merging .cool files of replicates

Question

[rls_08]

Is there a way to sum or average 2 or more .cool files corresponding to replicates in a hic experiment ?

Answer 1

[kalavattam]

This can be done with cooler and numpy, for example:

import cooler
import numpy as np
from cooler.create import create_cooler

# List of replicate .cool files
reps = ["rep_1.cool", "rep_2.cool", "rep_3.cool"]

# Open the first cooler to get bins and shape
c = cooler.Cooler(reps[0])
bins = c.bins()[:]
shape = c.shape

# Initialize sum matrix
sum_mat = np.zeros(shape, dtype=np.float64)

# Loop through .cool files and sum matrices
for cf in reps:
    c = cooler.Cooler(cf)

    # Ensure resolution consistency
    assert c.shape == shape, f"Resolution mismatch in {cf}"

    # Convert NaNs to 0 before summing
    mat = c.matrix(balance=False)[:]
    mat = np.nan_to_num(mat, nan=0)
    sum_mat += mat

# Convert summed matrix to cooler-compatible pixel format
pixels = np.column_stack(np.where(sum_mat > 0))
counts = sum_mat[pixels[:, 0], pixels[:, 1]]

# Save summed matrix
create_cooler(
    "summed.cool",
    bins,
    {"bin1_id": pixels[:, 0], "bin2_id": pixels[:, 1], "count": counts}
)

# Compute and save averaged matrix
avg_mat = sum_mat / len(reps)
counts = avg_mat[pixels[:, 0], pixels[:, 1]]

create_cooler(
    "average.cool",
    bins,
    {"bin1_id": pixels[:, 0], "bin2_id": pixels[:, 1], "count": counts}
)

print("Summed and averaged .cool files saved.")

Note: I converted NaN values to zeroes, which may not be ideal.