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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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Processes eDNA metabarcoding from raw paired-end reads to species tables, navigating ASV (DADA2, UNOISE3) vs OTU (swarm v2) decision (Callahan 2017 vs Schloss multi-copy-16S critique), marker/primer choice (Leray COI, MiFish 12S, 515F/806R 16S, ITS2) with primer-specific bias, OBITools3 v3 command-name break (obi stats plural; .tar.gz taxonomy), tag-jumping with dual-indexing (Schnell 2015; NovaSeq 10x MiSeq), decontam as screening-not-classifier (Davis 2018), read-counts-not-abundance critique (Lamb 2019), site-occupancy modeling (Ficetola 2015), Naive-Bayes calibration limits (Bokulich 2018), and eDNA decay (Strickler 2015). Use when going from raw eDNA FASTQ to species tables, picking marker + denoising pipeline, deciding whether read counts represent abundance, applying occupancy modeling, configuring OBITools3 v3, or interpreting decontam output. Not for clinical 16S microbiome (see microbiome/amplicon-processing).

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Download raw sequencing reads from NCBI SRA using sra-tools (prefetch, fasterq-dump, vdb-validate) or the ENA mirror. Use when pulling FASTQ for SRR/ERR/DRR accessions, deciding between SRA-direct, ENA mirror, or AWS/GCP cloud mirror (STRIDES), handling --include-technical for 10x and other single-cell records, validating with MD5/vdb-validate, navigating SRR/SRX/SRS/SRP/PRJNA hierarchy, or finding accessions via pysradb. Encodes SRA cloud-egress economics, the fasterq-dump uncompressed-scratch trap, and the --max-size default that silently truncates large prefetches.

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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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Classify constitutional (germline) copy number variants for clinical reporting using the 2019 ACMG/ClinGen technical standards points-based framework, with ClassifyCNV and AnnotSV for semi-automated scoring. Covers the separate copy-number-loss and copy-number-gain rubrics, the five-tier classification, ClinGen haploinsufficiency/triplosensitivity and dosage-sensitive regions, de novo and segregation evidence, and population-frequency benign evidence. Use when assigning pathogenic/likely-pathogenic/VUS/likely-benign/benign to a constitutional CNV, scoring a CNV against ACMG/ClinGen criteria, or distinguishing the automatable evidence from the case-specific evidence requiring manual input.

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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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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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Normalizes ChIP-seq data using exogenous spike-in (ChIP-Rx with Drosophila chromatin per Orlando 2014 / Egan 2016; E. coli carryover for CUT&RUN/CUT&Tag). Distinguishes RRPM from Rx-Input scaling, integrates with DiffBind / DESeq2 / edgeR / csaw via sizeFactors and DiffBind library-size vectors, applies the Patel et al 2024 *Nat Biotechnol* failure-mode framework, and validates that normalization is applied at the read level (not peak counts). Use when global signal shifts are expected (HDACi, BETi, EZH2i, dosage, target knockdown), when ChIPseqSpikeInFree detects post-hoc shifts, or when validating internal-control regions before publication.

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Analyzes alternative splicing at single-cell resolution. The first decision is library chemistry — 10X 3' is fundamentally limited (RT primes from poly-A, R2 falls in 3' UTR, <0.1 junction read per cell per AS event). Plate-based full-length methods (Smart-seq3, FLASH-seq, VASA-seq, STORM-seq) and single-cell long-read (MAS-Iso-seq, scISOr-Seq2) are the chemistries that give per-cell isoform structure. Tools include MARVEL (R, Smart-seq integrated), BRIE2 (Bayesian PSI with regulatory features and ELBO_gain test), scQuint (junction-cluster, plate-based; not for 10X), SpliZ (annotation-free Z-score), Psix (graph-smoothness regulated AS), and Sierra (alternative polyadenylation, often confused with AS). Use when analyzing isoform usage in scRNA-seq, identifying cell-type-specific splicing, or determining whether scRNA-seq chemistry supports splicing analysis at all.

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Build and audit SwiftUI, UIKit, and AppKit accessibility for VoiceOver, Voice Control, Switch Control, Full Keyboard Access, Dynamic Type, focus restoration, labels/traits/actions, traversal, custom rotors, NSAccessibility, XCTest checks, adaptive system preferences, and App Store accessibility declarations. Use when implementing accessible UI, fixing an accessibility audit, testing assistive-technology behavior, or substantiating App Store Accessibility Nutrition Labels.

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Implement iOS authentication flows with AuthenticationServices and LocalAuthentication. Use when building Sign in with Apple, passkey/WebAuthn registration or sign-in with ASAuthorizationPlatformPublicKeyCredentialProvider, ASAuthorizationController credential state and revocation handling, ASWebAuthenticationSession OAuth or third-party login, Password AutoFill, identity-token server validation, or local biometric re-authentication with LAContext.

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Use this skill whenever the user wants to create or improve a presentation for an academic context — conference papers, seminar talks, thesis defenses, grant briefings, lab meetings, invited lectures, or any presentation where the audience will evaluate reasoning and evidence. Triggers include: 'conference talk', 'seminar slides', 'thesis defense', 'research presentation', 'academic deck', 'academic presentation'. Also triggers when the user asks to 'make slides' in combination with academic content (e.g., 'make slides for my paper on X', 'create a presentation for my dissertation defense', 'build a deck for my grant proposal'). This skill governs CONTENT and STRUCTURE decisions. For the technical work of creating or editing the .pptx file itself, also read the pptx SKILL.md.

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This skill should be used when building, modifying, or debugging a react-admin application — including creating resources, lists, forms, data fetching, authentication, relationships between entities, custom pages, or any CRUD admin interface built with react-admin.

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Use when the user needs multi-source research with citation tracking, evidence persistence, and structured report generation. Triggers on "deep research", "comprehensive analysis", "research report", "compare X vs Y", "analyze trends", or "state of the art". Not for simple lookups, debugging, or questions answerable with 1-2 searches.

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Simulate Bluetooth system-level networks using the Bluetooth Toolbox. Use this skill for any Bluetooth topology: BLE ACL (Asynchronous Connection-Less) data connections, CIS (Connected Isochronous Stream) and LE Audio for stereo speakers or hearing aids, BLE GAP (Generic Access Profile) connection establishment with advertising and scanning, Classic BR/EDR piconets with ACL data and SCO (Synchronous Connection-Oriented) voice links, and BLE+BR/EDR coexistence with adaptive frequency hopping. Covers bluetoothLENode, bluetoothNode, bluetoothLEConnectionConfig, bluetoothLECISConfig, bluetoothLEGAPConfig, bluetoothConnectionConfig, configureConnection, kpi (), updateChannelList, and all Bluetooth statistics.

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Set up and run wireless network simulations using the Wireless Network Toolbox. Use this skill when creating system-level simulations with wirelessNetworkSimulator, adding traffic sources (networkTrafficOnOff, networkTrafficFTP, networkTrafficVoIP, networkTrafficVideoConference), configuring node mobility, logging events or IQ samples, visualizing traffic, scheduling actions during simulation, running parametric sweeps, writing PCAP files with pcapWriter or technology-specific PCAP writers, registering event callbacks on wireless nodes, accessing event data fields, or combining multiple capture/visualization tools in a simulation.

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Select and use Audio Toolbox acoustic, psychoacoustic, and speech quality metrics. Use when computing loudness, sharpness, roughness, fluctuation strength, noise criteria (NC/RNC/RC), speech transmission index (STI), speech intelligibility index (SII), speech quality (ViSQOL, STOI), SPL, reverberation time (RT60), tone-to-noise ratio, or prominence ratio. Also use when asked about PESQ, POLQA, calibration factor, EBU R 128, LUFS, HVAC noise, background noise evaluation, or how to measure audio quality or noise compliance. Covers calibration, standard selection, signal alignment, and the complete function inventory including what does NOT exist.

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Interpret and explain a trained tabular machine-learning model (classification or regression) in MATLAB. Find which predictors, features, or columns matter most; explain why the model made a specific prediction, including diagnosing predictions it got wrong; show how a predictor affects the output; and compare how the model behaves across cohorts or subgroups. Uses model-agnostic techniques and model-native measures, and works on custom models (such as a dlnetwork) through a prediction function handle. Use for model interpretability, explainability, and feature-importance questions on tabular data, not for training, tuning, feature selection, deploying models, or models trained on image, text, signal, or other non-tabular data.

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Perform basic penetration testing and security assessments. Use reconnaissance, vulnerability discovery, and exploitation techniques. Use when validating security controls or assessing system security.

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Apply systematic problem-solving techniques when stuck. Use for complexity spirals, innovation blocks, recurring patterns, assumption constraints, simplification cascades, scale uncertainty.

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Search library/framework documentation via llms.txt (context7.com). Use for API docs, GitHub repository analysis, technical documentation lookup, latest library features.

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Automatically creates user-facing changelogs from git commits by analyzing commit history, categorizing changes, and transforming technical commits into clear, customer-friendly release notes. Turns hours of manual changelog writing into minutes of automated generation.

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Writing effective code documentation - API docs, README files, inline comments, and technical guides. Use for documenting codebases, APIs, or writing developer guides.

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Use when running or scheduling periodic repository review cycles that must dispatch the correct reviewer, aggregate findings, and escalate outcomes into reports, issues, or corrective PRs across API contracts, documentation freshness, code quality, and CloudBase skill quality.

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