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Simulate transcription factor perturbation effects on cell state in silico with CellOracle and Dynamo, and predict transcriptional responses to genetic perturbations with GEARS, scGen, and CPA. Covers the direction-not-magnitude principle, local-linear validity, the GRN/velocity error it inherits, baseline discipline (mean and additive baselines), and the validation gap. Use when predicting TF knockout or overexpression effects, ranking driver TFs for fate transitions, or planning perturbation experiments. For GRN construction see multiomics-grn; for experimental Perturb-seq see single-cell/perturb-seq.

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Designs genomics experiments so technical nuisance variation (batch, lane, plate, flow cell, operator, reagent lot, processing day) is balanced against the biological variable of interest and therefore estimable rather than confounded, using constrained sample-to-batch assignment (designit, OSAT), the confounder/mediator/collider distinction, and the principle that no post-hoc correction recovers a fully confounded design. Covers detecting hidden batches with surrogate variable analysis, a decision table for downstream correction (ComBat-seq, RUVSeq, SVA) whose execution is deferred to differential-expression/batch-correction, and reproducibility metadata. Use when assigning samples to sequencing batches/lanes/plates, avoiding batch-condition confounding, deciding whether a design is salvageable by correction, choosing a correction method, or estimating the number of hidden batches. For the experimental unit, randomization, and blocking concepts see experimental-design/randomization-blocking.

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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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Build genome-browser-style multi-track figures with pyGenomeTracks (config-driven), Gviz (R), and IGV batch screenshotting. Covers BigWig coverage tracks, BED/peak overlays, gene-model rendering, Hi-C matrix tracks, BedPE link arcs, spike-in-aware normalization, and the bamCoverage --normalizeUsing trap. Use when producing publication figures of genomic loci with stacked aligned tracks (coverage, peaks, genes, interactions) for ChIP-seq, ATAC-seq, RNA-seq, Hi-C, or generic locus visualization.

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Detect, date, and contextualize whole-genome duplication (WGD / paleopolyploidy) events using wgd v2 (Chen et al 2024), KsRates (Sensalari 2022 substitution-rate-corrected Ks dating), DupGen_finder (Qiao 2019), MAPS (Li 2018 phylogenomic), POInT (Conant 2008 ordered-block), SLEDGe (2024 ML-based), Whale.jl (Bayesian DL+WGD), and synteny-anchored paranome construction. Use when identifying ancient polyploidy from Ks distributions and synteny block analysis, positioning WGD events relative to speciation, distinguishing tandem from segmental from WGD duplications, dating the 2R/3R vertebrate / fish / salmonid WGDs, building paranome and Ks-age mixture models, applying KsRates substitution-rate correction across lineages, or testing alternative biased-fractionation / dosage-balance models post-WGD.

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Corrects the gene-independent copy-number artifact in CRISPR-Cas9 screens (Aguirre 2016 / Munoz 2016 Cancer Discov) where amplified loci appear essential from DNA-damage burden of simultaneous cuts. Covers the gene-independent DNA-damage / G2-arrest mechanism, CRISPRcleanR (Iorio 2018) unsupervised pre-hoc correction, CERES (Meyers 2017) joint CN + gene-effect model, Chronos (Dempster 2021) DepMap-standard population-dynamics + CN model with lowest residual bias, the decision tree by data availability, the Spearman LFC-vs-CN diagnostic, focal-amplification examples (ERBB2 in HER2+, MYC in colorectal, FGFR1 in head and neck), and CRISPRi/a alternatives that bypass the artifact. Use when screening cancer cell lines, diagnosing essentiality at amplified loci, choosing CRISPRcleanR / CERES / Chronos, deciding whether CN correction is needed before MAGeCK / BAGEL2 / drugZ, or switching from Cas9 to CRISPRi.

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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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Performs gene-level association from GWAS summary statistics via genetically predicted tissue expression using FUSION, PrediXcan, S-PrediXcan, S-MultiXcan, UTMOST, MOSTWAS, kTWAS, EpiXcan, TIGAR-V2, and probabilistic fine-mapping with FOCUS and MA-FOCUS. Use when running TWAS from GWAS sumstats, prioritising candidate causal genes from a GWAS lead locus, picking single-tissue vs cross-tissue models, identifying LD-induced TWAS false positives, choosing ancestry-matched prediction weights, fine-mapping co-regulated TWAS hits, or triangulating TWAS with cis-eQTL Mendelian randomization and colocalization to nominate a causal gene.

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Treats a ctDNA assay as a molecule-counting experiment at the Poisson edge and builds its analytical-validation case the measurement-science way. Covers the genome-equivalent currency (~330 haploid copies/ng), the lambda = input_GE x VAF sampling ceiling (lambda>=3 for ~95% detection), the error-suppression ladder (raw NGS ~1e-3 -> single-strand UMI ~1e-4/1e-5 -> duplex <1e-7), the CLSI EP17 LoB/LoD/LoD95/LoQ framework, the per-locus-vs-panel-integrated LoD distinction that lets bespoke MRD reach ppm, contrived/SEQC2 reference standards, and honest LoD reporting conditioned on input mass + consensus depth + replicate detection rate. Use when stating or trusting a sensitivity claim, designing a dilution-series validation, deciding how many genome equivalents are needed at a target VAF, choosing a single-locus vs panel-integrated LoD, or auditing a "detects 0.1% VAF" claim.

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Observe the user's screen via screenpipe, detect repeated research workflows, match them against existing scientific-agent-skills, and draft new skills (or composition recipes that chain existing ones) for the patterns not yet covered. Use when the user asks to analyze their recent work and propose skills based on what they actually do. Requires the screenpipe daemon (https://github.com/screenpipe/screenpipe) running locally on port 3030 — the skill has no other data source and will refuse to run if screenpipe is unreachable. All detection runs locally; only redacted cluster summaries reach the LLM.

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Session-scoped edit restriction: blocks Edit/Write outside an allowed path, to scope changes to one module or prevent unrelated fixes. NOT for blocking destructive shell commands (mk:careful).

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Use when a plan directory (plan.md + phase-*.md) needs a visual review. By DEFAULT this drives the STRUCTURED visual-plan artifact (visual-plan/plan.json) via the mewkit visual-plan CLI — generate if absent, validate, open the local studio (view/edit), and export plan.html from the approved artifact. Pass --static for the legacy prompt-only single-file plan.html template render. Triggers on "render this plan", "visualize the plan", "open the plan studio", "make a shareable plan page", "plan.html". This is the canonical owner of plan-as-visual-review. NOT for plan critique or scope review (see mk:plan-ceo-review / mk:validate-plan), NOT for generic code/diagram/diff visuals (see mk:preview), NOT for live media generation (see mk:multimodal).

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Serve any markdown file or directory as a calm, book-like reader via a local HTTP server (127.0.0.1 only). Best for long-form documents — RFCs, runbooks, design docs, plan files — where comfortable in-browser reading matters. Supports Mermaid diagrams, dark/light mode, plan navigation sidebar, and keyboard shortcuts. Requires explicit start and stop lifecycle.

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Use RoutIR — call a running endpoint with the client, stand up a local server that mixes locally-hosted services with services proxied from a remote master server, and extend RoutIR with new bi-encoders, rerankers, and document collections by writing a small config (and optionally one Python file referenced via `file_imports`). No checkout of the routir source is required.

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Search cloud memory backup when local results are insufficient. Use when memory_search returns few/no results for a topic you know was discussed before. Cloud preserves everything - even memories that were deleted or compacted locally.

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Scientific model and eval tuning loop for prompt/skill/system-prompt changes, model configuration, runtime options, and local/Ollama model sizing or environment variables. Use when tuning eval performance, comparing local or remote models, improving tool-use behavior, reducing timeouts/loops, or deciding whether an eval optimization is worth keeping.

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Turn on Cache Components in a Next.js app and resolve the blocking routes it surfaces. Use when the user wants to enable, adopt, or migrate to Cache Components, flip the `cacheComponents` flag, work through a flood of blocking-prerender / instant validation errors, run the `cache-components-instant-false` codemod, or decide between opting routes out with `export const instant = false` and fixing them in place.

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Apply when creating, modifying, or reviewing any Rembric agent plugin. Triggers on changes under `apps/plugin/`, on new clients added alongside Claude Code / Codex CLI / Hermes Agent / opencode / Pi, on edits to `apps/plugin/mcp-bridge/`, `apps/plugin/bin/rembric-plugin-core.mjs`, per-client manifest changes, or plugin install/uninstall scripts. End-to-end validation against a local dev server (`pnpm run dev`, host Next.js on :3000) is mandatory whenever local testing is feasible.

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This skill should be used when the user asks about "plugin settings", "store plugin configuration", "user-configurable plugin", ".local.md files", "plugin state files", "read YAML frontmatter", "per-project plugin settings", or wants to make plugin behavior configurable. Documents the .claude/plugin-name.local.md pattern for storing plugin-specific configuration with YAML frontmatter and markdown content.

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This skill recommends against initiating puberty blocking or gender-affirming hormone treatment in prepubertal children diagnosed with gender dysphoria or gender incongruence. Clinical triggers include a young child presenting with GD/gender incongruence and caregivers or clinicians considering hormone intervention.

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This skill suggests medical therapy to block aberrant hormone receptors for bilateral macronodular adrenal hyperplasia (BMAH) when surgery is not preferred or feasible. Consider this approach in patients with confirmed BMAH and evidence of aberrant hormone receptor expression (e.g., GIP, LH/hCG, serotonin) driving cortisol excess.

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This skill recommends localizing and resecting ectopic ACTH-secreting tumors with node dissection when ectopic ACTH secretion is suspected or confirmed. Clinical triggers include unexplained persistent hypercortisolism after pituitary surgery, elevated ACTH with negative pituitary MRI, or identification of occult ectopic ACTH syndrome (EAS) on biochemical testing.

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Suggests a trial of dehydroepiandrosterone (DHEA) replacement in women with primary adrenal insufficiency (PAI) who report low libido, depressive symptoms, and/or low energy levels despite otherwise optimized glucocorticoid and mineralocorticoid replacement. Consider when a woman with PAI presents with persistent low libido, depressive symptoms, and/or low energy levels after glucocorticoid and mineralocorticoid doses have been titrated to clinical targets.

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This skill recommends simultaneous measurement of plasma renin and aldosterone in patients with primary adrenal insufficiency (PAI) to determine the presence of mineralocorticoid deficiency. It is triggered when assessing for mineralocorticoid deficiency in PAI, such as in patients with unexplained hyponatremia, hyperkalemia, or salt craving despite glucocorticoid replacement.

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