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Designs cytosine (CBE, C-to-T) and adenine (ABE, A-to-G) base-editor guides by positioning the target base at the activity-peak of the editing window (protospacer positions ~5-7, PAM-distal numbering), minimizing bystander edits for product purity, reading dinucleotide context (APOBEC1 TC favored / GC disfavored), and selecting the editor variant (BE4max, ABEmax, ABE8e, YE1/SECURE, TadCBE, CGBE, SpG/SpRY-BE). Covers knockout by premature stop (CRISPR-STOP/iSTOP) and splice-site disruption, the three off-target classes (Cas-dependent, Cas-independent DNA, RNA), outcome prediction (BE-Hive/DeepBE), and the base-vs-prime-vs-HDR decision. Use when installing a transition mutation without a double-strand break, knocking out a gene without indels, or choosing CBE vs ABE. Generic guide scoring, prime editing, and HDR donors are separate skills.

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Visualises RNA-modification data with transcript-feature metagene plots (Guitar GuitarPlot with 5'UTR / CDS / 3'UTR scaling; MetaPlotR; deepTools `computeMatrix scale-regions`), peak-centred heatmaps (ComplexHeatmap; deepTools plotHeatmap), IP-vs-input paired browser tracks (bigWig of log2 IP/input via deepTools `bamCompare`; ggcoverage; pyGenomeTracks; Gviz; IGV / UCSC track hubs), DRACH sequence-logo plots (ggseqlogo; MEME), 5'UTR / CDS / 3'UTR stacked-bar feature-distribution summaries, and volcano / MA plots for differential modification. Establishes stop-codon enrichment in the metagene plot as the biological QC anchor for any MeRIP dataset (Dominissini 2012 *Nature* 485:201; Meyer 2012 *Cell* 149:1635 — concurrent founding papers from different labs both showed this independently). Use when producing the canonical metagene plot with stop-codon enrichment as a QC anchor, building paired IP/input genome-browser tracks at single-locus resolution, plotting peak-centred heatmaps clustered by condition, summarising peak distribution across transcript features for figure 1, generating DRACH motif logos as sanity checks on the peak set, rendering volcano plots of differential m6A, or reproducing the Dominissini 2012 / Meyer 2012 stop-codon enrichment plot.

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Estimates the minimum biological replicates (or cells/events) for a target power at a target FDR in genomics experiments using ssizeRNA, PROPER, powsimR for scRNA-seq, and pilot-data dispersion estimation from DESeq2/edgeR. Covers the biological-versus-technical replication distinction (technical replicates do not add degrees of freedom for biological inference), replicate-number-versus-sequencing-depth budgeting, scRNA-seq sample-versus-cell allocation under a pseudobulk model, and the critique that "n=3" is a publication convention rather than a power calculation. Use when budgeting a sequencing experiment, writing the sample-size justification in a grant, estimating replicates from pilot data, allocating a fixed budget between samples and depth, or planning scRNA-seq cohort size. For clinical-trial sample size see clinical-biostatistics/power-and-sample-size; for the power-given-n direction see experimental-design/power-analysis.

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Identifies essential genes from CRISPR-Cas9 fitness screens using BAGEL2 (Kim & Hart 2021 Genome Med), a Bayesian classifier scoring per-gene Bayes Factors via log-likelihood ratios over per-sgRNA fold changes, calibrated against CEGv2 core-essentials (Hart 2017 G3, ~684 genes) and NEGv1 non-essentials (Hart 2014, ~927 genes). Covers the fc + bf + pr workflow, the linear-extrapolation improvement over BAGEL1 truncation, multi-target off-target correction, tumor-suppressor sensitivity (BAGEL2 detects enrichment), and BF-to-FDR calibration (BF >6 ≈ FDR 0.05 from Hart 2017). Use when classifying essential vs non-essential genes, calibrating BAGEL2 thresholds against PR curves, identifying tumor suppressors alongside essentials, comparing BAGEL2 hits to MAGeCK / drugZ, or generating publication-quality essentiality calls.

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Quantifies CRISPR editing outcomes with CRISPResso2 (Clement 2019 Nat Biotechnol) across Cas9-nuclease (indels, HDR), CBE and ABE base editors (target conversion + bystander), and prime editor (pegRNA-templated) modes. Covers single-amplicon (CRISPResso), multi-sample batch (CRISPRessoBatch), pooled-amplicon (CRISPRessoPooled), WGS off-target (CRISPRessoWGS), and sample-comparison (CRISPRessoCompare) workflows; quantification-window math that controls what is called edited; substitution-vs-indel diagnostic to distinguish BE from Cas9 contamination; MMEJ deletion pattern interpretation; allele-frequency tables; and failure modes from amplicon misalignment or contamination. Use when quantifying editing from amplicon sequencing, choosing CRISPResso mode by design, distinguishing intended edits from bystanders and indel byproducts, debugging low-alignment runs, or generating publication-grade editing reports.

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Designs and analyzes in vivo CRISPR screens in animal tumor models, organoids, and immune-cell adoptive transfers. Covers bottleneck math (250x cells/sgRNA requires ~25M cells implanted; impossible for most syngeneic models, forcing focused libraries), focused library design (Manguso 2017 Nature 547:413 immune screen; Chen 2015 tumor screens), CRISPR-StAR intrinsic-control screening (Uijttewaal 2025 Nat Biotechnol 43:1848), clonal-dynamics-limited detection, tumor-explant DNA recovery, syngeneic vs xenograft vs PDX considerations, and the relationship to downstream MAGeCK / drugZ analysis. Use when designing in vivo CRISPR screens for tumor / immune / metastasis biology, choosing focused vs genome-wide for animal models, addressing bottleneck-induced clonal collapse, picking the syngeneic / xenograft / PDX model, integrating in vivo with in vitro results, or applying CRISPR-StAR for animal experiments.

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Designs pooled sgRNA libraries for CRISPR knockout, interference (CRISPRi), activation (CRISPRa), Cas12a multiplex, base-editor, and prime-editor screens. Covers on-target scoring (Rule Set 2, Azimuth, DeepSpCas9, CRISPRon), off-target scoring (CFD, MIT), TSS-relative positioning for CRISPRi/a (Horlbeck, Dolcetto, Calabrese), PAM-variant chemistries, control-guide composition, oligo cloning architecture, and library QC. Use when choosing a genome-wide library (GeCKOv2 vs Avana vs Brunello vs TKOv3 vs Inzolia), designing a focused or paralog-focused custom library, picking CRISPRi vs CRISPRa TSS windows, deciding control-guide proportions, or diagnosing library skew and dropout in a freshly cloned pool.

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Queries PharmGKB / CPIC / DPWG for drug-gene interactions; calls CYP2D6/CYP2C9/CYP2C19/DPYD/TPMT/NUDT15/UGT1A1/SLCO1B1 star alleles and phenotype with PharmCAT, Cyrius (CYP2D6 structural variants), Aldy, Stargazer; applies Caudle 2020 activity-score translation. Use when implementing pharmacogenomic-guided prescribing, applying CPIC vs DPWG guidance, screening HLA risk alleles for ICI / antiepileptics / abacavir, or interpreting compound TPMT+NUDT15 thiopurine risk.

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Align preprocessed CLIP-seq reads (eCLIP, iCLIP, iCLIP2, PAR-CLIP) to genome with STAR or bowtie2 using crosslink-preserving parameters, choosing between unique-mapper-only and multi-mapper-aware alignment for repeat-binding RBPs, deciding STAR vs HISAT2 memory trade-offs, and applying ENCODE-compatible filters. Use when turning preprocessed CLIP FASTQ into a deduplicated, MAPQ-filtered BAM ready for peak calling or crosslink-site detection.

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Designs covalent inhibitors and warheads targeting cysteine (most common, 98% of covalent drugs), lysine, serine, threonine, tyrosine, and aspartate residues, with explicit handling of warhead reactivity (acrylamide, chloroacetamide, vinyl sulfone, sulfonyl fluoride, fluorosulfate, aldehyde, boronate, nitrile), reversibility (kinact/Ki, t_residence), glutathione (GSH) stability, intrinsic reactivity assays, and covalent docking (DOCKovalent, GOLD, HCovDock). Use when designing covalent inhibitors for targeted covalent inhibition (TCI), KRAS G12C-style approaches, or rationalizing covalent SAR.

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Predict enhancer-gene regulatory connections from ATAC-seq using ABC, ENCODE-rE2G, HiChIP, or Cicero. Use when linking distal enhancers to target genes, choosing between contact-aware (ABC, ENCODE-rE2G), accessibility-only (Cicero), and orthogonal (HiChIP H3K27ac, EpiMap) approaches, validating predictions against CRISPRi-FlowFISH gold-standard, or building cell-type-specific regulatory maps for fine-mapping or therapeutic target discovery.

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Audita calidad de código Kotlin/Spring Boot en este proyecto. Úsalo cuando el usuario pida revisar código, verificar estándares, hacer un code review, auditar calidad, ejecutar linters, verificar cobertura, o antes de hacer commit/PR. También úsalo cuando mencionen KTLint, Detekt, JaCoCo, cobertura, o simplemente digan "revisa el código" / "está listo para commit" / "qué tan bueno está el código".

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新しいフックの雛形（スクリプト + 配線）を本リポジトリの規約どおりに生成する。 イベント選定（PreToolUse / PostToolUse / Stop / SessionStart 等）とブロッキング可否を対話的に決め、 ai-agents/hooks/ か ai-agents/settings/<cli>/hooks/ への配置と、hooks.json / settings.json への配線まで行う。 新しいフックを追加したいときに `/hook-scaffold <フック名> [用途の一言]` で呼び出す。

Extract typical annual GPP, annual evapotranspiration, mid-season LAI, mid-season root biomass, mid-season shoot biomass, median canopy height, maximum primary-root depth, Vcmax at 25oC, and Jmax at 25oC from EcoSIM h0 NetCDF output files. Use when asked to derive these EcoSIM output targets from a selected .ecosim.h0.*.nc file for model-output processing, trait checks, or benchmark summaries.

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Guide users through the get started setup and Chrome DevTools demo.

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Extrai o brand kit do Figma — tokens de cor, tipografia, grid, logo e componentes — e grava na seção 3 do contexto. Use quando o usuário disser "extrair a marca", "pegar os tokens", "quais as cores", "design system", "importar do Figma", "montar brand kit", ou quando a seção 3 estiver vazia. Lê do Figma; não inventa paleta.

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Define, documenta e aplica a voz da marca — formalidade, personalidade, vocabulário preferido, palavras proibidas e tratamento do leitor. Use quando o usuário disser "voz da marca", "tom de voz", "brand voice", "guia de estilo", "padronizar o tom", "não parece nossa marca", "manual de redação", ou quando precisar auditar se um texto está aderente. Extrai a voz de amostras reais em vez de inventar adjetivos, e grava o resultado na seção 5 de .claude/pwdev-copy-context.md para todas as demais skills consumirem.

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Copy para setor público e saúde — linguagem cidadã, acessibilidade, LGPD e comunicação de política pública. Use quando o contexto for prefeitura, secretaria, SUS, assistência social, transparência ou governo digital, ou quando o usuário citar DashSaúde, Integra Arapiraca, ODARA, e-SUS ou APS.

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Scaffold a minimal GNOME-compliant GTK4/libadwaita app from scratch — window, header bar, ViewSwitcher, adaptive breakpoint, menu, preferences, GSettings schema, desktop entry, meson. Use when starting a new GNOME app or when the user asks for a GNOME app template.

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When the user wants to create or update their product marketing context document. Also use when the user mentions 'product context,' 'marketing context,' 'set up context,' 'positioning,' 'who is my target audience,' 'describe my product,' 'ICP,' 'ideal customer profile,' or wants to avoid repeating foundational information across marketing tasks. Use this at the start of any new project before using other marketing skills — it creates `.agents/product-marketing-context.md` that all other skills reference for product, audience, and positioning context.

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When the user wants to audit, review, or diagnose SEO issues on their site. Also use when the user mentions "SEO audit," "technical SEO," "why am I not ranking," "SEO issues," "on-page SEO," "meta tags review," "SEO health check," "my traffic dropped," "lost rankings," "not showing up in Google," "site isn't ranking," "Google update hit me," "page speed," "core web vitals," "crawl errors," or "indexing issues." Use this even if the user just says something vague like "my SEO is bad" or "help with SEO" — start with an audit. For building pages at scale to target keywords, see programmatic-seo. For adding structured data, see schema-markup. For AI search optimization, see ai-seo.

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Static-to-EDS conversion that preserves the original design while making content authorable in Document Authoring. Two modes — page-level (overlay template with slot markers) and block-level (each section becomes an independent EDS block). Use when converting an AI-generated static HTML page (Stardust, Mobirise, Relume, Lovable, v0, Figma-derived hand-coded, etc.) into an Edge Delivery Services page. Triggers on "convert this page to EDS", "static-to-EDS overlay", "convert to EDS blocks", "next experimentation", "next run", "start run", or when a user provides a source URL and asks to make it editable in DA while keeping the original design intact. Do NOT use for canonical EDS block-rewrite migrations — that's the page-import skill.

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Raw mechanical interfaces fusing Swiss typographic print with military terminal aesthetics. Rigid grids, extreme type scale contrast, utilitarian color, analog degradation effects. For data-heavy dashboards, portfolios, or editorial sites that need to feel like declassified blueprints.

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EDITOR PREVIEW SCREENSHOT SKILL — Capture the current Cocos Creator Editor window to a PNG file and inspect exactly what is already visible inside the Editor. USE FOR: visual symptoms when the user already has the target screen open in Cocos Editor / Editor Preview. DO NOT USE FOR: browser-driven QA, automatic browser target switching, reference-image comparison pipelines, compile errors, or pure log analysis. If the user wants browser screenshots, remind them to prepare the Browser Review environment and use cocos-preview-qa instead.

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