Claude-skill-registry nested-TAD-detection

This skill detects hierarchical (nested) TAD structures from Hi-C contact maps (in .cool or mcool format) using OnTAD, starting from multi-resolution .mcool files. It extracts a user-specified chromosome and resolution, converts the data to a dense matrix, runs OnTAD, and organizes TAD calls and logs for downstream 3D genome analysis.

install

source · Clone the upstream repo

git clone https://github.com/majiayu000/claude-skill-registry

Claude Code · Install into ~/.claude/skills/

T=$(mktemp -d) && git clone --depth=1 https://github.com/majiayu000/claude-skill-registry "$T" && mkdir -p ~/.claude/skills && cp -r "$T/skills/data/31-toolbased-nested-tad-detection" ~/.claude/skills/majiayu000-claude-skill-registry-nested-tad-detection && rm -rf "$T"

manifest: skills/data/31-toolbased-nested-tad-detection/SKILL.md

Nested TAD Detection from .mcool Using OnTAD

Overview

This skill performs nested TAD (hierarchical TAD/subTAD) detection from Hi-C data using OnTAD, starting from a .mcool, .cool or .hic file.

Main steps include:

Refer to the Inputs & Outputs section to verify required files and output structure.
Inspect the
```
.mcool
```
file to list available resolutions and alway remember to confirm the chromosome name and analysis resolution with the user.
Extract a balanced or raw dense Hi-C matrix for a selected chromosome and resolution from the
```
.mcool
```
file.
Ensure matrix quality (symmetry, no all-zero rows/columns, reasonable contact decay).
Run OnTAD to call TADs and nested TAD structures.
Parse and standardize OnTAD output into BED-like tables and hierarchical annotation files.

When to use this skill

Use this skill when you want to identify TADs and nested sub-TADs from high- or mid-resolution Hi-C data, especially when your contact maps are stored as Cooler multi-resolution files (.mcool) and you need chromosome- and resolution-specific OnTAD calls.

Typical biological questions / use-cases:

Comparing TAD hierarchy between cell types (e.g., GM12878 vs K562) or conditions (control vs treated).
Investigating whether inner subTADs are enriched for active regulatory elements, specific histone marks, or gene expression.
Studying boundary usage, boundary sharing, or hierarchical TAD levels around key loci (e.g., HOX clusters, oncogenes).
Integrating nested TAD structure with ChIP-seq, ATAC-seq, or WGBS to understand spatial regulatory architecture.

Data quality & replication assumptions:

Hi-C experiments should have sufficient depth for the target resolution (e.g., ≥5–10 kb typically requires deep sequencing).
Preferably, use biological replicates per condition and call TADs on either:
- individual replicate matrices (and then merge/consensus), or
- replicate-merged matrices (if justified).
The
```
.mcool
```
should be properly normalized or at least QC’d (ICE/balanced weights available if using
```
--balanced
```
).

Inputs & Outputs

Inputs

Required core inputs:

Hi-C matrix file
- Multi-resolution Cooler file (
```
.mcool
```
  ), e.g.:
  - ```
  sample.mcool
```
- Or one-resolution Cooler file (
```
.cool
```
  ), e.g.:
  - ```
  sample.cool
```
- Or Hi-C file (
```
.hic
```
  ), e.g.:
  - ```
  sample.hic
```
User-supplied parameters (must come from user feedback)
- Chromosome name: e.g.,
```
chr1
```
  ,
```
chr2
```
  ,
```
chrX
```
- Resolution of interest: e.g.,
```
10000
```
  ,
```
25000
```
  ,
```
40000
```
  (in bp)
- Chromosome length: e.g., 133275309
Software and environment
- ```
cooler
```
  command-line utilities (or Python
```
cooler
```
  module) available in
```
$PATH
```
  or environment.
- ```
OnTAD
```
  installed and callable (e.g.,
```
OnTAD
```
  or
```
OnTAD_linux
```
  command).
- ```
python
```
  (3.x) and basic scientific Python stack if using Python-based extraction.

Optional entry point:

Precomputed dense Hi-C matrix (OnTAD-ready)
- Plain text dense square matrix (no header), e.g.
```
proj_dir/matrices/chr17_25kb_dense.matrix
```
  .
- If this is already present, you may skip the
  .mcool
  → dense matrix conversion and jump directly to OnTAD.

Operational rules for missing inputs:

.mcool

.cool

.hic

file is missing:

"sample.mcool not available, provide required files or skip and proceed ?"

If chromosome list not specified:
Ask the user explicitly rather than assuming default.
If OnTAD executable is not found:
Ask user to install/locate OnTAD before proceeding.

Outputs

Default output directory structure:

${sample}_nested_TAD_detection/
    matrices/
        ${chromosome}_${resolution}_dense.txt
        ${chromosome}_${resolution}_dense.log
    nested_TADs/
        ${chromosome}_${resolution}_OnTAD.tad
        ${chromosome}_${resolution}_OnTAD.bed
        ${chromosome}_${resolution}_OnTAD.log

Allowed Tools

When using this skill, you should restrict yourself to the following MCP tools from server

cooler-tools

cooltools-tools

plot-hic-tools

project-init-tools

```
mcp__project-init-tools__project_init
```

mcp__cooler-tools__list_mcool_resolutions

mcp__cooler-tools__harmonize_chrom_names

```
mcp__cooler-tools__dump_chroms
```
```
mcp__cooler-tools__dump_dense_matrix
```
```
mcp__OnTAD-tools__run_ontad
```

Do NOT fall back to:

raw shell commands (
```
OnTAD
```
, 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:

Sample name (
```
sample
```
): used as prefix and for the output directory
```
${sample}_nested_TAD_detection
```
.
Genome assembly (
```
genome
```
): e.g.
```
hg38
```
,
```
mm10
```
,
```
danRer11
```
.
- Never guess or auto-detect.
Hi-C matrix path/URI (
```
mcool_uri
```
):
- ```
path/to/sample.mcool::/resolutions/25000
```
  (.mcool file with resolution specified)
- or
```
.cool
```
  file path
- or
```
.hic
```
  file path
Resolution (
```
resolution
```
): default
```
25000
```
(100 kb).
- If user does not specify, use
```
25000
```
  as default.
- Must be the same as the resolution used for
```
${mcool_uri}
```

Step 1 — Initialize Project

Make director for this project:

Call:

```
mcp__project-init-tools__project_init
```

with:

```
sample
```
: the user-provided sample name
```
task
```
: hic_matrix_qc

The tool will:

Create
```
${sample}_nested_TAD_detection
```
directory.
Return the full path of the
```
${sample}_nested_TAD_detection
```
directory, which will be used as
```
${proj_dir}
```
.

If the user provides a
```
.hic
```
file, convert it to
```
.mcool
```
file 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}_nested_TAD_detection
```
directory returned by
```
mcp__project-init-tools__project_init
```
.

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.

Step 2: List Available Resolutions in the .mcool file & Modify the Chromosome Names if Necessary

Check the resolutions in
```
mcool_uri
```
:

Call:

mcp__cooler-tools__list_mcool_resolutions

with:

```
mcool_path
```
: the user-provided path (e.g.
```
input.mcool
```
) without resolution specified.

The tool will:

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

If the user defined or default

${resolution}

is not found in the list, ask the user to specify the resolution again. Else, use

${resolution}

for the following steps.

Check if the chromosome names in the .mcool file are started with "chr", and if not, modify them to start with "chr":

Call:

mcp__cooler-tools__harmonize_chrom_names

with:

```
sample
```
: the user-provided sample name
```
proj_dir
```
: directory to save the expected-cis and eigs-cis files. In this skill, it is the full path of the
```
${sample}_Compartments_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

The tool will:

Check if the chromosome names in the .mcool file.
If not, harmonize the chromosome names in the .mcool file.
If the chromosome names are modified, return the path of the modified .mcool file under
```
${proj_dir}/
```
directory

Step 3: Check chromosome length

Call:

```
mcp__cooler-tools__dump_chroms
```

with:

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

The tool will:

Return the chromosome name and length as a table.

Step 4: Extract dense matrix from

.mcool

Call:

```
mcp__cooler-tools__dump_dense_matrix
```

with:

```
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}_nested_TAD_detection
```
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
```
chrom
```
: the user-provided chromosome name (e.g.
```
chr17
```
)
```
balanced
```
: whether to use balanced matrix (default: True)

The tool will:

Extract the dense matrix from the .mcool file.
Return the path of the dense matrix file.

Step 5: Run OnTAD

Call:

```
mcp__OnTAD-tools__run_ontad
```

with:

```
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}_nested_TAD_detection
```
directory returned by
```
mcp__project-init-tools__project_init
```
.

dense_matrix

: the path to the dense matrix file (e.g.

${proj_dir}/matrices/chr17_25kb_dense.matrix

)

```
chrom
```
: the user-provided chromosome name (e.g.
```
chr17
```
)
```
chrom_length
```
: the corresponding chromosome length (e.g. 83257441) returned by
```
mcp__cooler-tools__dump_chroms
```
tool.
```
resolution
```
: the user-provided resolution (e.g. 25000)
```
penalty
```
: the penalty parameter for OnTAD (e.g. 0.1)
```
maxsz
```
: the maximum TAD size (in bins) (e.g. 200)

The tool will:

Run OnTAD to call TADs and nested TAD structures.
Return the path of the OnTAD output file (.tad, .bed, .log).