Dr. Alex M. Mawla, PhD

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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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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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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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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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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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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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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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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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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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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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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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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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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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 DNase-seq pipeline from FASTQ to hotspots and footprints. Child of pipeline-guide. Provides Nextflow execution with Docker and cloud deployment. Use when processing DNase-seq data, calling DNase hypersensitive sites, performing footprinting analysis. Trigger on: DNase-seq pipeline, DNase hypersensitive, DHS, Hotspot2, footprinting, DNase I, chromatin accessibility DNase.

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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 Hi-C pipeline from FASTQ to contact matrices and loop calls. Child of pipeline-guide. Provides Nextflow execution with Docker and cloud deployment. Use when processing Hi-C data, generating contact matrices, or calling loops. Trigger on: Hi-C pipeline, chromatin conformation, contact matrix, loop calling, TAD detection, Juicer, HiCCUPS, 3D genome.

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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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Evaluate ENCODE experiment quality using standard metrics and audit flags. Use when the user asks about data quality, wants to filter for high-quality experiments, needs to interpret quality metrics (FRiP, NSC, RSC, NRF, IDR, TSS enrichment, fragment size), wants to understand ENCODE audit warnings, needs to compare quality across experiments, or is deciding whether data is usable for their analysis. Also use when the user mentions QC, quality control, or data filtering.

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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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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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