# Hic Tad Calling > 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. - Skill: `diegosouzapw/hic-tad-calling` (Agent Skill, multi-file: 2 files) - Install (CLI): `npx skillmds@latest add diegosouzapw/hic-tad-calling` - Raw SKILL.md: https://api.skillmd.com/api/skills/diegosouzapw/hic-tad-calling/raw - Safety review: pending (external: skill-scanner PASS, skillspector PASS) - Works with: Claude Code, Claude.ai, OpenAI Codex - Category: Coding & Dev Tools - Author: diegosouzapw (https://skillmd.com/u/diegosouzapw) - Updated: 2026-09-08 - Page: https://skillmd.com/skills/diegosouzapw/hic-tad-calling --- # 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. --- ## 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. --- ## 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 ```bash ${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/ ${sample}_track.ini # Configuration file for visualization ``` --- ## Allowed Tools When using this skill, you should restrict yourself to the following MCP tools from server `cooler-tools`, `cooltools-tools`, `project-init-tools`, `genome-locate-tools`: - `mcp__project-init-tools__project_init` - `mcp__genome-locate-tools__genome_locate_fasta` - `mcp__HiCExplorer-tools__hic_to_mcool` - `mcp__HiCExplorer-tools__check_mcool_file` - `mcp__HiCExplorer-tools__run_hicFindTADs` - `mcp__HiCExplorer-tools__generate_track_ini` - `mcp__HiCExplorer-tools__plot_tads_region` Do NOT fall back to: - raw shell commands (`hicFindTADs`, `hicPlotTADs`, etc.) - ad-hoc Python snippets (e.g. importing `cooler`, `bioframe`, `matplotlib` manually in the reply). --- ## Decision Tree ### Step 0 — Gather Required Information from the User Before calling any tool, ask the user: 1. Sample name (`sample`): used as prefix and for the output directory `${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 `${mcool_uri}` --- ### Step 1: Initialize Project 1. Make director for this project: Call: - `mcp__project-init-tools__project_init` with: - `sample`: the user-provided sample name - `task`: TAD_calling The tool will: - Create `${sample}_TAD_calling` directory. - Get the full path of the `${sample}_TAD_calling` directory, which will be used as `${proj_dir}`. --- 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. --- 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}`. --- ### 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 `${proj_dir}/TADs/` directory. --- ## Step 3: Visualization 1. generate the `` file first for visualization Call: - `mcp__HiCExplorer-tools__generate_track_ini` with: - `sample`: `${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 `` file under `${proj_dir}/temp/` directory. - Return the path of the `` file. --- 2. Contact Maps with TAD Overlays Before calling the tool, **ask the user** for the target region, like `"chr22:1000000-2000000"`. Call: - `mcp__HiCExplorer-tools__plot_tads_region` with: - `sample`: `${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. --- # 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.