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Comprehensive guide for visualizing ENCODE data including deeptools heatmaps, IGV screenshots, UCSC track hubs, and publication-quality plots. Use when users need to create visualizations of ChIP-seq signal, peak landscapes, genome browser views, or any visual representation of ENCODE data. Trigger on: heatmap, visualization, genome browser, track hub, IGV, deeptools, signal plot, peak visualization, profile plot, publication figure, bigWig visualization.

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Generate proper ENCODE citations for publications, grants, and presentations. Use when the user needs to cite ENCODE data, create bibliography entries, write acknowledgment sections, or ensure compliance with ENCODE data use policy.

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Convert genomic coordinates between assembly versions (GRCh37/hg19 to GRCh38/hg38, mm9 to mm10). Guides UCSC liftOver for BED files, CrossMap for VCF/bigWig, and handles unmapped regions with provenance logging.

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Access ENCODE uniform analysis pipelines, generate user-specific Nextflow/WDL pipelines, manage compute resources, and integrate with cloud platforms. Use when the user wants to understand ENCODE pipelines, run pipelines on their own data, generate custom Nextflow workflows from ENCODE pipeline code, check compute requirements (CPU/GPU/memory), run pipelines in background, or integrate with Google Cloud, AWS, or other cloud platforms. Also use when the user asks about ENCODE pipeline outputs, processing standards, software versions, or wants to replicate ENCODE processing. Covers local execution, HPC, and cloud deployment with resource-aware scheduling. Use this skill for ANY pipeline execution, workflow generation, or compute resource management task involving ENCODE data.

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Execute ENCODE ChIP-seq processing pipeline from FASTQ to peaks and signal tracks. Child of pipeline-guide. Provides stage-by-stage Nextflow execution with Docker containers and cloud deployment. Use when users need to process ChIP-seq data following ENCODE standards, run peak calling with MACS2, perform IDR analysis, or generate signal tracks. Trigger on: ChIP-seq pipeline, run ChIP-seq, process ChIP-seq, MACS2 peak calling, IDR analysis, ChIP-seq FASTQ processing.

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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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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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Guide for multi-experiment batch operations: QC screening, batch download, comparison, and report generation across many ENCODE experiments simultaneously. Use when users need to process 5+ experiments together, create experiment comparison tables, perform batch quality checks, or generate summary reports. Trigger on: batch analysis, multiple experiments, bulk processing, experiment comparison, batch QC, multi-sample, batch download, experiment table, summary report, collection analysis.

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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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Query the Ensembl REST API for regulatory feature annotations, variant effect prediction (VEP), coordinate liftover, gene lookups, and cross-references. Use when the user needs to annotate variants with VEP (consequence, CADD, REVEL, SpliceAI), check Ensembl Regulatory Build overlap for ENCODE regions, convert coordinates between GRCh37 and GRCh38, resolve gene IDs (Ensembl ↔ symbol ↔ RefSeq), look up gene phenotype associations, or cross-reference ENCODE targets with Ensembl annotations. Also use when the user mentions Ensembl, VEP, variant effect predictor, liftover, assembly conversion, regulatory build, gene lookup, or cross-references between databases.

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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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Query gnomAD (Genome Aggregation Database) for population allele frequencies, gene constraint scores, and variant annotations to interpret ENCODE regulatory variants. Use when the user needs allele frequencies for variants in ENCODE regulatory elements, wants to assess gene constraint (pLI, LOEUF) for ENCODE target genes, needs population-specific frequencies for GWAS variants overlapping cCREs, wants to filter variants by rarity before functional annotation, or is interpreting ENCODE CRISPR/MPRA results in the context of population genetics. Also use when the user mentions gnomAD, allele frequency, pLI, LOEUF, constraint, rare variants, population frequency, ExAC, or variant 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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Build comprehensive chromatin contact maps by aggregating Hi-C loop calls (BEDPE) across multiple ENCODE experiments, donors, and labs. Use when the user wants to answer "what regions are in 3D contact in my tissue?" by creating a union catalog of chromatin loops. Handles resolution-aware anchor matching, cross-lab variation, and Hi-C-specific quality metrics.

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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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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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Guide for annotating ENCODE peaks with genomic features using ChIPseeker and GREAT. Use when users need to assign peaks to genes, determine genomic feature distribution (promoter, intron, intergenic), or perform gene ontology enrichment of peak-associated genes. Trigger on: peak annotation, ChIPseeker, GREAT, peak to gene, genomic feature, promoter enrichment, gene ontology, peak distribution, TSS distance, nearest gene.

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Execute ENCODE ATAC-seq processing pipeline from FASTQ to peaks and signal tracks. Child of pipeline-guide. Provides stage-by-stage Nextflow execution with Docker containers and cloud deployment. Handles Tn5 transposase offset correction, mitochondrial read removal, and nucleosome-free fragment selection. Use when users need to process ATAC-seq data following ENCODE standards. Trigger on: ATAC-seq pipeline, run ATAC-seq, process ATAC-seq, chromatin accessibility, open chromatin, Tn5 shift, TSS enrichment.

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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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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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Execute CUT&RUN processing pipeline from FASTQ to peaks and signal tracks. Child of pipeline-guide. Provides Nextflow execution with Docker and cloud deployment. Use when processing CUT&RUN or CUT&Tag data, an alternative to ChIP-seq with lower background. Trigger on: CUT&RUN pipeline, CUT&Tag, SEACR, Henikoff, targeted chromatin, pA-MNase, process CUT&RUN.

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Execute ENCODE RNA-seq pipeline from FASTQ to gene quantification and signal tracks. Child of pipeline-guide. Provides Nextflow execution with Docker and cloud deployment. Use when processing RNA-seq data with STAR alignment, RSEM/Kallisto quantification, or generating expression matrices. Trigger on: RNA-seq pipeline, gene expression, STAR alignment, RSEM quantification, transcript quantification, TPM, FPKM, RNA processing, run RNA-seq.

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Execute ENCODE Whole Genome Bisulfite Sequencing (WGBS) pipeline from FASTQ to methylation calls. Child of pipeline-guide. Provides Nextflow execution with Docker and cloud deployment. Use when processing WGBS/bisulfite-seq data, calling methylation levels, generating bedMethyl files. Trigger on: WGBS pipeline, bisulfite sequencing, methylation calling, DNA methylation pipeline, bismark, bwa-meth, bedMethyl.

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Search and explore ENCODE Project genomics data. Use when the user wants to find experiments, files, or explore what data is available for specific assays, organs, cell lines, or targets.

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