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Query the UCSC Genome Browser REST API to retrieve regulatory tracks, DNA sequences, cCRE annotations, TF binding clusters, and track schemas for any genomic region. Use when the user wants to look up what regulatory elements exist at a genomic locus, retrieve DNA sequence under peaks, query ENCODE cCREs or TF rPeak clusters from UCSC, check what tracks are available for a genome assembly, get chromatin accessibility across cell types, or cross-reference ENCODE data with UCSC-hosted annotations. Also use when the user mentions UCSC, genome browser, cCRE lookup, SCREEN, TF binding clusters, DNA sequence retrieval, or track data extraction.

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Conduct rigorous cross-study meta-analysis of scRNA-seq data from ENCODE, integrating multiple single-cell transcriptomic datasets for a tissue/cell type. Use when the user wants to answer "what cell types exist in my tissue and what genes define them?" by combining scRNA-seq data across donors, labs, and platforms. Follows the Mawla et al. 2019 framework for assessing cross-study reproducibility, TIN-based quality filtering, and detection-limit-aware interpretation. Handles batch correction (Harmony/Seurat), dropout awareness, cross-contamination artifacts, and platform-specific biases. Use this skill for ANY scRNA-seq integration task, cross-dataset comparison, cell atlas construction, or reproducibility assessment involving ENCODE single-cell data.

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Generate publication-ready methods sections, figure legends, supplementary tables, and data availability statements from ENCODE analysis provenance. Implements the scientific documentation standards requiring complete metadata reporting. Use when the user needs to write methods, generate figure legends, create supplementary tables, draft data availability statements, compile tool citations, or auto-generate any publication text from their ENCODE analysis. Trigger on: methods section, figure legend, supplementary table, data availability, tool citations, publication writing, manuscript, write methods, methods draft, write up, write-up, paper writing, reproducible methods.

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Discover and characterize regulatory elements (enhancers, promoters, silencers, insulators, super-enhancers) using ENCODE data and the cCRE catalog. Use when the user wants to find candidate regulatory elements, identify active enhancers in a tissue, map promoter states, classify chromatin states with ChromHMM, identify super-enhancers with ROSE, understand the functional validation hierarchy (CRISPR > MPRA > reporter), or characterize non-coding genomic regions. Covers the full workflow from ENCODE cCRE lookup through chromatin state segmentation to functional validation and enhancer-gene linkage. Use this skill for ANY regulatory element discovery, classification, or characterization task.

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Build comprehensive DNA methylation maps by aggregating WGBS (Whole Genome Bisulfite Sequencing) data across multiple ENCODE experiments, donors, and labs. Use when the user wants to answer "where is DNA methylated/unmethylated in my tissue?" by combining per-CpG methylation data into tissue-level methylation profiles. Handles coverage filtering, identifies hypomethylated regions (HMRs) and partially methylated domains (PMDs), and manages cross-lab variation.

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Guide for using JASPAR transcription factor binding profiles with ENCODE ChIP-seq data. Use when users need to find TF binding motifs in ENCODE peaks, validate ChIP-seq targets with known motifs, or scan regulatory regions for TF binding potential. Trigger on: JASPAR, motif database, binding profile, PWM, position weight matrix, TF motif, motif enrichment, motif scanning, binding site prediction.

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Plan and execute integrative analysis combining multiple ENCODE experiments for cross-dataset or multi-omic workflows. Use when the user wants to combine experiments, perform cross-dataset comparison, multi-omic integration, peak overlap analysis, differential binding, signal correlation, chromatin state segmentation, enhancer-gene linkage, or any analysis that requires merging or comparing data from two or more ENCODE experiments. Covers same-assay cross-sample, multi-omic same-sample, cross-organism, and perturbation integration designs. Guides compatibility checks, batch effect detection, normalization, integration strategy selection, and provenance documentation.

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Build comprehensive histone mark maps by aggregating narrowPeak data across multiple ENCODE experiments, donors, and labs. Use when the user wants to answer "where is this histone mark present in my tissue?" by combining peak calls from multiple studies into a union peak set with confidence annotations. Handles cross-lab batch effects, broad vs narrow marks, and ENCODE blocklist filtering.

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Guide for integrating NHGRI-EBI GWAS Catalog associations with ENCODE regulatory data. Use when users need to find GWAS variants in ENCODE peaks, connect regulatory elements to disease associations, or prioritize functional variants using ENCODE annotations. Trigger on: GWAS, genome-wide association, SNP association, trait association, GWAS Catalog, disease association, risk variant, lead SNP, LD proxy.

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Guide for integrating GTEx tissue expression data with ENCODE regulatory elements. Use when users need to check if a gene is expressed in a tissue, correlate regulatory elements with expression, or validate ENCODE findings against GTEx. Trigger on: GTEx, tissue expression, gene expression levels, expression atlas, eQTL, tissue-specific expression, TPM values.

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Search, query, and cross-reference NCBI GEO (Gene Expression Omnibus) datasets with ENCODE experiments. Use when the user wants to find GEO accessions for ENCODE experiments, search GEO for complementary datasets, download GEO metadata or series matrices, cross-reference ENCODE and GEO data, find supplementary files from GEO, or link GEO series to ENCODE experiments for provenance tracking. Also use when the user mentions GEO, GSE, GSM, GPL, GDS, series matrix, SOFT format, or needs to find expression data in GEO that complements their ENCODE analysis.

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Analyze ENCODE functional genomics screens including CRISPR screens, MPRA (Massively Parallel Reporter Assays), and STARR-seq. Find screen data in ENCODE, process results, identify functional elements, and integrate with epigenomic annotations.

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Build comprehensive epigenomic profiles for tissues or cell types using ENCODE data. Use when the user wants to characterize chromatin states, assemble histone modification panels, create epigenomic landscapes, run ChromHMM segmentation, identify super-enhancers or bivalent domains, profile regulatory elements across a biosample, or understand epigenetic regulation in a specific biological context. Covers histone marks, chromatin accessibility, TF binding, transcription, DNA methylation, and 3D genome structure.

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Cross-reference ENCODE data with PubMed, bioRxiv, ClinicalTrials.gov, Open Targets, GTEx, ClinVar, GWAS Catalog, gnomAD, Ensembl, and other scientific databases. Use when the user wants to find publications, preprints, or clinical trials related to ENCODE experiments, chain ENCODE data with other scientific MCP servers, or build translational pipelines from genomic data to clinical application.

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Track exact provenance for every operation on ENCODE data — tool versions, reference files, scripts, parameters, and timestamps — to enable publication-ready methods writing. Use when the user processes ENCODE files, runs any bioinformatics tool, creates filtered/merged datasets, runs pipelines, performs liftover, uses R/Python/Bash for analysis, or needs to document their analysis chain for reproducibility and publication. Also use when the user says "write me methods" to auto-generate methods sections from the provenance log. This skill implements comprehensive provenance documentation: every tool, every version, every reference file, every parameter, every accession — no shortcuts. Use this skill for ANY processing step, ANY file transformation, ANY analysis operation on ENCODE data.

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Guide for integrating CellxGene Census single-cell data with ENCODE bulk experiments. Use when users need cell-type-specific expression context for ENCODE regulatory data, want to deconvolve bulk ENCODE signals, or validate regulatory elements at single-cell resolution. Trigger on: CellxGene, single-cell atlas, cell type expression, Census, cell type specificity, single-cell context, scRNA-seq atlas.

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Compare ENCODE experiments across different biosamples, tissues, or cell lines to identify tissue-specific regulatory patterns. Use when the user wants cross-tissue comparison, cell-type comparison, tissue-specific elements, differential chromatin, biosample matching, disease vs normal comparison, developmental time course, constitutive vs variable regulation, or multi-tissue data availability mapping. Handles batch effect detection, biosample hierarchy, and comparison design.

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Build comprehensive chromatin accessibility maps by aggregating ATAC-seq and DNase-seq narrowPeak data across multiple ENCODE experiments, donors, and labs. Use when the user wants to answer "where is chromatin accessible in my tissue?" by combining peak calls into a union peak set. Handles cross-lab variation, ATAC vs DNase platform differences, and ENCODE blocklist filtering.

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Track ENCODE experiments locally with publications, citations, and provenance. Use when the user wants to build a collection of experiments, manage citations, compare experiments, or track data provenance.

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Integrate multiple ENCODE data types (RNA-seq, ATAC-seq, Histone ChIP-seq, TF ChIP-seq) for a tissue/cell type to build a comprehensive regulatory landscape. Use when the user wants to answer "what are the enhancers, promoters, and regulatory elements active in my tissue, and which transcription factors control them?" by layering expression, chromatin accessibility, histone marks, and TF binding data. Follows the Mawla et al. 2023 framework for cross-assay integration of islet cell type-specific data. Handles chromatin state annotation (ChromHMM), enhancer-gene linkage, TF motif enrichment, and cell type-specific regulatory element identification. Use for ANY multi-omic analysis, enhancer discovery, regulatory network construction, or epigenomic characterization using ENCODE data.

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Analyze system architecture, module structure, API contracts, data models, and code patterns. Use when designing systems, reviewing module boundaries, evaluating API designs, analyzing data models, checking pattern conformance, tracing decisions, or reviewing frontend architecture. Triggers: "architecture", "module design", "API design", "data model", "boundaries", "patterns", "decisions", "frontend architecture".

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Spring Boot 4 data layer implementation for Domain-Driven Design. Use when implementing JPA or JDBC aggregates, Spring Data repositories, transactional services, projections, or entity auditing. Covers aggregate roots with AbstractAggregateRoot, value object mapping, EntityGraph for N+1 prevention, and Spring Boot 4 specifics (JSpecify null-safety, AOT repositories). For DDD concepts and design decisions, see the domain-driven-design skill.

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Rapid UI prototyping — generates 3 visually distinct HTML/CSS components from a text prompt and serves them in a live browser gallery. Use when user runs /prototype, asks to "prototype a UI", "mock up a component", "generate HTML mockups", "create UI variations", "design exploration", "quick UI concept", or wants to see multiple visual approaches to a component. Also trigger when user says "show me different ways to build...", "explore different designs for...", or wants rapid visual exploration of a UI idea — even without saying "prototype" explicitly.

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Transform vague inputs into precision-optimized AI prompts for Claude, ChatGPT, Gemini, or other LLMs. Use when user mentions "optimize prompt", "improve prompt", "lyra", "prompt engineering", or needs help crafting effective AI prompts.

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