Daily Papers

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

We present Compound Conditioned ControlNet, C3Net, a novel generative neural architecture taking conditions from multiple modalities and synthesizing multimodal contents simultaneously (e.g., image, text, audio). C3Net adapts the ControlNet architecture to jointly train and make inferences on a production-ready diffusion model and its trainable copies. Specifically, C3Net first aligns the conditions from multi-modalities to the same semantic latent space using modality-specific encoders based on contrastive training. Then, it generates multimodal outputs based on the aligned latent space, whose semantic information is combined using a ControlNet-like architecture called Control C3-UNet. Correspondingly, with this system design, our model offers an improved solution for joint-modality generation through learning and explaining multimodal conditions instead of simply taking linear interpolations on the latent space. Meanwhile, as we align conditions to a unified latent space, C3Net only requires one trainable Control C3-UNet to work on multimodal semantic information. Furthermore, our model employs unimodal pretraining on the condition alignment stage, outperforming the non-pretrained alignment even on relatively scarce training data and thus demonstrating high-quality compound condition generation. We contribute the first high-quality tri-modal validation set to validate quantitatively that C3Net outperforms or is on par with first and contemporary state-of-the-art multimodal generation. Our codes and tri-modal dataset will be released.

This project aims to investigate a novel sequence generation method inspired by the AlphaGo paradigm, adapting it for use with large language models (LLMs). The proposed approach involves creating search trees of different possible completions and evaluating these completions based on model confidence. By considering various paths in the search tree and scoring them according to the model's confidence in each completion, we can generate diverse and high-quality sequences. This research explores the implementation of this paradigm by using confidence as a proxy for response quality akin to beam search vijayakumar2016diverse. The primary goal of this paper is to outline the paradigm and demonstrate its potential, rather than focusing on achieving perfect results. The paper will outline the reasons why we believe this paradigm has the potential to improve LLMs in the following manners: 1) increase output quality, 2) decrease errors, 3) eliminate or reduce the compound error problems, 4) generate diverse and creative completions, 5) allow for iterative problem-solving, and 6) self-training. We expect this approach to yield a set of diverse and coherent sequences, offering insights into balancing exploration and exploitation in sequence generation. Potential applications include creative text generation tasks, such as storytelling and content creation, as well as other natural language processing domains, like machine translation and automated summarization. The goal is that the model will be far more effective as it will be able to consider many possible variations allowing it to find the ideal completion. This research aims to contribute to the understanding of effective search strategies in sequence generation and their impact on generating high-quality, varied textual outputs.

The cascade of 2D geometric transformations were exploited to model relations between entities in a knowledge graph (KG), leading to an effective KG embedding (KGE) model, CompoundE. Furthermore, the rotation in the 3D space was proposed as a new KGE model, Rotate3D, by leveraging its non-commutative property. Inspired by CompoundE and Rotate3D, we leverage 3D compound geometric transformations, including translation, rotation, scaling, reflection, and shear and propose a family of KGE models, named CompoundE3D, in this work. CompoundE3D allows multiple design variants to match rich underlying characteristics of a KG. Since each variant has its own advantages on a subset of relations, an ensemble of multiple variants can yield superior performance. The effectiveness and flexibility of CompoundE3D are experimentally verified on four popular link prediction datasets.

For an artist or a graphic designer, the spatial layout of a scene is a critical design choice. However, existing text-to-image diffusion models provide limited support for incorporating spatial information. This paper introduces Composite Diffusion as a means for artists to generate high-quality images by composing from the sub-scenes. The artists can specify the arrangement of these sub-scenes through a flexible free-form segment layout. They can describe the content of each sub-scene primarily using natural text and additionally by utilizing reference images or control inputs such as line art, scribbles, human pose, canny edges, and more. We provide a comprehensive and modular method for Composite Diffusion that enables alternative ways of generating, composing, and harmonizing sub-scenes. Further, we wish to evaluate the composite image for effectiveness in both image quality and achieving the artist's intent. We argue that existing image quality metrics lack a holistic evaluation of image composites. To address this, we propose novel quality criteria especially relevant to composite generation. We believe that our approach provides an intuitive method of art creation. Through extensive user surveys, quantitative and qualitative analysis, we show how it achieves greater spatial, semantic, and creative control over image generation. In addition, our methods do not need to retrain or modify the architecture of the base diffusion models and can work in a plug-and-play manner with the fine-tuned models.

Quality estimation models have been developed to assess the corrections made by grammatical error correction (GEC) models when the reference or gold-standard corrections are not available. An ideal quality estimator can be utilized to combine the outputs of multiple GEC systems by choosing the best subset of edits from the union of all edits proposed by the GEC base systems. However, we found that existing GEC quality estimation models are not good enough in differentiating good corrections from bad ones, resulting in a low F0.5 score when used for system combination. In this paper, we propose GRECO, a new state-of-the-art quality estimation model that gives a better estimate of the quality of a corrected sentence, as indicated by having a higher correlation to the F0.5 score of a corrected sentence. It results in a combined GEC system with a higher F0.5 score. We also propose three methods for utilizing GEC quality estimation models for system combination with varying generality: model-agnostic, model-agnostic with voting bias, and model-dependent method. The combined GEC system outperforms the state of the art on the CoNLL-2014 test set and the BEA-2019 test set, achieving the highest F0.5 scores published to date.