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.