app.py

# Uncomment if run locally
import os
#import sys
#
#sys.path.append(os.path.abspath("../../../molvault"))
#sys.path.insert(0, os.path.abspath(os.path.join(os.path.dirname(__file__), "..")))

from requests import head
from concrete.ml.deployment import FHEModelClient
import numpy
import os
from pathlib import Path
import requests
import json
import base64
import subprocess
import shutil
import time
from chemdata import get_ECFP_AND_FEATURES
import streamlit as st
import cairosvg
from rdkit import Chem
from rdkit.Chem import AllChem
from rdkit.Chem.Draw import rdMolDraw2D
import pandas as pd
from st_keyup import st_keyup
import pickle
import numpy as np
st.set_page_config(layout="wide", page_title="VaultChem")


def local_css(file_name):
    with open(file_name) as f:
        st.markdown(f"<style>{f.read()}</style>", unsafe_allow_html=True)


local_css("style.css")


def img_to_bytes(img_path):
    img_bytes = Path(img_path).read_bytes()
    encoded = base64.b64encode(img_bytes).decode()
    return encoded


def img_to_html(img_path, width=None):
    img_bytes = img_to_bytes(img_path)
    if width:
        img_html = "<img src='data:image/png;base64,{}' class='img-fluid' style='width:{};'>".format(
            img_bytes, width
        )
    else:
        img_html = "<img src='data:image/png;base64,{}' class='img-fluid'>".format(
            img_bytes
        )
    return img_html


# Start timing
formatted_text = (
    "<h1 style='text-align: center;'>"
    "<span style='color: red;'>Pharmacokinetics</span>"
    "<span style='color: black;'> of </span>"
    "<span style='color: blue;'>🤫confidential</span>"
    "<span style='color: black;'> molecules</span>"
    "</h1>"
)

st.markdown(formatted_text, unsafe_allow_html=True)

interesting_text = """
Machine learning (**ML**) has become a cornerstone of modern drug discovery. However, the data used to evaluate the ML models is often **confidential**.
This is especially true for the pharmaceutical industry where new drug candidates are considered as the most valuable asset.
Therefore chemical companies are reluctant to share their data with third parties, for instance, to use ML services provided by other companies.

🔒**We implemented a workflow that allows predicting properties of a molecule with third-party models without sharing them**🔒.
That means an organization "A" can use any server - even an untrusted environment - outside of their infrastructure to perform the prediction.
This way organization "A" can benefit from ML services provided by organization "B" without sharing their confidential data.

🪄 **The magic?** 🪄

The server on which the prediction is computed will never see the molecule in clear text, but will still compute an encrypted prediction.
Why is this **magic**? Because this is equivalent to computing the prediction on the molecule in clear text, but without sharing the molecule with the server.
Even if organization "B" - or in fact any other party - would try to steal the data, they would only see the encrypted molecular data.
**Only the party that has the private key (organization "A") can decrypt the prediction**. This is possible using a method called "Fully Homomorphic Encryption" (FHE). 
This special encryption scheme allows to perform computations on encrypted data, to learn more about FHE, click [here](https://fhe.org/resources/).

We use the open-source library <a href="https://github.com/zama-ai/concrete-ml" target="_blank">Concrete-ML</a> to develop safe and robust encryption technology.

The code used for the FHE prediction is available in the open-source library 
\n
**What are the steps involved?**
\n
Find out below! 👇 
You can try it for yourself! 🎉
"""

st.markdown(
    f"{interesting_text}",
    unsafe_allow_html=True,
)

st.divider()

st.markdown(
    "<p style='text-align: center; color: grey;'>"
    + img_to_html("scheme2.png", width="65%")
    + "</p>",
    unsafe_allow_html=True,
)

# Define your data
st.divider()


# This repository's directory
REPO_DIR = Path(__file__).parent
subprocess.Popen(["uvicorn", "server:app"], cwd=REPO_DIR)

# if not exists, create a directory for the FHE keys called .fhe_keys
if not os.path.exists(".fhe_keys"):
    os.mkdir(".fhe_keys")
# if not exists, create a directory for the tmp files called tmp
if not os.path.exists("tmp"):
    os.mkdir("tmp")


# Wait 4 sec for the server to start
time.sleep(4)

# Encrypted data limit for the browser to display
# (encrypted data is too large to display in the browser)
ENCRYPTED_DATA_BROWSER_LIMIT = 500
N_USER_KEY_STORED = 20


def clean_tmp_directory():
    # Allow 20 user keys to be stored.
    # Once that limitation is reached, deleted the oldest.
    path_sub_directories = sorted(
        [f for f in Path(".fhe_keys/").iterdir() if f.is_dir()], key=os.path.getmtime
    )

    user_ids = []
    if len(path_sub_directories) > N_USER_KEY_STORED:
        n_files_to_delete = len(path_sub_directories) - N_USER_KEY_STORED
        for p in path_sub_directories[:n_files_to_delete]:
            user_ids.append(p.name)
            shutil.rmtree(p)

    list_files_tmp = Path("tmp/").iterdir()
    # Delete all files related to user_id
    for file in list_files_tmp:
        for user_id in user_ids:
            if file.name.endswith(f"{user_id}.npy"):
                file.unlink()


def keygen():
    # Clean tmp directory if needed
    clean_tmp_directory()

    print("Initializing FHEModelClient...")
    task = st.session_state["task"]
    # Let's create a user_id
    user_id = numpy.random.randint(0, 2**32)
    fhe_api = FHEModelClient(f"deployment/deployment_{task}", f".fhe_keys/{user_id}")
    fhe_api.load()

    # Generate a fresh key
    fhe_api.generate_private_and_evaluation_keys(force=True)
    evaluation_key = fhe_api.get_serialized_evaluation_keys()

    numpy.save(f"tmp/tmp_evaluation_key_{user_id}.npy", evaluation_key)

    return [list(evaluation_key)[:ENCRYPTED_DATA_BROWSER_LIMIT], user_id]


def encode_quantize_encrypt(text, user_id):
    task = st.session_state["task"]
    fhe_api = FHEModelClient(f"deployment/deployment_{task}", f".fhe_keys/{user_id}")
    fhe_api.load()

    encodings = get_ECFP_AND_FEATURES(text, radius=2, bits=1024).reshape(1, -1)

    quantized_encodings = fhe_api.model.quantize_input(encodings).astype(numpy.uint8)
    encrypted_quantized_encoding = fhe_api.quantize_encrypt_serialize(encodings)

    # Save encrypted_quantized_encoding in a file, since too large to pass through regular Gradio
    # buttons, https://github.com/gradio-app/gradio/issues/1877
    numpy.save(
        f"tmp/tmp_encrypted_quantized_encoding_{user_id}.npy",
        encrypted_quantized_encoding,
    )

    # Compute size
    encrypted_quantized_encoding_shorten = list(encrypted_quantized_encoding)[
        :ENCRYPTED_DATA_BROWSER_LIMIT
    ]
    encrypted_quantized_encoding_shorten_hex = "".join(
        f"{i:02x}" for i in encrypted_quantized_encoding_shorten
    )
    return (
        encodings[0],
        quantized_encodings[0],
        encrypted_quantized_encoding_shorten_hex,
    )


def run_fhe(user_id):
    encoded_data_path = Path(f"tmp/tmp_encrypted_quantized_encoding_{user_id}.npy")
    # if not user_id:
    #     print("You need to generate FHE keys first.")
    # if not encoded_data_path.is_file():
    #     print("No encrypted data was found. Encrypt the data before trying to predict.")

    # Read encrypted_quantized_encoding from the file

    task = st.session_state["task"]
    if st.session_state["fhe_prediction"] == "":
        encrypted_quantized_encoding = numpy.load(encoded_data_path)

        # Read evaluation_key from the file
        evaluation_key = numpy.load(f"tmp/tmp_evaluation_key_{user_id}.npy")

        # Use base64 to encode the encodings and evaluation key
        encrypted_quantized_encoding = base64.b64encode(
            encrypted_quantized_encoding
        ).decode()
        encoded_evaluation_key = base64.b64encode(evaluation_key).decode()

        query = {}
        query["evaluation_key"] = encoded_evaluation_key
        query["encrypted_encoding"] = encrypted_quantized_encoding
        headers = {"Content-type": "application/json"}
        # pdb.set_trace()
        if task == "0":
            response = requests.post(
                "http://localhost:8000/predict_HLM",
                data=json.dumps(query),
                headers=headers,
            )
        elif task == "1":
            response = requests.post(
                "http://localhost:8000/predict_MDR1MDCK",
                data=json.dumps(query),
                headers=headers,
            )
        elif task == "2":
            response = requests.post(
                "http://localhost:8000/predict_SOLUBILITY",
                data=json.dumps(query),
                headers=headers,
            )
        elif task == "3":
            response = requests.post(
                "http://localhost:8000/predict_PROTEIN_BINDING_HUMAN",
                data=json.dumps(query),
                headers=headers,
            )
        elif task == "4":
            response = requests.post(
                "http://localhost:8000/predict_PROTEIN_BINDING_RAT",
                data=json.dumps(query),
                headers=headers,
            )
        elif task == "5":
            response = requests.post(
                "http://localhost:8000/predict_RLM_CLint",
                data=json.dumps(query),
                headers=headers,
            )
        else:
            print("Invalid task number")
        # pdb.set_trace()
        encrypted_prediction = base64.b64decode(response.json()["encrypted_prediction"])

        # Save encrypted_prediction in a file, since too large to pass through regular Gradio
        # buttons, https://github.com/gradio-app/gradio/issues/1877
        numpy.save(f"tmp/tmp_encrypted_prediction_{user_id}.npy", encrypted_prediction)
        encrypted_prediction_shorten = list(encrypted_prediction)[
            :ENCRYPTED_DATA_BROWSER_LIMIT
        ]
        encrypted_prediction_shorten_hex = "".join(
            f"{i:02x}" for i in encrypted_prediction_shorten
        )
        st.session_state["fhe_prediction"] = encrypted_prediction_shorten_hex

        st.session_state["fhe_done"] = True


def decrypt_prediction(user_id):
    encoded_data_path = Path(f"tmp/tmp_encrypted_prediction_{user_id}.npy")

    # Read encrypted_prediction from the file
    task = st.session_state["task"]
    if st.session_state["decryption_done"] == False:
        encrypted_prediction = numpy.load(encoded_data_path).tobytes()

        fhe_api = FHEModelClient(
            f"deployment/deployment_{task}", f".fhe_keys/{user_id}"
        )
        fhe_api.load()

        # We need to retrieve the private key that matches the client specs (see issue #18)
        fhe_api.generate_private_and_evaluation_keys(force=False)

        predictions = fhe_api.deserialize_decrypt_dequantize(encrypted_prediction)
        st.session_state["decryption_done"] = True
        st.session_state["decrypted_prediction"] = predictions


def init_session_state():
    if "molecule_submitted" not in st.session_state:
        st.session_state["molecule_submitted"] = False

    if "input_molecule" not in st.session_state:
        st.session_state["input_molecule"] = ""

    if "key_generated" not in st.session_state:
        st.session_state["key_generated"] = False

    if "evaluation_key" not in st.session_state:
        st.session_state["evaluation_key"] = []

    if "user_id" not in st.session_state:
        st.session_state["user_id"] = -100

    if "encrypt" not in st.session_state:
        st.session_state["encrypt"] = False

    if "molecule_info_list" not in st.session_state:
        st.session_state["molecule_info_list"] = []

    if "encrypt_tuple" not in st.session_state:
        st.session_state["encrypt_tuple"] = ()

    if "fhe_prediction" not in st.session_state:
        st.session_state["fhe_prediction"] = ""

    if "fhe_done" not in st.session_state:
        st.session_state["fhe_done"] = False

    if "decryption_done" not in st.session_state:
        st.session_state["decryption_done"] = False
    if "decrypted_prediction" not in st.session_state:
        st.session_state[
            "decrypted_prediction"
        ] = ""  # actually a list of list. But python takes care as it is dynamically typed.


def molecule_submitted(text: str = st.session_state.get("molecule_to_test", "")):
    msg_to_user = ""
    if len(text) == 0:
        msg_to_user = "Enter a non-empty molecule formula."
        molecule_present = False

    elif Chem.MolFromSmiles(text) == None:
        msg_to_user = "Invalid Molecule. Please enter a valid molecule. How about trying Aspirin or Ibuprofen?"
        molecule_present = False

    else:
        st.session_state["molecule_submitted"] = True
        st.session_state["input_molecule"] = text
        molecule_present = True
        msg_to_user = "Molecule Submitted for Prediction"

    st.session_state["molecule_info_list"].clear()
    st.session_state["molecule_info_list"].append(molecule_present)
    st.session_state["molecule_info_list"].append(msg_to_user)


def keygen_util():
    if st.session_state["molecule_submitted"] == False:
        pass
    else:
        if st.session_state["user_id"] == -100:
            (st.session_state["evaluation_key"], st.session_state["user_id"]) = keygen()
        st.session_state["key_generated"] = True


def encrpyt_data_util():
    if st.session_state["key_generated"] == False:
        pass
    else:
        if len(st.session_state["encrypt_tuple"]) == 0:
            st.session_state["encrypt_tuple"] = encode_quantize_encrypt(
                st.session_state["input_molecule"], st.session_state["user_id"]
            )
        st.session_state["encrypt"] = True


def mol_to_img(mol):
    mol = Chem.MolFromSmiles(mol)
    mol = AllChem.RemoveHs(mol)
    AllChem.Compute2DCoords(mol)
    drawer = rdMolDraw2D.MolDraw2DSVG(300, 300)
    drawer.DrawMolecule(mol)
    drawer.FinishDrawing()
    svg = drawer.GetDrawingText()
    return cairosvg.svg2png(bytestring=svg.encode("utf-8"))


def FHE_util():
    run_fhe(st.session_state["user_id"])


def decrypt_util():
    decrypt_prediction(st.session_state["user_id"])


def clear_session_state():
    st.session_state.clear()


# Define global variables outside main function scope.

task_options = ["0", "1", "2", "3", "4", "5"]

task_mapping = {
    "0": "HLM",
    "1": "MDR-1-MDCK-ER",
    "2": "Solubility",
    "3": "Protein bind. human",
    "4": "Protein bind. rat",
    "5": "RLM",
}

task_mapping_2 = {
    "0": "LOG HLM_CLint (mL/min/kg)",
    "1":" LOG MDR1-MDCK ER (B-A/A-B)",
    "2": "LOG SOLUBILITY PH 6.8 (ug/mL)",
    "3": "LOG PLASMA PROTEIN BINDING (HUMAN) (% unbound)",
    "4": "LOG PLASMA PROTEIN BINDING (RAT) (% unbound)",
    "5": "LOG RLM_CLint (mL/min/kg)"
}



unit_mapping = {
    "0": "(mL/min/kg)",
    "1": " ",
    "2": "(ug/mL)",
    "3": " (%)",
    "4": " (%)",
    "5": "(mL/min/kg)",
}




task_options = list(task_mapping.values())

# Create the dropdown menu
data_dict = {
    "HLM": "Human Liver Microsomes: drug is metabolized by the liver",
    "MDR-1-MDCK-ER": "MDR-1-MDCK-ER: drug is transported by the P-glycoprotein",
    "Solubility": "How soluble a drug is in water",
    "Protein bind. human": "Drug binding to human plasma proteins",
    "Protein bind. rat": "Drug binding to rat plasma proteins",
    "RLM": "Rat Liver Microsomes: Drug metabolism by a rat liver",
}

# Convert the dictionary to a DataFrame
data = pd.DataFrame(list(data_dict.items()), columns=["Property", "Explanation"])

user_id = 0

css_styling = """<style>
.table {
    width: 100%;
    margin: 10px 0 20px 0;
}
.table-striped tbody tr:nth-of-type(odd) {
    background-color: rgba(0,0,0,.05);
}
.table-hover tbody tr:hover {
    color: #563d7c;
    background-color: rgba(0,0,0,.075);
}
.table thead th, .table tbody td {
    text-align: center;
    max-width: 150px;  # Adjust this value as needed
    word-wrap: break-word;
}
</style>"""


if __name__ == "__main__":
    # Set up the Streamlit interface
    init_session_state()

    with st.container():
        st.header(":green[Start]")
        st.markdown(
            "Run all the steps in order to predict a property for a molecule of your choice. Why not all steps at once? Because we want to show you the steps involved in the process (see figure above)."
        )
        st.subheader("Step 0: Which property do you want to predict?")
        st.markdown(
            "This app can predict the following properties of confidential molecules:"
        )

        # Check if 'task' is not already in session_state
        if "task" not in st.session_state:
            # Initialize it with the first value of your options
            st.session_state["task"] = "0"

        # Custom HTML and CSS styling
        html = data.to_html(index=False, classes="table table-striped table-hover")

        # Custom styling
        st.markdown(css_styling, unsafe_allow_html=True)

        # Display the HTML table
        st.write(html, unsafe_allow_html=True)
        st.markdown("Which one do you want to predict?")
        selected_label = st.selectbox(
            "Choose a property",
            task_options,
            index=task_options.index(task_mapping[st.session_state["task"]]),
        )
        st.session_state["task"] = list(task_mapping.keys())[
            task_options.index(selected_label)
        ]

        st.subheader("Step 1: Submit a molecule")

        x, y, z = st.columns(3)

        with x:
            st.text("")

        with y:
            submit_molecule = st.button(
                "Try Aspirin",
                on_click=molecule_submitted,
                args=("CC(=O)OC1=CC=CC=C1C(=O)O",),
            )

        with z:
            submit_molecule = st.button(
                "Try Ibuprofen",
                on_click=molecule_submitted,
                args=("CC(Cc1ccc(cc1)C(C(=O)O)C)C",),
            )

        # Use the custom keyup component for text input
        molecule_to_test = st_keyup(
            label="Enter a molecular SMILES string or choose one of the two options",
            value=st.session_state.get("molecule_to_test", ""),
        )
        submit_molecule = st.button(
            "Submit",
            on_click=molecule_submitted,
            args=(molecule_to_test,),
        )

        if len(st.session_state["molecule_info_list"]) != 0:
            if st.session_state["molecule_info_list"][0] == True:
                st.success(st.session_state["molecule_info_list"][1])
                mol_image = mol_to_img(st.session_state["input_molecule"])
                # center the image
                col1, col2, col3 = st.columns([1, 2, 1])
                with col2:
                    st.image(mol_image)
                    st.caption(f"Input molecule {st.session_state['input_molecule']}")

            else:
                st.warning(st.session_state["molecule_info_list"][1], icon="⚠️")

    with st.container():
        st.subheader(
            f"Step 2 : Generate encryption key (private to you) and an evaluation key (public)."
        )
        bullet_points = """
        - Evaluation key is public and accessible by server.
        - Private Keys are solely accessible by client for encrypting the information 
        before sending to the server. The same key is used for decryption after FHE inference.
        """
        st.markdown(bullet_points, unsafe_allow_html=True)
        button_gen_key = st.button(
            "Generate Keys for this session", on_click=keygen_util
        )
        if st.session_state["key_generated"] == True:
            st.success("Keys generated successfully", icon="🙌")
            st.code(f'The user id for this session is {st.session_state["user_id"]} ')
        else:
            task = st.session_state["task"]
            task_label = task_mapping[task]
            st.warning(
                f"Please submit the molecule first to test its {task_label} value",
                icon="⚠️",
            )

    with st.container():
        st.subheader(
            f"Step 3 : Encrypt molecule using private key and send it to server."
        )
        encrypt_button = st.button("Encrypt molecule", on_click=encrpyt_data_util)
        if st.session_state["encrypt"] == True:
            st.success("Successfully Encrypted Data", icon="🙌")
            st.text("The server can only see the encrypted data:")
            st.code(
                f"The encrypted quantized encoding is \n {st.session_state['encrypt_tuple'][2]}..."
            )
        else:
            st.warning(
                "Keys Not Yet Generated. Encryption can be done only after you generate keys."
            )

    with st.container():
        st.subheader(f"Step 4 : Run encrypted prediction on server side.")
        fhe_button = st.button("Predict in FHE domain", on_click=FHE_util)
        if st.session_state["fhe_done"]:
            st.success("Prediction Done Successfuly in FHE domain", icon="🙌")
            st.code(
                f"The encrypted prediction is {st.session_state['fhe_prediction']}..."
            )
        else:
            st.warning("Check if you have generated keys correctly.")

    with st.container():
        st.subheader(f"Step 5 : Decrypt the predictions with your private key.")
        decrypt_button = st.button(
            "Perform Decryption on FHE inferred prediction", on_click=decrypt_util
        )
        if st.session_state["decryption_done"]:
            st.success("Decryption Done successfully!", icon="🙌")
            value = st.session_state["decrypted_prediction"][0][0]
            # 2 digit precision
            value = round(value, 2)
            unit = unit_mapping[st.session_state["task"]]
            task_label = task_mapping[st.session_state["task"]]
            st.code(
                f"The Molecule {st.session_state['input_molecule']} has a {task_label} value of {value} {unit}"
            )
            st.toast("Session successfully completed!!!")

            
            st.markdown("Is this a large, average or small value for this property? 🤔 Find out by comparing with the property distribution of the training dataset")
            # now load the data from the pkl
            with open("all_data.pkl", "rb") as f:
                all_data = pickle.load(f)
            import plotly.graph_objects as go

            # Assuming task_mapping_2, all_data, and 'value' are defined elsewhere in your code.

            task_label_2 = task_mapping_2[st.session_state["task"]]
            data = all_data[task_label_2]


            # Create a histogram
            fig = go.Figure(go.Histogram(x=data, nbinsx=20, marker_color='blue', opacity=0.5))

            # If you don't have specific y-values for the vertical line, you can set them to ensure the line spans the plot.
            # Here, we're assuming a static range. You might want to adjust these based on your dataset's characteristics.
            max_y_value = np.max(np.histogram(data, bins=20)[0]) # Calculate the max height of the histogram bars

            fig.add_trace(go.Scatter(x=[value, value], y=[0, max_y_value * 1.1], mode="lines", name="Threshold", line=dict(color="red", dash="dash")))

            # Update layout if necessary
            fig.update_layout(
                title="Comparison of the molecule's value with the distribution of the ADME dataset",
                xaxis_title=task_label_2,
                yaxis_title="Count",
                bargap=0.2, # Adjust the gap between bars
            )

            # Display the figure in the Streamlit app
            st.plotly_chart(fig)
        else:
            st.warning("Check if FHE computation has been done.")




    with st.container():
        st.subheader(f"Step 6 : Reset to predict a new molecule")
        reset_button = st.button("Reset app", on_click=clear_session_state)
        x, y, z = st.columns(3)
        with x:
            st.write("")
        with y:
            st.markdown(
                "<p style='text-align: center; color: grey;'>"
                + img_to_html("VaultChem.png", width="50%")
                + "</p>",
                unsafe_allow_html=True,
            )
            st.markdown(
                "<h6 style='text-align: center; color: grey;'>Visit our website : <a href='https://vaultchem.com/'>VaultChem</a></h6>",
                unsafe_allow_html=True,
            )
            st.markdown(
                "<h6 style='text-align: center; color: grey;'>Visit our Github Repo : <a href='https://github.com/vaultchem'>Github</a></h6>",
                unsafe_allow_html=True,
            )
            st.markdown(
                "<h6 style='text-align: center; color: grey;'>Built with <a href='https://streamlit.io/'>Streamlit</a>🎈</h6>",
                unsafe_allow_html=True,
            )
        with z:
            st.write("")


st.markdown(
    """
    <div style="width: 100%; text-align: center; padding: 10px;">
        The app was built with <a href="https://github.com/zama-ai/concrete-ml" target="_blank">Concrete-ML</a>,
        an open-source library by <a href="https://www.zama.ai/" target="_blank">Zama</a>.
    </div>
    """,
    unsafe_allow_html=True,
)

st.write(
    ":red[Please Note]: The content of your app is purely for educational and illustrative purposes and is not intended for the management of sensitive information. We disclaim any liability for potential financial or other damages. This platform is not a substitute for professional health advice, diagnosis, or treatment. Health-related inquiries should be directed to qualified medical professionals. Use of this app implies acknowledgment of these terms and understanding of its intended educational use."
)