Individual skill
tooluniverse-regulatory-genomics
Transcription factor binding, cis-regulatory elements (cCREs), chromatin accessibility, and regulatory annotation using JASPAR (motifs), UniBind, ENCODE (cCREs, ChIP-seq), RegulomeDB (regulatory variant scoring), UCSC, and the Ensembl Regulatory Build (motif instances, evolutionarily constrained elements, TF binding matrices) — plus sequence-based deep-learning prediction of regulatory activity and non-coding variant effects (AlphaGenome, Enformer, Borzoi, ChromBPNet, Evo 2). Use for regulatory element annotation, TF-binding-site prediction, regulatory-region functional impact assessment, and predicting how a non-coding variant or a raw DNA sequence affects expression/chromatin/accessibility. Use this whenever a user asks what regulates a gene, whether a SNP hits a regulatory element, or to predict a non-coding variant's functional effect from sequence.
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# Regulatory Genomics Research Skill
Systematic investigation of gene regulation through transcription factor binding, chromatin state, and regulatory element annotation. Integrates JASPAR (TF motifs), ENCODE (functional genomics experiments), RegulomeDB (regulatory variant scoring), and UCSC cCREs.
## Domain Reasoning
Regulatory element identification requires converging lines of evidence: sequence conservation alone is insufficient (many conserved sequences are not regulatory), chromatin accessibility is necessary but not sufficient (open chromatin can be structural), TF binding peaks require motif validation, and eQTL evidence ties the element to a transcriptional outcome. No single data type is sufficient. A high-confidence regulatory element requires at least two independent evidence types, and ideally all four.
## LOOK UP DON'T GUESS
- TF binding motifs: retrieve from `jaspar_search_matrices` and `jaspar_get_matrix`; do not describe motifs from memory.
- Experimental ChIP-seq data: search `ENCODE_search_experiments`; do not assume a TF has been profiled in a given cell type.
- cCRE annotations for a genomic region: call `UCSC_get_encode_cCREs` with exact coordinates; do not guess element types.
- Regulatory impact of a variant: query `RegulomeDB_query_variant`; never estimate regulatory importance from position alone.