tooluniverse-gene-regulatory-networks

Analyze gene regulatory networks using TF motifs, ChIP-seq, eQTL, and interaction databases.

1.7k|254|Updated Mar 3, 2025
One-click install
npx skills add https://github.com/mims-harvard/ToolUniverse --skill tooluniverse-gene-regulatory-networks
Or copy as Structured Prompt for Agent▼
Please help me install this Agent Skill.
Skill: tooluniverse-gene-regulatory-networks
Source: https://github.com/mims-harvard/ToolUniverse/tree/main/plugins/tooluniverse/skills/tooluniverse-gene-regulatory-networks
Command: npx skills add https://github.com/mims-harvard/ToolUniverse --skill tooluniverse-gene-regulatory-networks

SYSTEM DOCUMENTATION & REQUIREMENTS

What problem does it solve?

Determining which transcription factors regulate a gene, or which genes a TF targets, requires querying many scattered databases (JASPAR, ENCODE, GTEx, STRING, Enrichr) and distinguishing direct binding evidence from indirect co-expression. This Skill orchestrates those lookups into a coherent regulatory network analysis workflow with graded evidence.

Core Features & Use Cases

  • TF-Target Inference: Search JASPAR for binding motifs, query Enrichr libraries (ENCODE ChIP-seq, ChEA, TRRUST) for TF-target relationships, and integrate GTEx eQTL data.
  • Regulatory Context: Retrieve ENCODE histone modification experiments, RegulomeDB variant scores, and protein interaction networks from STRING, IntAct, and BioGRID.
  • Evidence Grading: Classify findings into tiers (T1 ChIP-seq/eQTL through T4 literature mentions) to separate direct binding evidence from computational predictions.
  • Use Case: Ask "which TFs regulate CDKN1A?" and receive an analysis combining ChIP-seq enrichment, eQTL data, chromatin context, and literature support.

Quick Start

Ask which transcription factors regulate the gene CDKN1A and request a regulatory network with supporting evidence tiers.

Frequently Asked Questions about tooluniverse-gene-regulatory-networks

High-intent search queries and answers about installing and using this skill.

FAQPage Schema
How do I find which transcription factors regulate a gene?▼

Run Enrichr enrichment with the ENCODE_TF_ChIP-seq_2015 or ChEA_2022 library on the gene's co-regulated set to identify binding TFs. Complement this with GTEx eQTL queries and ENCODE histone experiments for regulatory context at the locus.

How do I find target genes of a transcription factor like TP53?▼

Search JASPAR for the TF's binding motif with jaspar_search_matrices, then use the TRRUST_Transcription_Factors_2019 Enrichr library for curated targets. STRING interaction partners and literature searches add further evidence.

What is the difference between direct and indirect regulatory evidence?▼

Direct evidence (T1) comes from ChIP-seq showing physical TF binding at a locus or validated JASPAR motifs. Indirect evidence (T3) includes co-expression correlation and statistical enrichment, which suggest but do not prove regulation.

Does JASPAR motif presence prove a TF regulates a gene?▼

No. A motif match in a promoter is only computational evidence (T3). Confirm regulation with ENCODE ChIP-seq data placing the TF at the locus in the relevant cell type, or perturbation experiments showing expression changes.

Why does my Enrichr query fail for regulatory analysis?▼

Enrichr requires gene_list as a JSON array of gene symbols, not a single string, and library names must match exactly (e.g., ENCODE_TF_ChIP-seq_2015). Verify library names before calling rather than guessing them.

Can I analyze tissue-specific gene regulation with GTEx?▼

Yes. GTEx_query_eqtl returns tissue-specific eQTLs for a gene symbol, showing where variants affect expression. Combine with tissue-filtered ENCODE histone experiments and RegulomeDB scores for tissue-specific regulatory annotation.