Agent skill

bio-hi-c-analysis-hic-visualization

Visualize Hi-C contact matrices, TADs, loops, and genomic features using matplotlib, cooltools, and HiCExplorer. Create triangle plots, virtual 4C, and multi-track figures. Use when visualizing contact matrices or genomic features.

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Install this agent skill to your Project

npx add-skill https://github.com/FreedomIntelligence/OpenClaw-Medical-Skills/tree/main/skills/bio-hi-c-analysis-hic-visualization

SKILL.md

Version Compatibility

Reference examples tested with: cooler 0.9+, cooltools 0.6+, matplotlib 3.8+, numpy 1.26+, pandas 2.2+

Before using code patterns, verify installed versions match. If versions differ:

  • Python: pip show <package> then help(module.function) to check signatures
  • CLI: <tool> --version then <tool> --help to confirm flags

If code throws ImportError, AttributeError, or TypeError, introspect the installed package and adapt the example to match the actual API rather than retrying.

Hi-C Visualization

"Plot my Hi-C contact matrix" → Create triangle heatmaps, virtual 4C profiles, and multi-track figures combining contact maps with genomic annotations.

  • Python: matplotlib.pyplot.imshow() on cooler matrices, cooltools for aggregate plots
  • CLI: hicPlotMatrix (HiCExplorer)

Visualize Hi-C contact matrices and genomic features.

Required Imports

python
import cooler
import cooltools
import cooltools.lib.plotting
import numpy as np
import matplotlib.pyplot as plt
from matplotlib.colors import LogNorm
import bioframe

Basic Contact Matrix Plot

python
clr = cooler.Cooler('matrix.mcool::resolutions/10000')

# Get matrix for a region
matrix = clr.matrix(balance=True).fetch('chr1:50000000-60000000')

fig, ax = plt.subplots(figsize=(8, 8))
im = ax.imshow(matrix, cmap='Reds', norm=LogNorm(vmin=0.001, vmax=0.1))
plt.colorbar(im, ax=ax, label='Balanced contacts')
ax.set_title('chr1:50-60Mb')
plt.savefig('contact_matrix.png', dpi=150)

Triangle (Upper Triangle) Plot

python
def plot_triangle(matrix, ax, cmap='Reds', vmin=None, vmax=None):
    '''Plot Hi-C matrix as triangle (rotated 45 degrees)'''
    n = matrix.shape[0]

    # Create rotated matrix
    rotated = np.zeros((n, 2*n))
    for i in range(n):
        for j in range(i, n):
            y = j - i
            x = i + j
            rotated[y, x] = matrix[i, j]

    # Plot
    im = ax.imshow(rotated[:n//2, :], cmap=cmap, aspect='auto',
                   norm=LogNorm(vmin=vmin, vmax=vmax) if vmin else None)
    ax.set_ylim(n//2, 0)
    return im

matrix = clr.matrix(balance=True).fetch('chr1:50000000-60000000')
fig, ax = plt.subplots(figsize=(12, 4))
im = plot_triangle(matrix, ax, vmin=0.001, vmax=0.1)
plt.colorbar(im, ax=ax)
plt.savefig('triangle_plot.png', dpi=150)

Plot with TADs

python
import pandas as pd

matrix = clr.matrix(balance=True).fetch('chr1:50000000-60000000')
tads = pd.read_csv('tads.bed', sep='\t', names=['chrom', 'start', 'end'])

fig, ax = plt.subplots(figsize=(8, 8))
im = ax.imshow(matrix, cmap='Reds', norm=LogNorm(vmin=0.001, vmax=0.1))

# Overlay TAD boundaries
region_start = 50000000
bin_size = clr.binsize
for _, tad in tads[tads['chrom'] == 'chr1'].iterrows():
    if region_start <= tad['start'] < 60000000:
        pos = (tad['start'] - region_start) / bin_size
        ax.axhline(pos, color='blue', linewidth=0.5, alpha=0.5)
        ax.axvline(pos, color='blue', linewidth=0.5, alpha=0.5)

plt.colorbar(im, ax=ax)
plt.savefig('matrix_with_tads.png', dpi=150)

Plot with Loops

python
matrix = clr.matrix(balance=True).fetch('chr1:50000000-60000000')
loops = pd.read_csv('loops.bedpe', sep='\t')

fig, ax = plt.subplots(figsize=(8, 8))
im = ax.imshow(matrix, cmap='Reds', norm=LogNorm(vmin=0.001, vmax=0.1))

# Mark loops
region_start = 50000000
bin_size = clr.binsize
for _, loop in loops[loops['chrom1'] == 'chr1'].iterrows():
    if (region_start <= loop['start1'] < 60000000 and
        region_start <= loop['start2'] < 60000000):
        x = (loop['start1'] - region_start) / bin_size
        y = (loop['start2'] - region_start) / bin_size
        circle = plt.Circle((y, x), 3, fill=False, color='blue', linewidth=1)
        ax.add_patch(circle)

plt.colorbar(im, ax=ax)
plt.savefig('matrix_with_loops.png', dpi=150)

Compare Two Matrices

python
clr1 = cooler.Cooler('sample1.mcool::resolutions/10000')
clr2 = cooler.Cooler('sample2.mcool::resolutions/10000')

region = 'chr1:50000000-60000000'
mat1 = clr1.matrix(balance=True).fetch(region)
mat2 = clr2.matrix(balance=True).fetch(region)

fig, axes = plt.subplots(1, 3, figsize=(15, 5))

# Sample 1
im1 = axes[0].imshow(mat1, cmap='Reds', norm=LogNorm(vmin=0.001, vmax=0.1))
axes[0].set_title('Sample 1')
plt.colorbar(im1, ax=axes[0])

# Sample 2
im2 = axes[1].imshow(mat2, cmap='Reds', norm=LogNorm(vmin=0.001, vmax=0.1))
axes[1].set_title('Sample 2')
plt.colorbar(im2, ax=axes[1])

# Log2 fold change
log2fc = np.log2(mat2 / mat1)
log2fc[np.isinf(log2fc)] = np.nan
im3 = axes[2].imshow(log2fc, cmap='coolwarm', vmin=-2, vmax=2)
axes[2].set_title('Log2(Sample2/Sample1)')
plt.colorbar(im3, ax=axes[2])

plt.tight_layout()
plt.savefig('comparison.png', dpi=150)

Split View (Upper/Lower Triangle)

python
mat1 = clr1.matrix(balance=True).fetch(region)
mat2 = clr2.matrix(balance=True).fetch(region)

# Combine: upper triangle from mat1, lower from mat2
combined = np.triu(mat1) + np.tril(mat2, k=-1)

fig, ax = plt.subplots(figsize=(8, 8))
im = ax.imshow(combined, cmap='Reds', norm=LogNorm(vmin=0.001, vmax=0.1))
ax.axline((0, 0), slope=1, color='black', linewidth=0.5)
ax.set_title('Sample1 (upper) vs Sample2 (lower)')
plt.colorbar(im, ax=ax)
plt.savefig('split_view.png', dpi=150)

Virtual 4C

Goal: Extract a one-dimensional contact frequency profile from a single viewpoint locus, simulating a 4C experiment from Hi-C data.

Approach: Select the matrix row corresponding to the viewpoint bin, extract balanced contact values across the chromosome, and plot as a filled line graph.

python
def virtual_4c(clr, viewpoint_chrom, viewpoint_pos, resolution=10000):
    '''Extract virtual 4C from Hi-C'''
    # Get row of matrix at viewpoint
    viewpoint_bin = viewpoint_pos // resolution

    # Get contacts from this bin to all others on same chromosome
    matrix = clr.matrix(balance=True).fetch(viewpoint_chrom)
    v4c = matrix[viewpoint_bin, :]

    # Create coordinates
    bins = clr.bins().fetch(viewpoint_chrom)
    coords = bins['start'].values

    return coords, v4c

coords, v4c = virtual_4c(clr, 'chr1', 55000000)

fig, ax = plt.subplots(figsize=(12, 3))
ax.fill_between(coords / 1e6, 0, v4c, alpha=0.5)
ax.axvline(55, color='red', linestyle='--', label='Viewpoint')
ax.set_xlabel('Position (Mb)')
ax.set_ylabel('Contact frequency')
ax.set_title('Virtual 4C from chr1:55Mb')
ax.legend()
plt.savefig('virtual_4c.png', dpi=150)

Multi-Track Figure

python
fig = plt.figure(figsize=(12, 10))

# Hi-C matrix (triangle)
ax1 = fig.add_axes([0.1, 0.5, 0.8, 0.4])
matrix = clr.matrix(balance=True).fetch('chr1:50000000-60000000')
plot_triangle(matrix, ax1, vmin=0.001, vmax=0.1)
ax1.set_ylabel('Hi-C')

# Insulation score
ax2 = fig.add_axes([0.1, 0.35, 0.8, 0.1])
insulation = pd.read_csv('insulation.bedgraph', sep='\t',
                         names=['chrom', 'start', 'end', 'score'])
ins_region = insulation[(insulation['chrom'] == 'chr1') &
                        (insulation['start'] >= 50000000) &
                        (insulation['end'] <= 60000000)]
ax2.plot(ins_region['start'] / 1e6, ins_region['score'])
ax2.set_ylabel('Insulation')
ax2.set_xlim(50, 60)

# Gene track (placeholder)
ax3 = fig.add_axes([0.1, 0.2, 0.8, 0.1])
ax3.set_ylabel('Genes')
ax3.set_xlim(50, 60)

# CTCF ChIP-seq (placeholder)
ax4 = fig.add_axes([0.1, 0.05, 0.8, 0.1])
ax4.set_xlabel('Position (Mb)')
ax4.set_ylabel('CTCF')
ax4.set_xlim(50, 60)

plt.savefig('multi_track.png', dpi=150)

Using HiCExplorer Visualization

bash
# Plot matrix with HiCExplorer
hicPlotMatrix \
    -m matrix.cool \
    --region chr1:50000000-60000000 \
    --log1p \
    --colorMap Reds \
    -o hic_plot.png

# Plot with TADs
hicPlotTADs \
    --tracks tracks.ini \
    --region chr1:50000000-60000000 \
    -o tad_plot.png

Cooltools Pileup Plot

python
import cooltools

# Pileup at features (e.g., loop anchors)
pileup = cooltools.pileup(
    clr,
    features=loops[['chrom1', 'start1', 'end1', 'chrom2', 'start2', 'end2']],
    view_df=view_df,
    expected=expected,
    flank=100000,
)

# Average pileup
avg_pileup = np.nanmean(pileup, axis=2)

fig, ax = plt.subplots(figsize=(6, 6))
im = ax.imshow(avg_pileup, cmap='Reds')
ax.set_title('Average pileup at loops')
plt.colorbar(im, ax=ax)
plt.savefig('pileup.png', dpi=150)

Related Skills

  • hic-data-io - Load contact matrices
  • tad-detection - Generate TADs to visualize
  • loop-calling - Generate loops to visualize
  • compartment-analysis - Visualize compartments

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