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Tests whether two genomic interval sets overlap (colocalize) more than expected by chance using a permutation test against a structured-genome null model. Covers bedtools fisher (analytic 2x2 screen), bedtools shuffle + jaccard permutation, GAT (isochore/GC-conditioned simulation with FDR), regioneR (flexible permutation, randomizeRegions vs circularRandomizeRegions, localZScore), LOLA (universe-relative Fisher against a region database), and GREAT/rGREAT (regulatory-domain binomial + hypergeometric for ontology-from-regions). Stresses the universe/background choice, matched background, blacklist exclusion, and multiple-testing control. Use when asking whether peaks/regions are enriched at enhancers/TFBS/features, scoring region-set colocalization or region-set enrichment, comparing CNV/SV concordance, or turning an overlap count into a defensible p-value.

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Generates, normalizes, and converts bedGraph signal tracks (4-column chrom/start/end/value, 0-based half-open) with bedtools genomecov, deepTools bamCoverage/bamCompare/bigwigCompare, bedtools unionbedg, and UCSC bedGraphToBigWig. Covers why a raw coverage bedGraph is not comparable across samples until normalized, the CPM/RPKM/BPM/RPGC normalization menu and the conserved-total assumption that makes them wrong under a global perturbation, the strict sorted-non-overlapping-chrom.sizes bedGraphToBigWig contract that silently corrupts a bigWig, effective-genome-size selection, and bin-size aliasing. Use when building or normalizing a coverage/signal track from a BAM, comparing tracks across samples or conditions, converting bedGraph to a browser-ready bigWig, or diagnosing a track that looks plausible but reports wrong heights.

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Reads, queries, and writes bigWig indexed binary signal tracks (coverage, fold-change, conservation, methylation-rate) with pyBigWig (Python) and the UCSC Kent tools (bedGraphToBigWig, bigWigToBedGraph, bigWigInfo, bigWigSummary, bigWigAverageOverBed) and deepTools (multiBigwigSummary, computeMatrix, bigwigCompare). Covers the central trap that a wide query returns a precomputed zoom-level summary (by default the mean, which annihilates narrow peaks) not per-base data, when exact=True/values() is mandatory, the NaN-not-zero gap-handling fork, choosing mean vs max vs sum vs coverage by biological question, and the sorted-bedGraph plus chrom.sizes build requirement. Use when extracting signal at regions, computing mean signal per gene/peak, building a browser track from bedGraph, comparing tracks, or building TSS/gene-body metaprofiles.

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Detects A/B chromatin compartments from balanced Hi-C contact matrices via eigenvector decomposition of the distance-normalized, Pearson-correlated cis matrix with cooltools (eigs_cis), then orients (phases) the compartment eigenvector against a GC or gene-density track so the active (A) sign is not arbitrary. Covers the eigenvector-is-a-choice problem (per-arm view_df to remove the centromere gradient; picking the eigenvector by max correlation with activity, not by eigenvalue), GC phasing with bioframe.frac_gc, resolution choice (100kb-1Mb), saddle plots and saddle_strength for compartmentalization strength, the cohesin-loss-strengthens-compartments result, subcompartments (SNIPER/Calder/dcHiC), and cross-condition compartment switching. Use when calling A/B compartments, computing E1/eigenvectors, phasing the eigenvector, building saddle plots, choosing a compartment resolution, quantifying compartment strength, or comparing compartmentalization across conditions.

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Performs set operations on genomic intervals - intersect (-wa/-wb/-wo/-wao/-loj/-c/-v/-u), subtract (-A), merge (-d, -c/-o), complement, cluster, multiinter, unionbedg, map, and groupby - with bedtools (CLI) and pybedtools/pyranges/bioframe (Python). Covers the sorted-input contract and the -sorted chromosome-order footgun, reciprocal/fractional overlap (-f/-F/-r/-e) and the A-vs-B asymmetry, -split for spliced/BED12/BAM features, and jaccard/fisher as mechanics only. Use when finding overlapping or unique regions between BED/peak/feature files, building consensus peaksets, removing blacklisted regions, transferring annotation values onto intervals, or computing interval-set similarity; route overlap-significance testing to overlap-significance.

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Analyzes pooled CRISPR screens with MAGeCK (Li et al 2014), covering count generation (mageck count), the RRA two-condition workflow (mageck test using alpha-RRA over per-sgRNA negative-binomial p-values), the MLE multi-condition workflow (mageck mle with explicit design matrix and beta-score output), normalization choice (median vs total vs control-sgRNA vs spike-in), sgRNA efficiency injection, paired-sample testing, time-course design, drug-screen versus dropout-screen design matrices, MAGeCKFlute and MAGeCK-VISPR downstream visualization, and decision logic for when to use MAGeCK vs JACKS / BAGEL2 / drugZ / Chronos. Use when running a fresh CRISPR screen analysis, picking RRA vs MLE for the experimental design, choosing a normalization method from QC signatures, debugging MLE convergence failure or NaN beta scores, comparing MAGeCK output across tools, or building a batch-aware multi-cell-line / multi-condition MLE design matrix.

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Add p-value brackets, significance asterisks, and effect-size annotations to distribution plots using ggpubr, ggsignif, and statannotations with correct test selection (parametric vs non-parametric vs paired), multiple-testing adjustment, and rendering of negative results. Use when a boxplot/violin/raincloud needs in-figure statistical comparisons between groups.

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Build volcano and MA plots from differential-expression / association results with LFC shrinkage, FDR-adjusted thresholds, sensible label placement, and axis-truncation conventions. Covers EnhancedVolcano, ggplot2, matplotlib, and the apeglm/ashr/normal shrinkage decision. Use when visualizing differential-expression results (RNA-seq, ChIP-seq, ATAC-seq, proteomics) or any per-feature effect-size + p-value table.

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Identify recurrent and driver copy number alterations across a tumor cohort with GISTIC2 (G-score, Ziggurat deconstruction, focal vs broad/arm-level analysis, q-values from permutation) and quantify copy-number signatures with the Steele 2022 COSMIC framework and the Drews 2022 CINSignatures framework. Covers driver-gene localization from recurrence peaks, distinguishing focal drivers from arm-level passengers, and the caller-sensitivity caveats of copy-number signatures. Use when finding recurrently amplified or deleted regions in a cohort, localizing driver genes, separating focal from broad events, running GISTIC2, or extracting copy-number mutational signatures.

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Run remote BLAST searches against NCBI servers using Biopython Bio.Blast.NCBIWWW. Use when identifying unknown sequences, finding homologs, picking the correct BLAST program (blastn/blastp/blastx/tblastn/tblastx/psiblast/megablast/dc-megablast), interpreting Karlin-Altschul E-values, avoiding the max_target_seqs trap (Shah 2019), choosing composition-based statistics, or limiting searches by organism. Covers RID lifecycle, database choice (nt/nr/refseq_select/swissprot), word-size and CBS taxonomy.

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Use when building PHP applications with modern PHP 8.3+ features, Laravel, or Symfony frameworks. Invokes strict typing, PHPStan level 9, async patterns with Swoole, and PSR standards. Creates controllers, configures middleware, generates migrations, writes PHPUnit/Pest tests, defines typed DTOs and value objects, sets up dependency injection, and scaffolds REST/GraphQL APIs. Use when working with Eloquent, Doctrine, Composer, Psalm, ReactPHP, or any PHP API development.

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Use when working with domain models, aggregates, value objects, domain events, or repositories in a DDD-style project. Ensures rich domain model over anemic CRUD.

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Guide for when to use and when not to use return validators in Convex functions. Use this skill whenever the user is writing Convex queries, mutations, or actions and needs guidance on return value validation. Also trigger when the user asks about Convex type safety, runtime validation, AI-generated Convex code, Convex AI rules, Convex security best practices, or when they're debugging return type issues in Convex functions. Trigger this skill when users mention "validators", "returns", "return type", or "exact types" in the context of Convex development. Also trigger when writing or reviewing Convex AI rules or prompts that instruct LLMs how to write Convex code.

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Designs and improves onboarding flows, empty states, and first-run experiences to help users reach value quickly. Use when the user mentions onboarding, first-time users, empty states, activation, getting started, or new user flows.

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Manage secrets using Azure Key Vault Secrets SDK for JavaScript (@azure/keyvault-secrets). Use when storing and retrieving application secrets or configuration values.

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Azure Tables SDK for Python (Storage and Cosmos DB). Use for NoSQL key-value storage, entity CRUD, and batch operations.

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Azure App Configuration SDK for Java. Centralized application configuration management with key-value settings, feature flags, and snapshots.

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Use by any agent before writing specs, editing code, or changing workflow files when the change could add compatibility behavior, aliases, silent fallbacks, or default-value fallbacks.

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Accessibility implementation guide for SwiftUI apps. Use when implementing VoiceOver support, adding accessibilityLabel/Hint/Value, supporting Dynamic Type, ensuring color contrast, testing accessibility, or reviewing accessibility in PRs. Covers iOS accessibility APIs, WCAG guidelines, and testing tools.

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Map observed site vegetation, species lists, land-cover descriptions, or plant management PFTs to EcoSIM vegetation codes using templates/ecosim_pftpar_20260303.nc.cdl. Use when choosing or validating EcoSIM pft_type values, pfts entries, pfts_short categories, pfts_long plant type meanings, or the combined short-code plus Koppen climate numerical code used by plant management inputs.

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Use this skill when you need to derive, from web-sourced evidence, typical values for a named plant's annual GPP, LAI, specific LAI or specific leaf area, Rubisco Vcmax at 25oC, Jmax at 25oC, root-to-shoot ratio, rooting depth, leaf protein nitrogen, and leaf chlorophyll nitrogen.

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Extract one EcoSIM PFT parameter record from a PFT-parameter NetCDF file into a standalone NetCDF. Use when Codex needs to isolate all parameters for a given EcoSIM six-character PFT code such as ndlf34, or a four-character pfts_short value plus Koppen climate code, while preserving all non-PFT-specific variables such as pfts_short, pfts_long, and Koppen metadata.

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Read-only sanity-check of EcoSIM plant_trait.*.desc parameter values for the first grid. Use when validating plant trait description files, enforcing clean C3/C4 physiological parameterization, reviewing photosynthetic kinetics, active leaf/root protein allocation, and root hydraulics such as RSRR, RVSR, and ARSRA, or checking ranges, units, and woody/herbaceous block consistency before running EcoSIM. Never edit or replace the `.desc` file.

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Edit EcoSIM PFT-parameter NetCDF files such as ecosim_pftpar_20260303.nc with the ParEditor class from applications/notebooks/scripts/ParamEditor.py. Use when asked to modify, scale, copy, compare, or delete PFT parameter records for a plant functional type (six-character pfts code such as gr3s43 or ndlf34), update microbe parameter NetCDF values, or maintain the JSONL change log that records past parameter changes. Never modify plant_trait.*.desc files; they are read-only references.

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