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name: hic-tad-calling description: This skill should be used when users need to identify topologically associating domains (TADs) from Hi-C data in .mcools (or .cool) files or when users want to visualize the TAD in target genome loci. It provides workflows for TAD calling and visualization.

TADs Calling with HiCExplorer and Cooltools

Overview

This skill enables comprehensive identification and analysis of topologically associating domains (TADs) from Hi-C data stored in .mcool (or .cool) files. It integrates HiCExplorer for robust TAD calling and visualization capabilities.

Main steps include:

• Refer to the Inputs & Outputs section to verify required files and output structure.
• Data Preparation: Ensure .mcool files are formatted correctly and resolutions are verified.
• Always prompt user for resolution used to call TADs.
• TAD Calling: Use HiCExplorer to call TADs with customizable parameters.
• Always prompt user for target genomic loci for visualization.
• Visualization: Generate contact maps with TAD boundaries overlayed, for specific regions of the genome.

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When to use this skill

Use this skill when:

• You need to identify TADs in Hi-C data stored in .mcool (or .cool) files.
• You want to visualize TADs in a specific region of the genome.
• You need to perform automated TAD calling with HiCExplorer, including statistical corrections.

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Inputs & Outputs

Inputs

• File format: .mcool, .cool, or .hic (Hi-C data file).
• Resolution: Provided by user. ~10-50 kb is recommended. Default is 50 kb. 25 kb is the best but memory-consuming.
• Target region: Genome region provided by user to visualize TADs (e.g., "chr22:1000000-2000000").

Outputs

${sample}_TAD_calling/
    TADs/
        ${sample}_TAD_boundaries.bed  # Called TADs in BED format
        ${sample}_TAD_boundaries.gff
        ${sample}_TAD_domains.bed
        ... # other files output by the hicFindTADs
    plots/
        ${sample}_TADs_${genome_loci}.pdf  # TADs visualization (contact map)
    temp/
        ${sample}_track.ini            # Configuration file for visualization

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Allowed Tools

When using this skill, you should restrict yourself to the following MCP tools from server cooler-tools, cooltools-tools, project-init-tools, genome-locate-tools:

• mcp__project-init-tools__project_init
• mcp__genome-locate-tools__genome_locate_fasta
• mcp__HiCExplorer-tools__hic_to_mcool
• mcp__HiCExplorer-tools__check_mcool_file
• mcp__HiCExplorer-tools__run_hicFindTADs
• mcp__HiCExplorer-tools__generate_track_ini
• mcp__HiCExplorer-tools__plot_tads_region

Do NOT fall back to:

• raw shell commands (hicFindTADs, hicPlotTADs, etc.)
• ad-hoc Python snippets (e.g. importing cooler, bioframe, matplotlib manually in the reply).

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Decision Tree

Step 0 — Gather Required Information from the User

Before calling any tool, ask the user:

1. Sample name (sample): used as prefix and for the output directory ${sample}_TAD_calling.
2. Genome assembly (genome): e.g. hg38, mm10, danRer11.
   • Never guess or auto-detect.
3. Hi-C matrix path/URI (mcool_uri): e.g. .mcool file path or .hic file path.
   • path/to/sample.mcool::/resolutions/50000 (.mcool file with resolution specified)
   • or .cool file path
   • or .hic file path
4. Resolution (resolution): default 50000 (50 kb).
   • If user does not specify, use 50000 as default.
   • Must be the same as the resolution used for ${mcool_uri}

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Step 1: Initialize Project

1. Make director for this project:

Call:

• mcp__project-init-tools__project_init

with:

• sample: the user-provided sample name
• task: TAD_calling

The tool will:

• Create ${sample}_TAD_calling directory.
• Get the full path of the ${sample}_TAD_calling directory, which will be used as ${proj_dir}.

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2. If the user provides a .hic file, convert it to .mcool file first using mcp__HiCExplorer-tools__hic_to_mcool tool:

Call:

• mcp__HiCExplorer-tools__hic_to_mcool

with:

• input_hic: the user-provided path (e.g. input.hic)
• sample: the user-provided sample name
• proj_dir: directory to save the view file. In this skill, it is the full path of the ${sample}_TAD_calling directory returned by mcp__project-init-tools__project_init.
• resolutions: the user-provided resolutions (e.g. [50000])

The tool will:

• Convert the .hic file to .mcool file.
• Return the path of the .mcool file.

If the conversion is successful, update ${mcool_uri} to the path of the .mcool file.

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3. Inspect the .mcool file to list available resolutions and confirm the analysis resolution with the user.

Call:

• mcp__cooler-tools__list_mcool_resolutions

with:

• mcool_path: the user-provided path (e.g. input.mcool) or the path of the .mcool file returned by mcp__HiCExplorer-tools__hic_to_mcool

The tool will:

• List all resolutions in the .mcool file.
• Return the resolutions as a list.

If the ${resolution} is not found, ask the user to specify the resolution again. Else, use ${resolution}.

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Step 2: HiCExplorer TAD Calling

Use mcp__HiCExplorer-tools__run_hicFindTADs for comprehensive TAD identification. Customize parameters to suit the resolution and depth of your Hi-C data: Before calling the tool, ask the user for the following parameters:

• ${min_depth}: Minimum window size (e.g. 3x resolution, default 150000, must be at least 3 times larger than the resolution)
• ${max_depth}: Maximum window size (e.g. 6-10x resolution, default 300000, must be at least 5 times larger than the resolution)
• ${step}: Step size for sliding window (default 50000, 25000 is the best but memory-consuming)
• ${multiple_testing}: Multiple testing correction method (e.g. 'fdr')
• ${threshold_comparisons}: FDR threshold for significant TADs (default 0.05)
• ${delta}: Delta parameter for TAD boundary detection (default 0.01)
• ${chromosomes}: Chromosomes to call TADs (default chr22). It is suggested to call TADs on a certain chromosome because it is memory-consuming to call TADs on all chromosomes and this process would likely be killed by the system.

Call:

• mcp__HiCExplorer-tools__run_hicFindTADs with:
• sample: ${sample}
• proj_dir: directory to save the view file. In this skill, it is the full path of the ${sample}_TAD_calling directory returned by mcp__project-init-tools__project_init.
• mcool_uri: cooler URI with resolution specified, e.g. input.mcool::/resolutions/${resolution}
• resolution: ${resolution} must be the same as the resolution used for ${mcool_uri} and must be an integer
• min_depth: ${min_depth}, must be at least 3 times larger than the resolution.
• max_depth: ${max_depth}, must be at least 5 times larger than the resolution. step: ${step}
• multiple_testing: ${multiple_testing}
• threshold_comparisons: ${threshold_comparisons}
• delta: ${delta}
• chromosomes: chromosomes to call TADs, e.g. chr22, space-separated list.

The tool will:

• Call mcp__HiCExplorer-tools__run_hicFindTADs to identify TADs.
• Return the path of the TADs file under ${proj_dir}/TADs/ directory.

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Step 3: Visualization

1. generate the <track.ini> file first for visualization

Call:

• mcp__HiCExplorer-tools__generate_track_ini

with:

• sample: ${sample}
• proj_dir: directory to save the view file. In this skill, it is the full path of the ${sample}_TAD_calling directory returned by mcp__project-init-tools__project_init.
• mcool_uri: cooler URI with resolution specified, e.g. input.mcool::/resolutions/${resolution}
• resolution: ${resolution} must be the same as the resolution used for ${mcool_uri} and must be an integer
• depth: depth for the Hi-C matrix view, e.g. 1500000
• min_value: minimum value for the Hi-C matrix view, e.g. 0.0
• max_value: maximum value for the Hi-C matrix view, e.g. 80.0

The tool will:

• Generate the <track.ini> file under ${proj_dir}/temp/ directory.
• Return the path of the <track.ini> file.

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2. Contact Maps with TAD Overlays Before calling the tool, ask the user for the target region, like "chr22:1000000-2000000".

Call:

• mcp__HiCExplorer-tools__plot_tads_region

with:

• sample: ${sample}
• proj_dir: directory to save the view file. In this skill, it is the full path of the ${sample}_TAD_calling directory returned by mcp__project-init-tools__project_init.
• region: user-provided target region, like "chr22:1000000-2000000"
• dpi: dpi for the contact map, default is 300

The tool will:

• Generate the contact map with TAD boundaries overlayed.
• Return the path of the contact map file under ${proj_dir}/plots/ directory.

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Best Practices

• It is suggested to call TADs on a certain chromosome because it is memory-consuming to call TADs on all chromosomes and this process would likely be killed by the system.