decisions in LM development.

The ever-growing diversity of pre-training text corpora has equipped language models with generalization capabilities across various downstream tasks. However, such diverse datasets are often too large for academic budgets; hence, most research on Transformer architectures, training procedures, optimizers, etc. gets conducted on smaller, homogeneous datasets. To this end, we present The MiniPile Challenge, where one pre-trains a language model on a diverse text corpus containing at most 1M documents. MiniPile is a 6GB subset of the deduplicated 825GB The Pile corpus. To curate MiniPile, we perform a simple, three-step data filtering process: we (1) infer embeddings for all documents of the Pile, (2) cluster the embedding space using k-means, and (3) filter out low-quality clusters. To verify MiniPile's suitability for language model pre-training, we use it to pre-train a BERT and T5 model, yielding a performance drop of only 1.9%/2.5% on the GLUE and SNI benchmarks compared to the original pre-trained checkpoints trained on 2.6x/745x the amount of data. MiniPile is available at https://huggingface.co/datasets/JeanKaddour/minipile.

Data of sequential nature arise in many application domains in forms of, e.g. textual data, DNA sequences, and software execution traces. Different research disciplines have developed methods to learn sequence models from such datasets: (i) in the machine learning field methods such as (hidden) Markov models and recurrent neural networks have been developed and successfully applied to a wide-range of tasks, (ii) in process mining process discovery techniques aim to generate human-interpretable descriptive models, and (iii) in the grammar inference field the focus is on finding descriptive models in the form of formal grammars. Despite their different focuses, these fields share a common goal - learning a model that accurately describes the behavior in the underlying data. Those sequence models are generative, i.e, they can predict what elements are likely to occur after a given unfinished sequence. So far, these fields have developed mainly in isolation from each other and no comparison exists. This paper presents an interdisciplinary experimental evaluation that compares sequence modeling techniques on the task of next-element prediction on four real-life sequence datasets. The results indicate that machine learning techniques that generally have no aim at interpretability in terms of accuracy outperform techniques from the process mining and grammar inference fields that aim to yield interpretable models.

In this paper, we introduce a novel dIffusion language modEl pre-training framework for text generation, which we call GENIE. GENIE is a large-scale pretrained diffusion language model that consists of an encoder and a diffusion-based decoder, which can generate text by gradually transforming a random noise sequence into a coherent text sequence. To pre-train GENIE on a large-scale language corpus, we design a new continuous paragraph denoise objective, which encourages the diffusion-decoder to reconstruct a clean text paragraph from a corrupted version, while preserving the semantic and syntactic coherence. We evaluate GENIE on four downstream text generation benchmarks, namely XSum, CNN/DailyMail, Gigaword, and CommonGen. Our experimental results show that GENIE achieves comparable performance with the state-of-the-art autoregressive models on these benchmarks, and generates more diverse text samples. The code and models of GENIE are available at https://github.com/microsoft/ProphetNet/tree/master/GENIE.

The sparsity of labelled data is an obstacle to the development of Relation Extraction models and the completion of databases in various biomedical areas. While being of high interest in drug-discovery, the natural-products literature, reporting the identification of potential bioactive compounds from organisms, is a concrete example of such an overlooked topic. To mark the start of this new task, we created the first curated evaluation dataset and extracted literature items from the LOTUS database to build training sets. To this end, we developed a new sampler inspired by diversity metrics in ecology, named Greedy Maximum Entropy sampler, or GME-sampler (https://github.com/idiap/gme-sampler). The strategic optimization of both balance and diversity of the selected items in the evaluation set is important given the resource-intensive nature of manual curation. After quantifying the noise in the training set, in the form of discrepancies between the input abstracts text and the expected output labels, we explored different strategies accordingly. Framing the task as an end-to-end Relation Extraction, we evaluated the performance of standard fine-tuning as a generative task and few-shot learning with open Large Language Models (LLaMA 7B-65B). In addition to their evaluation in few-shot settings, we explore the potential of open Large Language Models (Vicuna-13B) as synthetic data generator and propose a new workflow for this purpose. All evaluated models exhibited substantial improvements when fine-tuned on synthetic abstracts rather than the original noisy data. We provide our best performing (f1-score=59.0) BioGPT-Large model for end-to-end RE of natural-products relationships along with all the generated synthetic data and the evaluation dataset. See more details at https://github.com/idiap/abroad-re.

Genetic pathways usually encode molecular mechanisms that can inform targeted interventions. It is often challenging for existing machine learning approaches to jointly model genetic pathways (higher-order features) and variants (atomic features), and present to clinicians interpretable models. In order to build more accurate and better interpretable machine learning models for genetic medicine, we introduce Pathway Augmented Nonnegative Tensor factorization for HighER-order feature learning (PANTHER). PANTHER selects informative genetic pathways that directly encode molecular mechanisms. We apply genetically motivated constrained tensor factorization to group pathways in a way that reflects molecular mechanism interactions. We then train a softmax classifier for disease types using the identified pathway groups. We evaluated PANTHER against multiple state-of-the-art constrained tensor/matrix factorization models, as well as group guided and Bayesian hierarchical models. PANTHER outperforms all state-of-the-art comparison models significantly (p<0.05). Our experiments on large scale Next Generation Sequencing (NGS) and whole-genome genotyping datasets also demonstrated wide applicability of PANTHER. We performed feature analysis in predicting disease types, which suggested insights and benefits of the identified pathway groups.

Keyphrase generation is the task consisting in generating a set of words or phrases that highlight the main topics of a document. There are few datasets for keyphrase generation in the biomedical domain and they do not meet the expectations in terms of size for training generative models. In this paper, we introduce kp-biomed, the first large-scale biomedical keyphrase generation dataset with more than 5M documents collected from PubMed abstracts. We train and release several generative models and conduct a series of experiments showing that using large scale datasets improves significantly the performances for present and absent keyphrase generation. The dataset is available under CC-BY-NC v4.0 license at https://huggingface.co/ datasets/taln-ls2n/kpbiomed.

Major scandals in corporate history have urged the need for regulatory compliance, where organizations need to ensure that their controls (processes) comply with relevant laws, regulations, and policies. However, keeping track of the constantly changing legislation is difficult, thus organizations are increasingly adopting Regulatory Technology (RegTech) to facilitate the process. To this end, we introduce regulatory information retrieval (REG-IR), an application of document-to-document information retrieval (DOC2DOC IR), where the query is an entire document making the task more challenging than traditional IR where the queries are short. Furthermore, we compile and release two datasets based on the relationships between EU directives and UK legislation. We experiment on these datasets using a typical two-step pipeline approach comprising a pre-fetcher and a neural re-ranker. Experimenting with various pre-fetchers from BM25 to k nearest neighbors over representations from several BERT models, we show that fine-tuning a BERT model on an in-domain classification task produces the best representations for IR. We also show that neural re-rankers under-perform due to contradicting supervision, i.e., similar query-document pairs with opposite labels. Thus, they are biased towards the pre-fetcher's score. Interestingly, applying a date filter further improves the performance, showcasing the importance of the time dimension.

Inferring causal structure poses a combinatorial search problem that typically involves evaluating structures with a score or independence test. The resulting search is costly, and designing suitable scores or tests that capture prior knowledge is difficult. In this work, we propose to amortize causal structure learning. Rather than searching over structures, we train a variational inference model to directly predict the causal structure from observational or interventional data. This allows our inference model to acquire domain-specific inductive biases for causal discovery solely from data generated by a simulator, bypassing both the hand-engineering of suitable score functions and the search over graphs. The architecture of our inference model emulates permutation invariances that are crucial for statistical efficiency in structure learning, which facilitates generalization to significantly larger problem instances than seen during training. On synthetic data and semisynthetic gene expression data, our models exhibit robust generalization capabilities when subject to substantial distribution shifts and significantly outperform existing algorithms, especially in the challenging genomics domain. Our code and models are publicly available at: https://github.com/larslorch/avici.

We are now witnessing significant progress of deep learning methods in a variety of tasks (or datasets) of proteins. However, there is a lack of a standard benchmark to evaluate the performance of different methods, which hinders the progress of deep learning in this field. In this paper, we propose such a benchmark called PEER, a comprehensive and multi-task benchmark for Protein sEquence undERstanding. PEER provides a set of diverse protein understanding tasks including protein function prediction, protein localization prediction, protein structure prediction, protein-protein interaction prediction, and protein-ligand interaction prediction. We evaluate different types of sequence-based methods for each task including traditional feature engineering approaches, different sequence encoding methods as well as large-scale pre-trained protein language models. In addition, we also investigate the performance of these methods under the multi-task learning setting. Experimental results show that large-scale pre-trained protein language models achieve the best performance for most individual tasks, and jointly training multiple tasks further boosts the performance. The datasets and source codes of this benchmark are all available at https://github.com/DeepGraphLearning/PEER_Benchmark

A well-known limitation in pretrain-finetune paradigm lies in its inflexibility caused by the one-size-fits-all vocabulary. This potentially weakens the effect when applying pretrained models into natural language generation (NLG) tasks, especially for the subword distributions between upstream and downstream tasks with significant discrepancy. Towards approaching this problem, we extend the vanilla pretrain-finetune pipeline with an extra embedding transfer step. Specifically, a plug-and-play embedding generator is introduced to produce the representation of any input token, according to pre-trained embeddings of its morphologically similar ones. Thus, embeddings of mismatch tokens in downstream tasks can also be efficiently initialized. We conduct experiments on a variety of NLG tasks under the pretrain-finetune fashion. Experimental results and extensive analyses show that the proposed strategy offers us opportunities to feel free to transfer the vocabulary, leading to more efficient and better performed downstream NLG models.

Automatic phenotype concept recognition from unstructured text remains a challenging task in biomedical text mining research. Previous works that address the task typically use dictionary-based matching methods, which can achieve high precision but suffer from lower recall. Recently, machine learning-based methods have been proposed to identify biomedical concepts, which can recognize more unseen concept synonyms by automatic feature learning. However, most methods require large corpora of manually annotated data for model training, which is difficult to obtain due to the high cost of human annotation. In this paper, we propose PhenoTagger, a hybrid method that combines both dictionary and machine learning-based methods to recognize Human Phenotype Ontology (HPO) concepts in unstructured biomedical text. We first use all concepts and synonyms in HPO to construct a dictionary, which is then used to automatically build a distantly supervised training dataset for machine learning. Next, a cutting-edge deep learning model is trained to classify each candidate phrase (n-gram from input sentence) into a corresponding concept label. Finally, the dictionary and machine learning-based prediction results are combined for improved performance. Our method is validated with two HPO corpora, and the results show that PhenoTagger compares favorably to previous methods. In addition, to demonstrate the generalizability of our method, we retrained PhenoTagger using the disease ontology MEDIC for disease concept recognition to investigate the effect of training on different ontologies. Experimental results on the NCBI disease corpus show that PhenoTagger without requiring manually annotated training data achieves competitive performance as compared with state-of-the-art supervised methods.

Sequence-to-sequence (seq2seq) learning is a popular fashion for large-scale pretraining language models. However, the prior seq2seq pretraining models generally focus on reconstructive objectives on the decoder side and neglect the effect of encoder-side supervision, which we argue may lead to sub-optimal performance. To verify our hypothesis, we first empirically study the functionalities of the encoder and decoder in seq2seq pretrained language models, and find that the encoder takes an important but under-exploitation role than the decoder regarding the downstream performance and neuron activation. Therefore, we propose an encoding-enhanced seq2seq pretraining strategy, namely E2S2, which improves the seq2seq models via integrating more efficient self-supervised information into the encoders. Specifically, E2S2 adopts two self-supervised objectives on the encoder side from two aspects: 1) locally denoising the corrupted sentence (denoising objective); and 2) globally learning better sentence representations (contrastive objective). With the help of both objectives, the encoder can effectively distinguish the noise tokens and capture high-level (i.e. syntactic and semantic) knowledge, thus strengthening the ability of seq2seq model to accurately achieve the conditional generation. On a large diversity of downstream natural language understanding and generation tasks, E2S2 dominantly improves the performance of its powerful backbone models, e.g. BART and T5. For example, upon BART backbone, we achieve +1.1% averaged gain on the general language understanding evaluation (GLUE) benchmark and +1.75% F_0.5 score improvement on CoNLL2014 dataset. We also provide in-depth analyses to show the improvement stems from better linguistic representation. We hope that our work will foster future self-supervision research on seq2seq language model pretraining.

Clinical data in hospitals are increasingly accessible for research through clinical data warehouses, however these documents are unstructured. It is therefore necessary to extract information from medical reports to conduct clinical studies. Transfer learning with BERT-like models such as CamemBERT has allowed major advances, especially for named entity recognition. However, these models are trained for plain language and are less efficient on biomedical data. This is why we propose a new French public biomedical dataset on which we have continued the pre-training of CamemBERT. Thus, we introduce a first version of CamemBERT-bio, a specialized public model for the French biomedical domain that shows 2.54 points of F1 score improvement on average on different biomedical named entity recognition tasks. Our findings demonstrate the success of continual pre-training from a French model and contrast with recent proposals on the same domain and language. One of our key contributions highlights the importance of using a standard evaluation protocol that enables a clear view of the current state-of-the-art for French biomedical models.

Name tagging is a key component of Information Extraction (IE), particularly in scientific domains such as biomedicine and chemistry, where large language models (LLMs), e.g., ChatGPT, fall short. We investigate the applicability of transfer learning for enhancing a name tagging model trained in the biomedical domain (the source domain) to be used in the chemical domain (the target domain). A common practice for training such a model in a few-shot learning setting is to pretrain the model on the labeled source data, and then, to finetune it on a hand-full of labeled target examples. In our experiments we observed that such a model is prone to mis-labeling the source entities, which can often appear in the text, as the target entities. To alleviate this problem, we propose a model to transfer the knowledge from the source domain to the target domain, however, at the same time, to project the source entities and target entities into separate regions of the feature space. This diminishes the risk of mis-labeling the source entities as the target entities. Our model consists of two stages: 1) entity grouping in the source domain, which incorporates knowledge from annotated events to establish relations between entities, and 2) entity discrimination in the target domain, which relies on pseudo labeling and contrastive learning to enhance discrimination between the entities in the two domains. We carry out our extensive experiments across three source and three target datasets, and demonstrate that our method outperforms the baselines, in some scenarios by 5\% absolute value.

Despite the remarkable ability of large language models (LMs) to comprehend and generate language, they have a tendency to hallucinate and create factually inaccurate output. Augmenting LMs by retrieving information from external knowledge resources is one promising solution. Most existing retrieval augmented LMs employ a retrieve-and-generate setup that only retrieves information once based on the input. This is limiting, however, in more general scenarios involving generation of long texts, where continually gathering information throughout generation is essential. In this work, we provide a generalized view of active retrieval augmented generation, methods that actively decide when and what to retrieve across the course of the generation. We propose Forward-Looking Active REtrieval augmented generation (FLARE), a generic method which iteratively uses a prediction of the upcoming sentence to anticipate future content, which is then utilized as a query to retrieve relevant documents to regenerate the sentence if it contains low-confidence tokens. We test FLARE along with baselines comprehensively over 4 long-form knowledge-intensive generation tasks/datasets. FLARE achieves superior or competitive performance on all tasks, demonstrating the effectiveness of our method. Code and datasets are available at https://github.com/jzbjyb/FLARE.

Since BERT appeared, Transformer language models and transfer learning have become state-of-the-art for Natural Language Understanding tasks. Recently, some works geared towards pre-training specially-crafted models for particular domains, such as scientific papers, medical documents, user-generated texts, among others. These domain-specific models have been shown to improve performance significantly in most tasks. However, for languages other than English such models are not widely available. In this work, we present RoBERTuito, a pre-trained language model for user-generated text in Spanish, trained on over 500 million tweets. Experiments on a benchmark of tasks involving user-generated text showed that RoBERTuito outperformed other pre-trained language models in Spanish. In addition to this, our model achieves top results for some English-Spanish tasks of the Linguistic Code-Switching Evaluation benchmark (LinCE) and has also competitive performance against monolingual models in English tasks. To facilitate further research, we make RoBERTuito publicly available at the HuggingFace model hub together with the dataset used to pre-train it.

The approval success rate of drug candidates is very low with the majority of failure due to safety and efficacy. Increasingly available high dimensional information on targets, drug molecules and indications provides an opportunity for ML methods to integrate multiple data modalities and better predict clinically promising drug targets. Notably, drug targets with human genetics evidence are shown to have better odds to succeed. However, a recent tensor factorization-based approach found that additional information on targets and indications might not necessarily improve the predictive accuracy. Here we revisit this approach by integrating different types of human genetics evidence collated from publicly available sources to support each target-indication pair. We use Bayesian tensor factorization to show that models incorporating all available human genetics evidence (rare disease, gene burden, common disease) modestly improves the clinical outcome prediction over models using single line of genetics evidence. We provide additional insight into the relative predictive power of different types of human genetics evidence for predicting the success of clinical outcomes.

The impressive capabilities of recent language models can be largely attributed to the multi-trillion token pretraining datasets that they are trained on. However, model developers fail to disclose their construction methodology which has lead to a lack of open information on how to develop effective pretraining sets. To address this issue, we perform the first systematic study across the entire pipeline of pretraining set construction. First, we run ablations on existing techniques for pretraining set development to identify which methods translate to the largest gains in model accuracy on downstream evaluations. Then, we categorize the most widely used data source, web crawl snapshots, across the attributes of toxicity, quality, type of speech, and domain. Finally, we show how such attribute information can be used to further refine and improve the quality of a pretraining set. These findings constitute an actionable set of steps that practitioners can use to develop high quality pretraining sets.

In domains ranging from computer vision to natural language processing, machine learning models have been shown to exhibit stark disparities, often performing worse for members of traditionally underserved groups. One factor contributing to these performance gaps is a lack of representation in the data the models are trained on. It is often unclear, however, how to operationalize representativeness in specific applications. Here we formalize the problem of creating equitable training datasets, and propose a statistical framework for addressing this problem. We consider a setting where a model builder must decide how to allocate a fixed data collection budget to gather training data from different subgroups. We then frame dataset creation as a constrained optimization problem, in which one maximizes a function of group-specific performance metrics based on (estimated) group-specific learning rates and costs per sample. This flexible approach incorporates preferences of model-builders and other stakeholders, as well as the statistical properties of the learning task. When data collection decisions are made sequentially, we show that under certain conditions this optimization problem can be efficiently solved even without prior knowledge of the learning rates. To illustrate our approach, we conduct a simulation study of polygenic risk scores on synthetic genomic data -- an application domain that often suffers from non-representative data collection. We find that our adaptive sampling strategy outperforms several common data collection heuristics, including equal and proportional sampling, demonstrating the value of strategic dataset design for building equitable models.

As the capabilities of language models continue to advance, it is conceivable that "one-size-fits-all" model will remain as the main paradigm. For instance, given the vast number of languages worldwide, many of which are low-resource, the prevalent practice is to pretrain a single model on multiple languages. In this paper, we add to the growing body of evidence that challenges this practice, demonstrating that monolingual pretraining on the target language significantly improves models already extensively trained on diverse corpora. More specifically, we further pretrain GPT-J and LLaMA models on Portuguese texts using 3% or less of their original pretraining budget. Few-shot evaluations on Poeta, a suite of 14 Portuguese datasets, reveal that our models outperform English-centric and multilingual counterparts by a significant margin. Our best model, Sabi\'a-65B, performs on par with GPT-3.5-turbo. By evaluating on datasets originally conceived in the target language as well as translated ones, we study the contributions of language-specific pretraining in terms of 1) capturing linguistic nuances and structures inherent to the target language, and 2) enriching the model's knowledge about a domain or culture. Our results indicate that the majority of the benefits stem from the domain-specific knowledge acquired through monolingual pretraining.

Annotating training data for sequence tagging of texts is usually very time-consuming. Recent advances in transfer learning for natural language processing in conjunction with active learning open the possibility to significantly reduce the necessary annotation budget. We are the first to thoroughly investigate this powerful combination for the sequence tagging task. We conduct an extensive empirical study of various Bayesian uncertainty estimation methods and Monte Carlo dropout options for deep pre-trained models in the active learning framework and find the best combinations for different types of models. Besides, we also demonstrate that to acquire instances during active learning, a full-size Transformer can be substituted with a distilled version, which yields better computational performance and reduces obstacles for applying deep active learning in practice.

New astronomical tasks are often related to earlier tasks for which labels have already been collected. We adapt the contrastive framework BYOL to leverage those labels as a pretraining task while also enforcing augmentation invariance. For large-scale pretraining, we introduce GZ-Evo v0.1, a set of 96.5M volunteer responses for 552k galaxy images plus a further 1.34M comparable unlabelled galaxies. Most of the 206 GZ-Evo answers are unknown for any given galaxy, and so our pretraining task uses a Dirichlet loss that naturally handles unknown answers. GZ-Evo pretraining, with or without hybrid learning, improves on direct training even with plentiful downstream labels (+4% accuracy with 44k labels). Our hybrid pretraining/contrastive method further improves downstream accuracy vs. pretraining or contrastive learning, especially in the low-label transfer regime (+6% accuracy with 750 labels).

Diffusion models excel at capturing the natural design spaces of images, molecules, DNA, RNA, and protein sequences. However, rather than merely generating designs that are natural, we often aim to optimize downstream reward functions while preserving the naturalness of these design spaces. Existing methods for achieving this goal often require ``differentiable'' proxy models (e.g., classifier guidance or DPS) or involve computationally expensive fine-tuning of diffusion models (e.g., classifier-free guidance, RL-based fine-tuning). In our work, we propose a new method to address these challenges. Our algorithm is an iterative sampling method that integrates soft value functions, which looks ahead to how intermediate noisy states lead to high rewards in the future, into the standard inference procedure of pre-trained diffusion models. Notably, our approach avoids fine-tuning generative models and eliminates the need to construct differentiable models. This enables us to (1) directly utilize non-differentiable features/reward feedback, commonly used in many scientific domains, and (2) apply our method to recent discrete diffusion models in a principled way. Finally, we demonstrate the effectiveness of our algorithm across several domains, including image generation, molecule generation, and DNA/RNA sequence generation. The code is available at https://github.com/masa-ue/SVDD{https://github.com/masa-ue/SVDD}.

Gene expression can be used to subtype breast cancer with improved prediction of risk of recurrence and treatment responsiveness over that obtained using routine immunohistochemistry (IHC). However, in the clinic, molecular profiling is primarily used for ER+ breast cancer, which is costly, tissue destructive, requires specialized platforms and takes several weeks to obtain a result. Deep learning algorithms can effectively extract morphological patterns in digital histopathology images to predict molecular phenotypes quickly and cost-effectively. We propose a new, computationally efficient approach called hist2RNA inspired by bulk RNA-sequencing techniques to predict the expression of 138 genes (incorporated from six commercially available molecular profiling tests), including luminal PAM50 subtype, from hematoxylin and eosin (H&E) stained whole slide images (WSIs). The training phase involves the aggregation of extracted features for each patient from a pretrained model to predict gene expression at the patient level using annotated H&E images from The Cancer Genome Atlas (TCGA, n=335). We demonstrate successful gene prediction on a held-out test set (n = 160, corr = 0.82 across patients, corr = 0.29 across genes) and perform exploratory analysis on an external tissue microarray (TMA) dataset (n = 498) with known IHC and survival information. Our model is able to predict gene expression and luminal PAM50 subtype (Luminal A versus Luminal B) on the TMA dataset with prognostic significance for overall survival in univariate analysis (c-index = 0.56, hazard ratio = 2.16 (95% CI 1.12-3.06), p < 5 x 10-3), and independent significance in multivariate analysis incorporating standard clinicopathological variables (c-index = 0.65, hazard ratio = 1.85 (95% CI 1.30-2.68), p < 5 x 10-3).

stream-learn is a Python package compatible with scikit-learn and developed for the drifting and imbalanced data stream analysis. Its main component is a stream generator, which allows to produce a synthetic data stream that may incorporate each of the three main concept drift types (i.e. sudden, gradual and incremental drift) in their recurring or non-recurring versions. The package allows conducting experiments following established evaluation methodologies (i.e. Test-Then-Train and Prequential). In addition, estimators adapted for data stream classification have been implemented, including both simple classifiers and state-of-art chunk-based and online classifier ensembles. To improve computational efficiency, package utilises its own implementations of prediction metrics for imbalanced binary classification tasks.

Pre-trained language models (PLMs), such as BERT and GPT, have revolutionized the field of NLP, not only in the general domain but also in the biomedical domain. Most prior efforts in building biomedical PLMs have resorted simply to domain adaptation and focused mainly on English. In this work we introduce eHealth, a Chinese biomedical PLM built from scratch with a new pre-training framework. This new framework pre-trains eHealth as a discriminator through both token- and sequence-level discrimination. The former is to detect input tokens corrupted by a generator and recover their original identities from plausible candidates, while the latter is to further distinguish corruptions of a same original sequence from those of others. As such, eHealth can learn language semantics at both token and sequence levels. Extensive experiments on 11 Chinese biomedical language understanding tasks of various forms verify the effectiveness and superiority of our approach. We release the pre-trained model at https://github.com/PaddlePaddle/Research/tree/master/KG/eHealth and will also release the code later.

State-of-the-art neural rankers pre-trained on large task-specific training data such as MS-MARCO, have been shown to exhibit strong performance on various ranking tasks without domain adaptation, also called zero-shot. However, zero-shot neural ranking may be sub-optimal, as it does not take advantage of the target domain information. Unfortunately, acquiring sufficiently large and high quality target training data to improve a modern neural ranker can be costly and time-consuming. To address this problem, we propose a new approach to unsupervised domain adaptation for ranking, DUQGen, which addresses a critical gap in prior literature, namely how to automatically generate both effective and diverse synthetic training data to fine tune a modern neural ranker for a new domain. Specifically, DUQGen produces a more effective representation of the target domain by identifying clusters of similar documents; and generates a more diverse training dataset by probabilistic sampling over the resulting document clusters. Our extensive experiments, over the standard BEIR collection, demonstrate that DUQGen consistently outperforms all zero-shot baselines and substantially outperforms the SOTA baselines on 16 out of 18 datasets, for an average of 4% relative improvement across all datasets. We complement our results with a thorough analysis for more in-depth understanding of the proposed method's performance and to identify promising areas for further improvements.

Large language models (LLMs) have notably enhanced the fluency and diversity of machine-generated text. However, this progress also presents a significant challenge in detecting the origin of a given text, and current research on detection methods lags behind the rapid evolution of LLMs. Conventional training-based methods have limitations in flexibility, particularly when adapting to new domains, and they often lack explanatory power. To address this gap, we propose a novel training-free detection strategy called Divergent N-Gram Analysis (DNA-GPT). Given a text, we first truncate it in the middle and then use only the preceding portion as input to the LLMs to regenerate the new remaining parts. By analyzing the differences between the original and new remaining parts through N-gram analysis in black-box or probability divergence in white-box, we can clearly illustrate significant discrepancies between machine-generated and human-written text. We conducted extensive experiments on the most advanced LLMs from OpenAI, including text-davinci-003, GPT-3.5-turbo, and GPT-4, as well as open-source models such as GPT-NeoX-20B and LLaMa-13B. Results show that our zero-shot approach exhibits state-of-the-art performance in distinguishing between human and GPT-generated text on four English and one German dataset, outperforming OpenAI's own classifier, which is trained on millions of text. Additionally, our methods provide reasonable explanations and evidence to support our claim, which is a unique feature of explainable detection. Our method is also robust under the revised text attack and can additionally solve model sourcing. Codes are available at https://github.com/Xianjun-Yang/DNA-GPT.

This report introduces xGen-MM (also known as BLIP-3), a framework for developing Large Multimodal Models (LMMs). The framework comprises meticulously curated datasets, a training recipe, model architectures, and a resulting suite of LMMs. xGen-MM, short for xGen-MultiModal, expands the Salesforce xGen initiative on foundation AI models. Our models undergo rigorous evaluation across a range of tasks, including both single and multi-image benchmarks. Our pre-trained base model exhibits strong in-context learning capabilities and the instruction-tuned model demonstrates competitive performance among open-source LMMs with similar model sizes. In addition, we introduce a safety-tuned model with DPO, aiming to mitigate harmful behaviors such as hallucinations and improve safety. We open-source our models, curated large-scale datasets, and our fine-tuning codebase to facilitate further advancements in LMM research. Associated resources will be available on our project page above.

Machine learning, notably deep learning, has significantly propelled molecular investigations within the biochemical sphere. Traditionally, modeling for such research has centered around a handful of paradigms. For instance, the prediction paradigm is frequently deployed for tasks such as molecular property prediction. To enhance the generation and decipherability of purely data-driven models, scholars have integrated biochemical domain knowledge into these molecular study models. This integration has sparked a surge in paradigm transfer, which is solving one molecular learning task by reformulating it as another one. With the emergence of Large Language Models, these paradigms have demonstrated an escalating trend towards harmonized unification. In this work, we delineate a literature survey focused on knowledge-informed molecular learning from the perspective of paradigm transfer. We classify the paradigms, scrutinize their methodologies, and dissect the contribution of domain knowledge. Moreover, we encapsulate prevailing trends and identify intriguing avenues for future exploration in molecular learning.

Generative pre-trained Transformer (GPT) has demonstrates its great success in natural language processing and related techniques have been adapted into molecular modeling. Considering that text is the most important record for scientific discovery, in this paper, we propose MolXPT, a unified language model of text and molecules pre-trained on SMILES (a sequence representation of molecules) wrapped by text. Briefly, we detect the molecule names in each sequence and replace them to the corresponding SMILES. In this way, the SMILES could leverage the information from surrounding text, and vice versa. The above wrapped sequences, text sequences from PubMed and SMILES sequences from PubChem are all fed into a language model for pre-training. Experimental results demonstrate that MolXPT outperforms strong baselines of molecular property prediction on MoleculeNet, performs comparably to the best model in text-molecule translation while using less than half of its parameters, and enables zero-shot molecular generation without finetuning.

Heterogenity of data-to-text generation datasets limits the research on data-to-text generation systems. We present TabGenie - a toolkit which enables researchers to explore, preprocess, and analyze a variety of data-to-text generation datasets through the unified framework of table-to-text generation. In TabGenie, all the inputs are represented as tables with associated metadata. The tables can be explored through the web interface, which also provides an interactive mode for debugging table-to-text generation, facilitates side-by-side comparison of generated system outputs, and allows easy exports for manual analysis. Furthermore, TabGenie is equipped with command line processing tools and Python bindings for unified dataset loading and processing. We release TabGenie as a PyPI package and provide its open-source code and a live demo at https://github.com/kasnerz/tabgenie.

With the development of large language models (LLMs), zero-shot learning has attracted much attention for various NLP tasks. Different from prior works that generate training data with billion-scale natural language generation (NLG) models, we propose a retrieval-enhanced framework to create training data from a general-domain unlabeled corpus. To realize this, we first conduct contrastive pretraining to learn an unsupervised dense retriever for extracting the most relevant documents using class-descriptive verbalizers. We then further propose two simple strategies, namely Verbalizer Augmentation with Demonstrations and Self-consistency Guided Filtering to improve the topic coverage of the dataset while removing noisy examples. Experiments on nine datasets demonstrate that REGEN achieves 4.3% gain over the strongest baselines and saves around 70% of the time compared to baselines using large NLG models. Besides, REGEN can be naturally integrated with recently proposed large language models to boost performance.

Recent advancements in specialized large-scale architectures for training image and language have profoundly impacted the field of computer vision and natural language processing (NLP). Language models, such as the recent ChatGPT and GPT4 have demonstrated exceptional capabilities in processing, translating, and generating human languages. These breakthroughs have also been reflected in protein research, leading to the rapid development of numerous new methods in a short time, with unprecedented performance. Language models, in particular, have seen widespread use in protein research, as they have been utilized to embed proteins, generate novel ones, and predict tertiary structures. In this book chapter, we provide an overview of the use of protein generative models, reviewing 1) language models for the design of novel artificial proteins, 2) works that use non-Transformer architectures, and 3) applications in directed evolution approaches.

Language models pretrained on text from a wide variety of sources form the foundation of today's NLP. In light of the success of these broad-coverage models, we investigate whether it is still helpful to tailor a pretrained model to the domain of a target task. We present a study across four domains (biomedical and computer science publications, news, and reviews) and eight classification tasks, showing that a second phase of pretraining in-domain (domain-adaptive pretraining) leads to performance gains, under both high- and low-resource settings. Moreover, adapting to the task's unlabeled data (task-adaptive pretraining) improves performance even after domain-adaptive pretraining. Finally, we show that adapting to a task corpus augmented using simple data selection strategies is an effective alternative, especially when resources for domain-adaptive pretraining might be unavailable. Overall, we consistently find that multi-phase adaptive pretraining offers large gains in task performance.

Generic pre-trained neural networks may struggle to produce good results in specialized domains like finance and insurance. This is due to a domain mismatch between training data and downstream tasks, as in-domain data are often scarce due to privacy constraints. In this work, we compare different pre-training strategies for LayoutLM. We show that using domain-relevant documents improves results on a named-entity recognition (NER) problem using a novel dataset of anonymized insurance-related financial documents called Payslips. Moreover, we show that we can achieve competitive results using a smaller and faster model.

Retrieval Augmented Generation (RAG) system is important in domains such as e-commerce, which has many long-tail entities and frequently updated information. Most existing works adopt separate modules for retrieval and generation, which may be suboptimal since the retrieval task and the generation task cannot benefit from each other to improve performance. We propose a novel Backbone Shared RAG framework (BSharedRAG). It first uses a domain-specific corpus to continually pre-train a base model as a domain-specific backbone model and then trains two plug-and-play Low-Rank Adaptation (LoRA) modules based on the shared backbone to minimize retrieval and generation losses respectively. Experimental results indicate that our proposed BSharedRAG outperforms baseline models by 5% and 13% in Hit@3 upon two datasets in retrieval evaluation and by 23% in terms of BLEU-3 in generation evaluation. Our codes, models, and dataset are available at https://bsharedrag.github.io.

The task of Grammatical Error Correction (GEC) has received remarkable attention with wide applications in Natural Language Processing (NLP) in recent years. While one of the key principles of GEC is to keep the correct parts unchanged and avoid over-correction, previous sequence-to-sequence (seq2seq) models generate results from scratch, which are not guaranteed to follow the original sentence structure and may suffer from the over-correction problem. In the meantime, the recently proposed sequence tagging models can overcome the over-correction problem by only generating edit operations, but are conditioned on human designed language-specific tagging labels. In this paper, we combine the pros and alleviate the cons of both models by proposing a novel Sequence-to-Action~(S2A) module. The S2A module jointly takes the source and target sentences as input, and is able to automatically generate a token-level action sequence before predicting each token, where each action is generated from three choices named SKIP, COPY and GENerate. Then the actions are fused with the basic seq2seq framework to provide final predictions. We conduct experiments on the benchmark datasets of both English and Chinese GEC tasks. Our model consistently outperforms the seq2seq baselines, while being able to significantly alleviate the over-correction problem as well as holding better generality and diversity in the generation results compared to the sequence tagging models.

Drug discovery typically consists of multiple steps, including identifying a target protein key to a disease's etiology, validating that interacting with this target could prevent symptoms or cure the disease, discovering a small molecule or biologic therapeutic to interact with it, and optimizing the candidate molecule through a complex landscape of required properties. Drug discovery related tasks often involve prediction and generation while considering multiple entities that potentially interact, which poses a challenge for typical AI models. For this purpose we present MAMMAL - Molecular Aligned Multi-Modal Architecture and Language - a method that we applied to create a versatile multi-task foundation model ibm/biomed.omics.bl.sm.ma-ted-458m that learns from large-scale biological datasets (2 billion samples) across diverse modalities, including proteins, small molecules, and genes. We introduce a prompt syntax that supports a wide range of classification, regression, and generation tasks. It allows combining different modalities and entity types as inputs and/or outputs. Our model handles combinations of tokens and scalars and enables the generation of small molecules and proteins, property prediction, and transcriptomic lab test predictions. We evaluated the model on 11 diverse downstream tasks spanning different steps within a typical drug discovery pipeline, where it reaches new SOTA in 9 tasks and is comparable to SOTA in 2 tasks. This performance is achieved while using a unified architecture serving all tasks, in contrast to the original SOTA performance achieved using tailored architectures. The model code and pretrained weights are publicly available at https://github.com/BiomedSciAI/biomed-multi-alignment and https://huggingface.co/ibm/biomed.omics.bl.sm.ma-ted-458m.

The transformer architecture has revolutionized bioinformatics and driven progress in the understanding and prediction of the properties of biomolecules. Almost all research on large-scale biosequence transformers has focused on one domain at a time (single-omic), usually nucleotides or peptides. These models have seen incredible success in downstream tasks in each domain and have achieved particularly noteworthy breakthroughs in sequences of peptides and structural modeling. However, these single-omic models are naturally incapable of modeling multi-omic tasks, one of the most biologically critical being nucleotide-peptide interactions. We present our work training the first multi-omic nucleotide-peptide foundation models. We show that these multi-omic models (MOMs) can learn joint representations between various single-omic distributions that are emergently consistent with the Central Dogma of molecular biology, despite only being trained on unlabeled biosequences. We further demonstrate that MOMs can be fine-tuned to achieve state-of-the-art results on peptide-nucleotide interaction tasks, namely predicting the change in Gibbs free energy ({\Delta}G) of the binding interaction between a given oligonucleotide and peptide, as well as the effect on this binding interaction due to mutations in the oligonucleotide sequence ({\Delta}{\Delta}G). Remarkably, we show that multi-omic biosequence transformers emergently learn useful structural information without any prior structural training, allowing us to predict which peptide residues are most involved in the peptide-nucleotide binding interaction. Lastly, we provide evidence that multi-omic biosequence models are non-inferior to foundation models trained on single-omics distributions, suggesting a more generalized or foundational approach to building these models.

Pre-trained language models have been successful in many knowledge-intensive NLP tasks. However, recent work has shown that models such as BERT are not ``structurally ready'' to aggregate textual information into a [CLS] vector for dense passage retrieval (DPR). This ``lack of readiness'' results from the gap between language model pre-training and DPR fine-tuning. Previous solutions call for computationally expensive techniques such as hard negative mining, cross-encoder distillation, and further pre-training to learn a robust DPR model. In this work, we instead propose to fully exploit knowledge in a pre-trained language model for DPR by aggregating the contextualized token embeddings into a dense vector, which we call agg*. By concatenating vectors from the [CLS] token and agg*, our Aggretriever model substantially improves the effectiveness of dense retrieval models on both in-domain and zero-shot evaluations without introducing substantial training overhead. Code is available at https://github.com/castorini/dhr

We report a flexible language-model based deep learning strategy, applied here to solve complex forward and inverse problems in protein modeling, based on an attention neural network that integrates transformer and graph convolutional architectures in a causal multi-headed graph mechanism, to realize a generative pretrained model. The model is applied to predict secondary structure content (per-residue level and overall content), protein solubility, and sequencing tasks. Further trained on inverse tasks, the model is rendered capable of designing proteins with these properties as target features. The model is formulated as a general framework, completely prompt-based, and can be adapted for a variety of downstream tasks. We find that adding additional tasks yields emergent synergies that the model exploits in improving overall performance, beyond what would be possible by training a model on each dataset alone. Case studies are presented to validate the method, yielding protein designs specifically focused on structural proteins, but also exploring the applicability in the design of soluble, antimicrobial biomaterials. While our model is trained to ultimately perform 8 distinct tasks, with available datasets it can be extended to solve additional problems. In a broader sense, this work illustrates a form of multiscale modeling that relates a set of ultimate building blocks (here, byte-level utf8 characters) to complex output. This materiomic scheme captures complex emergent relationships between universal building block and resulting properties via a synergizing learning capacity to express a set of potentialities embedded in the knowledge used in training, via the interplay of universality and diversity.

Recent advancements in biological research leverage the integration of molecules, proteins, and natural language to enhance drug discovery. However, current models exhibit several limitations, such as the generation of invalid molecular SMILES, underutilization of contextual information, and equal treatment of structured and unstructured knowledge. To address these issues, we propose BioT5, a comprehensive pre-training framework that enriches cross-modal integration in biology with chemical knowledge and natural language associations. BioT5 utilizes SELFIES for 100% robust molecular representations and extracts knowledge from the surrounding context of bio-entities in unstructured biological literature. Furthermore, BioT5 distinguishes between structured and unstructured knowledge, leading to more effective utilization of information. After fine-tuning, BioT5 shows superior performance across a wide range of tasks, demonstrating its strong capability of capturing underlying relations and properties of bio-entities. Our code is available at https://github.com/QizhiPei/BioT5{Github}.

We explore the abilities of character recurrent neural network (char-RNN) for hashtag segmentation. Our approach to the task is the following: we generate synthetic training dataset according to frequent n-grams that satisfy predefined morpho-syntactic patterns to avoid any manual annotation. The active learning strategy limits the training dataset and selects informative training subset. The approach does not require any language-specific settings and is compared for two languages, which differ in inflection degree.

Language models can serve as a valuable tool for software developers to increase productivity. Large generative models can be used for code generation and code completion, while smaller encoder-only models are capable of performing code search tasks using natural language queries.These capabilities are heavily influenced by the quality and diversity of the available training data. Source code datasets used for training usually focus on the most popular languages and testing is mostly conducted on the same distributions, often overlooking low-resource programming languages. Motivated by the NLP generalization taxonomy proposed by Hupkes et.\,al., we propose a new benchmark dataset called GenCodeSearchNet (GeCS) which builds upon existing natural language code search datasets to systemically evaluate the programming language understanding generalization capabilities of language models. As part of the full dataset, we introduce a new, manually curated subset StatCodeSearch that focuses on R, a popular but so far underrepresented programming language that is often used by researchers outside the field of computer science. For evaluation and comparison, we collect several baseline results using fine-tuned BERT-style models and GPT-style large language models in a zero-shot setting.

Large Language Models (LLMs), including GPT-x and LLaMA2, have achieved remarkable performance in multiple Natural Language Processing (NLP) tasks. Under the premise that protein sequences constitute the protein language, Protein Large Language Models (ProLLMs) trained on protein corpora excel at de novo protein sequence generation. However, as of now, unlike LLMs in NLP, no ProLLM is capable of multiple tasks in the Protein Language Processing (PLP) field. This prompts us to delineate the inherent limitations in current ProLLMs: (i) the lack of natural language capabilities, (ii) insufficient instruction understanding, and (iii) high training resource demands. To address these challenges, we introduce a training framework to transform any general LLM into a ProLLM capable of handling multiple PLP tasks. Specifically, our framework utilizes low-rank adaptation and employs a two-stage training approach, and it is distinguished by its universality, low overhead, and scalability. Through training under this framework, we propose the ProLLaMA model, the first known ProLLM to handle multiple PLP tasks simultaneously. Experiments show that ProLLaMA achieves state-of-the-art results in the unconditional protein sequence generation task. In the controllable protein sequence generation task, ProLLaMA can design novel proteins with desired functionalities. In the protein property prediction task, ProLLaMA achieves nearly 100\% accuracy across many categories. The latter two tasks are beyond the reach of other ProLLMs. Code is available at https://github.com/Lyu6PosHao/ProLLaMA.

Many machine learning tasks can be expressed as the transformation---or transduction---of input sequences into output sequences: speech recognition, machine translation, protein secondary structure prediction and text-to-speech to name but a few. One of the key challenges in sequence transduction is learning to represent both the input and output sequences in a way that is invariant to sequential distortions such as shrinking, stretching and translating. Recurrent neural networks (RNNs) are a powerful sequence learning architecture that has proven capable of learning such representations. However RNNs traditionally require a pre-defined alignment between the input and output sequences to perform transduction. This is a severe limitation since finding the alignment is the most difficult aspect of many sequence transduction problems. Indeed, even determining the length of the output sequence is often challenging. This paper introduces an end-to-end, probabilistic sequence transduction system, based entirely on RNNs, that is in principle able to transform any input sequence into any finite, discrete output sequence. Experimental results for phoneme recognition are provided on the TIMIT speech corpus.

The information retrieval community has recently witnessed a revolution due to large pretrained transformer models. Another key ingredient for this revolution was the MS MARCO dataset, whose scale and diversity has enabled zero-shot transfer learning to various tasks. However, not all IR tasks and domains can benefit from one single dataset equally. Extensive research in various NLP tasks has shown that using domain-specific training data, as opposed to a general-purpose one, improves the performance of neural models. In this work, we harness the few-shot capabilities of large pretrained language models as synthetic data generators for IR tasks. We show that models finetuned solely on our unsupervised dataset outperform strong baselines such as BM25 as well as recently proposed self-supervised dense retrieval methods. Furthermore, retrievers finetuned on both supervised and our synthetic data achieve better zero-shot transfer than models finetuned only on supervised data. Code, models, and data are available at https://github.com/zetaalphavector/inpars .

As opposed to scaling-up protein language models (PLMs), we seek improving performance via protein-specific optimization. Although the proportionality between the language model size and the richness of its learned representations is validated, we prioritize accessibility and pursue a path of data-efficient, cost-reduced, and knowledge-guided optimization. Through over twenty experiments ranging from masking, architecture, and pre-training data, we derive insights from protein-specific experimentation into building a model that interprets the language of life, optimally. We present Ankh, the first general-purpose PLM trained on Google's TPU-v4 surpassing the state-of-the-art performance with fewer parameters (<10% for pre-training, <7% for inference, and <30% for the embedding dimension). We provide a representative range of structure and function benchmarks where Ankh excels. We further provide a protein variant generation analysis on High-N and One-N input data scales where Ankh succeeds in learning protein evolutionary conservation-mutation trends and introducing functional diversity while retaining key structural-functional characteristics. We dedicate our work to promoting accessibility to research innovation via attainable resources.

Contrastive pretraining on parallel image-text data has attained great success in vision-language processing (VLP), as exemplified by CLIP and related methods. However, prior explorations tend to focus on general domains in the web. Biomedical images and text are rather different, but publicly available datasets are small and skew toward chest X-ray, thus severely limiting progress. In this paper, we conducted by far the largest study on biomedical VLP, using 15 million figure-caption pairs extracted from biomedical research articles in PubMed Central. Our dataset (PMC-15M) is two orders of magnitude larger than existing biomedical image-text datasets such as MIMIC-CXR, and spans a diverse range of biomedical images. The standard CLIP method is suboptimal for the biomedical domain. We propose BiomedCLIP with domain-specific adaptations tailored to biomedical VLP. We conducted extensive experiments and ablation studies on standard biomedical imaging tasks from retrieval to classification to visual question-answering (VQA). BiomedCLIP established new state of the art in a wide range of standard datasets, substantially outperformed prior VLP approaches. Surprisingly, BiomedCLIP even outperformed radiology-specific state-of-the-art models such as BioViL on radiology-specific tasks such as RSNA pneumonia detection, thus highlighting the utility in large-scale pretraining across all biomedical image types. We will release our models at https://aka.ms/biomedclip to facilitate future research in biomedical VLP.