Gene Regulatory Network Analysis

Gene Regulatory Network Analysis

GRN inference starts with: which TF regulates which gene? Direct evidence (ChIP-seq binding) is stronger than indirect (co-expression correlation). A TF binding near a gene doesn't prove regulation — check if expression changes when the TF is perturbed. JASPAR provides binding motifs but motif presence in a promoter is only computational evidence (T3); ENCODE ChIP-seq data that places the TF at the locus in the relevant cell type is stronger (T1). eQTLs from GTEx show which variants affect expression but don't identify the upstream regulator — combine with TF motif disruption analysis for mechanistic insight.

LOOK UP DON'T GUESS: never assume JASPAR matrix IDs, Enrichr library names, or GTEx tissue identifiers — always search JASPAR by TF name and verify library names before calling enrichr.

When to Use

Activate this skill when the user asks about:

• Transcription factor (TF) binding sites, motifs, or target genes
• Gene regulatory networks or transcriptional regulation
• Chromatin state and histone modifications in regulatory context
• TF-target relationships and co-regulation
• eQTL effects on gene regulation
• Protein-protein interactions among regulatory factors

COMPUTE, DON'T DESCRIBE

When analysis requires computation (statistics, data processing, scoring, enrichment), write and run Python code via Bash. Don't describe what you would do — execute it and report actual results. Use ToolUniverse tools to retrieve data, then Python (pandas, scipy, statsmodels, matplotlib) to analyze it.

Workflow

Phase 0: Input Disambiguation

Determine:

• Is the query about a specific TF (e.g., "TP53 regulatory network") or a target gene (e.g., "what regulates CDKN1A")?
• Is a specific tissue/cell type relevant?
• Should the analysis focus on direct binding (motifs) or functional targets (ChIP-seq, enrichment)?

Phase 1: TF Motif Lookup (JASPAR)

Search JASPAR for the TF's position weight matrix (PWM) and binding motif profile.

Tool: jaspar_search_matrices

Parameters:
  search   string   TF name to search (e.g., "TP53")
  limit    integer  Max results (default 10)
  collection string JASPAR collection filter (e.g., "CORE")
  species  string   Taxonomy ID filter (e.g., "9606" for human)