cluster_landscapes_v3.py

import pandas as pd
import numpy as np
from transformers import EsmModel, AutoTokenizer
import torch
from scipy.spatial.distance import pdist, squareform
from gudhi import RipsComplex
from gudhi.representations.vector_methods import Landscape
from sklearn.cluster import DBSCAN
# import matplotlib.pyplot as plt
from tqdm import tqdm

# Define a helper function for hidden states
def get_hidden_states(sequence, tokenizer, model, layer):
    model.config.output_hidden_states = True
    encoded_input = tokenizer([sequence], return_tensors='pt', padding=True, truncation=True, max_length=1024)
    with torch.no_grad():
        model_output = model(**encoded_input)
    hidden_states = model_output.hidden_states
    specific_hidden_states = hidden_states[layer][0]
    return specific_hidden_states.numpy()

# Define a helper function for Euclidean distance matrix
def compute_euclidean_distance_matrix(hidden_states):
    euclidean_distances = pdist(hidden_states, metric='euclidean')
    euclidean_distance_matrix = squareform(euclidean_distances)
    return euclidean_distance_matrix

# Define a helper function for persistent homology
def compute_persistent_homology(distance_matrix, max_dimension=0):
    max_edge_length = np.max(distance_matrix)
    rips_complex = RipsComplex(distance_matrix=distance_matrix, max_edge_length=max_edge_length)
    st = rips_complex.create_simplex_tree(max_dimension=max_dimension)
    st.persistence()
    persistence_pairs = np.array([[p[1][0], p[1][1]] for p in st.persistence() if p[0] == 0 and p[1][1] < np.inf])  # Filter out infinite death times
    return st, persistence_pairs

# Define a helper function for persistent homology
def compute_persistent_homology2(distance_matrix, max_dimension=0):
    max_edge_length = np.max(distance_matrix)
    rips_complex = RipsComplex(distance_matrix=distance_matrix, max_edge_length=max_edge_length)
    st = rips_complex.create_simplex_tree(max_dimension=max_dimension)
    st.persistence()
    return st, st.persistence()

# Define a helper function for Landscape transformations with tqdm
#def compute_landscapes(persistence_diagrams, num_landscapes=5, resolution=10000):
#    landscape_transformer = Landscape(num_landscapes=num_landscapes, resolution=resolution)
#    landscapes = landscape_transformer.fit_transform([d for d in persistence_diagrams if len(d) > 0])  # Filter out empty diagrams
#    return landscapes

def compute_landscapes(persistence_diagrams, num_landscapes=5, resolution=10000):
    landscape_transformer = Landscape(num_landscapes=num_landscapes, resolution=resolution)
    landscapes = []

    for diagram in tqdm(persistence_diagrams, desc="Computing Landscapes"):
        if len(diagram) > 0:
            landscape = landscape_transformer.fit_transform([diagram])[0]
            landscapes.append(landscape)

    return landscapes

# Load the tokenizer and model
tokenizer = AutoTokenizer.from_pretrained("facebook/esm2_t33_650M_UR50D")
model = EsmModel.from_pretrained("facebook/esm2_t33_650M_UR50D")

# Define layer to be used
layer = model.config.num_hidden_layers - 1

# Load the TSV file
file_path = 'clustering_and_evoprotgrad/filtered_protein_interaction_pairs.tsv'
protein_pairs_df = pd.read_csv(file_path, sep='\t')

# Only process the first 1000 proteins
protein_pairs_df = protein_pairs_df.head(10000)

# Extract concatenated sequences
concatenated_sequences = protein_pairs_df['Protein1'] + protein_pairs_df['Protein2']

# Initialize list to store persistent diagrams
persistent_diagrams = []

# Loop over concatenated sequences to compute their persistent diagrams
for sequence in tqdm(concatenated_sequences, desc="Computing Persistence Diagrams"):
    hidden_states_matrix = get_hidden_states(sequence, tokenizer, model, layer)
    distance_matrix = compute_euclidean_distance_matrix(hidden_states_matrix)
    _, persistence_diagram = compute_persistent_homology(distance_matrix)
    persistent_diagrams.append(persistence_diagram)

# Compute landscapes
landscapes = compute_landscapes(persistent_diagrams)

# Compute the L2 distances between landscapes
with tqdm(total=len(landscapes)*(len(landscapes)-1)//2, desc="Computing Pairwise L2 Distances") as pbar:
    l2_distances = np.zeros((len(landscapes), len(landscapes)))
    for i in range(len(landscapes)):
        for j in range(i+1, len(landscapes)):
            l2_distances[i, j] = l2_distances[j, i] = np.linalg.norm(landscapes[i] - landscapes[j])
            pbar.update(1)

# Compute the second-level persistent homology using the L2 distance matrix
with tqdm(total=1, desc="Computing Second-Level Persistent Homology") as pbar:
    st_2, persistence_2 = compute_persistent_homology2(l2_distances)
    pbar.update(1)

# Function to calculate the epsilon for DBSCAN
def calculate_epsilon(persistence_diagrams, threshold_percentage, max_eps=np.inf):
    lifetimes = [p[1][1] - p[1][0] for p in persistence_diagrams if p[0] == 0]
    lifetimes.sort()
    threshold_index = int(threshold_percentage * len(lifetimes))
    epsilon = lifetimes[threshold_index]
    # Ensure epsilon is within a reasonable range
    epsilon = min(epsilon, max_eps)
    return epsilon

# Calculate epsilon with a maximum threshold
threshold_percentage = 0.35  # 50%
max_epsilon = 5000.0  # Example maximum threshold
epsilon = calculate_epsilon(persistence_2, threshold_percentage, max_eps=max_epsilon)

# Perform DBSCAN clustering
with tqdm(total=1, desc="Performing DBSCAN Clustering") as pbar:
    dbscan = DBSCAN(metric="precomputed", eps=epsilon, min_samples=1)
    dbscan.fit(l2_distances)  # Use L2 distances here
    labels = dbscan.labels_
    pbar.update(1)

# Add the cluster labels to the DataFrame
protein_pairs_df['Cluster'] = labels

# Save the DataFrame with cluster information
output_file_path = 'clustering_and_evoprotgrad/clustered_protein_pair_landscapes_l2_dist_100K.tsv'
protein_pairs_df.to_csv(output_file_path, sep='\t', index=False)

print(f"Clustered data saved to: {output_file_path}")