app.py

import streamlit as st
import numpy as np
import pandas as pd
import pickle
import pygad

from VQGAE.models import VQGAE, OrderingNetwork
from CGRtools.containers import QueryContainer
from VQGAE.utils import frag_counts_to_inds, restore_order, decode_molecules

# define groups to filter
allene = QueryContainer()
allene.add_atom("C")
allene.add_atom("A")
allene.add_atom("A")
allene.add_bond(1, 2, 2)
allene.add_bond(1, 3, 2)

peroxide_charge = QueryContainer()
peroxide_charge.add_atom("O", charge=-1)
peroxide_charge.add_atom("O")
peroxide_charge.add_bond(1, 2, 1)

peroxide = QueryContainer()
peroxide.add_atom("O")
peroxide.add_atom("O")
peroxide.add_bond(1, 2, 1)


def tanimoto_kernel(x, y):
    """
    "The Tanimoto coefficient is a measure of the similarity between two sets.
    It is defined as the size of the intersection divided by the size of the union of the sample sets."

    The Tanimoto coefficient is also known as the Jaccard index

    Adoppted from https://github.com/cimm-kzn/CIMtools/blob/master/CIMtools/metrics/pairwise.py

    :param x: 2D array of features.
    :param y: 2D array of features.
    :return: The Tanimoto coefficient between the two arrays.
    """
    x_dot = np.dot(x, y.T)

    x2 = (x ** 2).sum(axis=1)
    y2 = (y ** 2).sum(axis=1)

    len_x2 = len(x2)
    len_y2 = len(y2)

    result = x_dot / (np.array([x2] * len_y2).T + np.array([y2] * len_x2) - x_dot)
    result[np.isnan(result)] = 0

    return result


def fitness_func_batch(ga_instance, solutions, solutions_indices):
    frag_counts = np.array(solutions)
    if len(frag_counts.shape) == 1:
        frag_counts = frag_counts[np.newaxis, :]

    # prediction of activity by random forest
    rf_score = rf_model.predict_proba(frag_counts)[:, 1]

    # size penalty if molecule too small
    mol_size = frag_counts.sum(-1).astype(np.int64)
    size_penalty = np.where(mol_size < 18, -1.0, 0.)

    # adding dissimilarity so it generates different solutions
    dissimilarity_score = 1 - tanimoto_kernel(frag_counts, X).max(-1)
    dissimilarity_score += np.where(dissimilarity_score == 0, -5, 0)

    # full fitness function
    fitness = 0.5 * rf_score + 0.3 * dissimilarity_score + size_penalty

    # prediction of ordering score
    if use_ordering_score:
        frag_inds = frag_counts_to_inds(frag_counts, max_atoms=51)
        _, ordering_scores = restore_order(frag_inds, ordering_model)
        ordering_scores = np.array(ordering_scores)
        fitness += 0.2 * ordering_scores

    return fitness.tolist()


def on_generation_progress(ga):
    global ga_progress
    global ga_bar
    ga_progress = ga_progress + 1
    ga_bar.progress(ga_progress // num_generations * 100, text=ga_progress_text)


@st.cache_data
def load_data(batch_size):
    X = np.load("saved_model/tubulin_qsar_class_train_data_vqgae.npz")["x"]
    Y = np.load("saved_model/tubulin_qsar_class_train_data_vqgae.npz")["y"]
    with open("saved_model/rf_class_train_tubulin.pickle", "rb") as inp:
        rf_model = pickle.load(inp)

    vqgae_model = VQGAE.load_from_checkpoint(
        "saved_model/vqgae.ckpt",
        task="decode",
        batch_size=batch_size,
        map_location="cpu"
    )
    vqgae_model = vqgae_model.eval()

    ordering_model = OrderingNetwork.load_from_checkpoint(
        "saved_model/ordering_network.ckpt",
        batch_size=batch_size,
        map_location="cpu"
    )
    ordering_model = ordering_model.eval()
    return X, Y, rf_model, vqgae_model, ordering_model

st.title('Inverse QSAR of Tubulin inhibitors in colchicine site with VQGAE')

batch_size = 500
X, Y, rf_model, vqgae_model, ordering_model = load_data(batch_size)

assert X.shape == (603, 4096)

with st.sidebar:
    with st.form("my_form"):
        num_generations = st.slider(
            'Number of generations for GA',
            min_value=3,
            max_value=40,
            value=5
        )

        parent_selection_type = st.selectbox(
            label='Parent selection type',
            options=(
                'Steady-state selection',
                'Roulette wheel selection',
                'Stochastic universal selection',
                'Rank selection',
                'Random selection',
                'Tournament selection'
            ),
            index=1
        )

        parent_selection_translator = {
            "Steady-state selection": "sss",
            "Roulette wheel selection": "rws",
            "Stochastic universal selection": "sus",
            "Rank selection": "rank",
            "Random selection": "random",
            "Tournament selection": "tournament",
        }

        parent_selection_type = parent_selection_translator[parent_selection_type]

        crossover_type = st.selectbox(
            label='Crossover type',
            options=(
                'Single point',
                'Two points',
            ),
            index=0
        )

        crossover_translator = {
            "Single point": "single_point",
            "Two points": "two_points",
        }

        crossover_type = crossover_translator[crossover_type]

        num_parents_mating = st.slider(
            'Pecentage of parents mating taken from initial population',
            min_value=0,
            max_value=X.shape[0],
            step=0.01,
            value=0.33,
        ) * X.shape[0] * 10 // 10

        keep_parents = st.slider(
            'Percentage of parents kept taken from number of parents mating',
            min_value=1,
            max_value=num_parents_mating,
            value=int(num_parents_mating * 0.66 // 10 * 10) # 2/3 of num_parents_mating
        )

        use_ordering_score = st.toggle('Use ordering score', value=True)

        random_seed = int(st.number_input("Random seed", value=42, placeholder="Type a number..."))
        st.form_submit_button('Start optimisation')

ga_instance = pygad.GA(
    fitness_func=fitness_func_batch,
    on_generation=on_generation_progress,
    initial_population=X,
    num_genes=X.shape[-1],
    fitness_batch_size=batch_size,
    num_generations=num_generations,
    num_parents_mating=num_parents_mating,
    parent_selection_type=parent_selection_type,
    crossover_type=crossover_type,
    mutation_type="adaptive",
    mutation_percent_genes=[10, 5],
    # https://pygad.readthedocs.io/en/latest/pygad.html#use-adaptive-mutation-in-pygad
    save_best_solutions=False,
    save_solutions=True,
    keep_elitism=0,  # turn it off to make keep_parents work
    keep_parents=keep_parents,
    suppress_warnings=True,
    random_seed=random_seed,
    gene_type=int
)

ga_progress = 0
ga_progress_text = "Genetic optimisation in progress. Please wait."
ga_bar = st.progress(ga_progress // num_generations * 100, text=ga_progress_text)
ga_instance.run()

with st.spinner('Getting unique solutions'):
    unique_solutions = list(set(tuple(s) for s in ga_instance.solutions))
st.success(f'{len(unique_solutions)} solutions were obtained')

scores = {
    "rf_score": [],
    "similarity_score": []
}

if use_ordering_score:
    scores["ordering_score"] = []

rescoring_progress = 0
rescoring_progress_text = "Rescoring obtained solutions"
rescoring_bar = st.progress(0, text=rescoring_progress_text)
total_rescoring_steps = len(unique_solutions) // batch_size + 1
for i in range(total_rescoring_steps):
    vqgae_latents = unique_solutions[i * batch_size: (i + 1) * batch_size]
    frag_counts = np.array(vqgae_latents)
    rf_scores = rf_model.predict_proba(frag_counts)[:, 1]
    similarity_scores = tanimoto_kernel(frag_counts, X).max(-1)
    scores["rf_score"].extend(rf_scores.tolist())
    scores["similarity_score"].extend(similarity_scores.tolist())
    if use_ordering_score:
        frag_inds = frag_counts_to_inds(frag_counts, max_atoms=51)
        _, ordering_scores = restore_order(frag_inds, ordering_model)
        scores["ordering_score"].extend(ordering_scores)
    rescoring_bar.progress(i // total_rescoring_steps * 100, text=rescoring_progress_text)

sc_df = pd.DataFrame(scores)

if use_ordering_score:
    chosen_gen = sc_df[(sc_df["similarity_score"] < 0.95) & (sc_df["rf_score"] > 0.5) & (sc_df["ordering_score"] > 0.7)]
else:
    chosen_gen = sc_df[
        (sc_df["similarity_score"] < 0.95) & (sc_df["rf_score"] > 0.5)]

chosen_ids = chosen_gen.index.to_list()
chosen_solutions = np.array([unique_solutions[ind] for ind in chosen_ids])
gen_frag_inds = frag_counts_to_inds(chosen_solutions, max_atoms=51)
st.info(f'The number of chosen solutions is {gen_frag_inds.shape[0]}', icon="ℹ️")

gen_molecules = []
results = {"smiles": [], "ordering_score": [], "validity": []}
decoding_progress = 0
decoding_progress_text = "Decoding chosen solutions"
decoding_bar = st.progress(0, text=decoding_progress_text)
total_decoding_steps = gen_frag_inds.shape[0] // batch_size + 1
for i in range(total_decoding_steps):
    inputs = gen_frag_inds[i * batch_size: (i + 1) * batch_size]
    canon_order_inds, scores = restore_order(
        frag_inds=inputs,
        ordering_model=ordering_model,
    )
    molecules, validity = decode_molecules(
        ordered_frag_inds=canon_order_inds,
        vqgae_model=vqgae_model
    )
    gen_molecules.extend(molecules)
    results["smiles"].extend([str(molecule) for molecule in molecules])
    results["ordering_score"].extend(scores)
    results["validity"].extend([1 if i else 0 for i in validity])
    decoding_bar.progress(i // total_decoding_steps * 100, text=rescoring_progress_text)

gen_stats = pd.DataFrame(results)
full_stats = pd.concat([gen_stats, chosen_gen[["similarity_score", "rf_score"]].reset_index(), ], axis=1, ignore_index=False)

st.dataframe(full_stats)

# valid_gen_stats = full_stats[full_stats.valid == 1]
#
# valid_gen_mols = []
# for i, record in zip(list(valid_gen_stats.index), valid_gen_stats.to_dict("records")):
#     mol = gen_molecules[i]
#     valid_gen_mols.append(mol)
#
# filtered_gen_mols = []
# for mol in valid_gen_mols:
#     is_frag = allene < mol or peroxide_charge < mol or peroxide < mol
#     is_macro = False
#     for ring in mol.sssr:
#         if len(ring) > 8 or len(ring) < 4:
#             is_macro = True
#             break
#     if not is_frag and not is_macro:
#         filtered_gen_mols.append(mol)