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Structures biological experiments so inference is valid by construction, covering Fisher's principles (randomization, replication, local control), the experimental-vs-observational unit distinction and pseudoreplication (Hurlbert 1984; Lazic 2018), randomization mechanics (complete, restricted, stratified, rerandomization, run-order), blocking layouts (randomized complete block, Latin square, incomplete block), factorial designs and interactions, and the split-plot/nested error strata hidden inside multi-batch genomics. Use when deciding the experimental unit and what counts as a replicate, planning randomization and run order, choosing a blocked/factorial/split-plot/nested layout, avoiding pseudoreplication in cell-culture or animal studies, or specifying the random-effects structure of the analysis model. For assigning samples to sequencing batches/lanes/plates and batch-effect correction see experimental-design/batch-design; for regulated clinical-trial randomization see clinical-biostatistics.

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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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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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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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Identify differentially bound regions across CLIP-seq conditions (knockdown vs control, treatment vs vehicle, disease vs healthy) using DEWSeq (sliding-window DESeq2), Flipper (Skipper-downstream), ASpeak, edgeR, or limma-voom. Use when computing condition-level changes in RBP binding intensity, choosing peak-level vs window-level vs crosslink-level testing, designing replicate experiments, or distinguishing biological binding shifts from technical confounders.

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Predict RBP binding from RNA sequence using deep learning models (RBPNet sequence-to-signal, RNAProt RNN, GraphProt2 GCN with structure, DeepCLIP, DeepRiPe multi-modal CNN) for variant-effect prediction, in silico binding-site discovery, model interpretation, and transfer learning from CLIP and RBNS datasets. Use when computational prediction of RBP binding from sequence is needed, evaluating variant effects on binding without further wet-lab experiments, comparing model performance, or training a custom model on ENCODE eCLIP data.

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Visualizes ChIP-seq data using deepTools (computeMatrix, plotHeatmap, plotProfile, bamCoverage, bamCompare), pyGenomeTracks (modern INI-driven track plots), Gviz (R browser-style), EnrichedHeatmap (ComplexHeatmap-based), ChIPseeker tag heatmaps, and IGV batch screenshots. Handles bigWig normalization choices (CPM, BPM, RPGC, spike-in scaled), bamCompare operations (log2 ratio, subtract) with SES scaling, k-means clustering of heatmaps for biological subgrouping, and spike-in-scaled tracks for global-shift experiments. Use when generating publication-quality ChIP-seq signal heatmaps, profile plots, genome-browser tracks, or comparing samples visually.

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Autonomously improve a real artifact (code, training recipe, agent harness, data pipeline, prompt) against an objective and an evaluator, using Hypothesis Tree Refinement (HTR) from the Arbor paper. Use this whenever someone wants to iteratively optimize something over many experiments without overfitting — e.g. "get my model's eval score up", "improve this agent/harness", "tune this pipeline", "beat the baseline on this benchmark", "run a search over approaches and keep the best", "do an MLE-bench / Kaggle-style optimization", or any long-horizon "make this artifact better and don't just memorize the dev set" task. Trigger it even when the user doesn't say "Arbor" or "hypothesis tree" but describes repeated experiment-and-evaluate loops, branching exploration of competing ideas, or worries about a dev/test gap. Runs Claude itself as the coordinator with subagent executors in isolated git worktrees; for the standalone `arbor` CLI tool see references/arbor-upstream.md.

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How to use the Adaptyv Bio Foundry API and Python SDK for protein experiment design, submission, and results retrieval. Use this skill whenever the user mentions Adaptyv, Foundry API, protein binding assays, protein screening experiments, BLI/SPR assays, thermostability assays, or wants to submit protein sequences for experimental characterization. Also trigger when code imports `adaptyv`, `adaptyv_sdk`, or `FoundryClient`, or references `foundry-api-public.adaptyvbio.com`.

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W&B: log ML experiments, sweeps, model registry, dashboards.

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Throwaway experiments to validate an idea before build.

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Diagnose an uncertain bug by designing experiments that distinguish competing causes, especially speculative cache, timing, environment, or concurrency explanations.

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Prices research, tests, surveys, dashboards and experiments before running them, by computing how much the result would raise expected utility - which is zero whenever no outcome would change the decision. Use when someone proposes an A/B test, user survey, market study, competitor analysis, analytics build, consultant, pilot, or "let's gather more data", and when deciding how large a study needs to be.

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Analyze, design, write, revise, translate, and review empirical or technical research papers through an evidence-bounded dialectical workflow. Use when Codex must develop a research question, integrate reference papers with a user's ideas, build phenomenon-mechanism-conditions reasoning, design methods or experiments, restructure or edit a manuscript, translate Chinese academic text into restrained English, answer reviewers, or run multi-round peer-review convergence without fabricating evidence.

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Use when diagnosing agent benchmarks or runtime failures from trajectories instead of aggregate pass rates. Builds shared action-observation decision landscapes, identifies productive cores and trap regions, profiles Access/Trap/Repair behavior, and designs conservative trap-triggered recovery experiments.

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Track Two / internal innovation system for running small, fast experiments outside the core business. Runs in three modes — Diagnostic for designing the full Protoloop from scratch (intake channels, loop structure, team, exit paths), Review for running the monthly heartbeat meeting (loop-by-loop decisions, forward-loading, portfolio health), and Alert Triggers for defining tripwires that protect, feed, and maintain momentum in the system. Updates company-context.md after every run. Triggers on questions about innovation pipelines, intrapreneurship, Track Two strategy, experimentation systems, handling ideas that don't fit the core business, or building systematic exploration alongside exploitation. Based on 20 years of practice by Eterdis (eterdis.com).

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W&B: log ML experiments, sweeps, model registry, dashboards.

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Throwaway experiments to validate an idea before build.

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Use for A/B experiments on OpenAmer configs and skills.

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Knowledge base from the NIST/SEMATECH e-Handbook of Statistical Methods (NIST HB 151) — the practical statistics reference for engineering, metrology, and quality. Use for: exploratory data analysis and the four univariate assumptions (4-plot); measurement process characterization including bias/precision, calibration designs, gauge R&R, and ISO/GUM uncertainty budgets; production process characterization (stability vs. capability); process modeling and regression (LS/WLS/NLS/LOESS); design of experiments (screening, fractional/factorial, response-surface, Taguchi); statistical process control (Shewhart/CUSUM/EWMA charts, capability indices, acceptance sampling); product/process comparisons (hypothesis tests and confidence intervals for 1/2/3+ groups, ANOVA, multiple comparisons); and reliability (lifetime & repair-rate models, accelerated testing, reliability growth). Scope limits: this is applied frequentist statistics for measurement and quality — it does NOT reproduce the per-distribution formula galleries, worked case studies, datasets, plot images, or Dataplot/R code of the original web Handbook (those are described, not copied); it is thin on modern machine learning, Bayesian methods beyond conjugate reliability priors, time-series/forecasting, and Bayesian experimental design.

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Knowledge base from the DoD Test & Evaluation Enterprise Guidebook (OUSD R&E, August 2022). Use for DoD test and evaluation (T&E) across the Adaptive Acquisition Framework — the four test communities (contractor testing, developmental DT&E, operational OT&E, live-fire LFT&E); the five operational events (Operational Demonstration, EOA, OA, IOT&E, FOT&E) and the OTRR gate; the T&E Strategy / TEMP and its IDSK, with the upstream documents that feed it and the test plans that decompose it; the T&E organizations and oversight roles (USD(R&E), DOT&E, TRMC, the Service Executives and OTAs, the T&E WIPT, CDT); and pathway-specific T&E for all six acquisition pathways (Urgent Capability, Middle Tier, Major Capability, Software, Defense Business Systems). Statutory anchors include 10 U.S.C. §4171 (IOT&E) and §4172 (LFT&E/FUSL). This is guidance, not policy: it points outward to DoDI 5000.89 and the DoDI 5000-series for binding detail, and is thin on detailed test statistics/design-of-experiments methodology, cost estimating, the Acquisition of Services pathway, and any CUI/CAC-gated companion guides.

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Query PostHog product analytics via REST API — event analytics, HogQL SQL queries, feature flags, experiments, session recordings, insights, persons, cohorts. Use when the user wants to answer an analytics question, toggle/inspect a flag, or pull event data programmatically without opening the PostHog UI or installing the PostHog MCP.

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Improve conversion performance on marketing pages and forms through diagnosis, message hierarchy, friction analysis, proof, UX hypotheses, instrumentation and experiments.

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Design valid marketing experiments with hypotheses, primary metrics, guardrails, sample/traffic assumptions, implementation QA and decision rules.

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