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Assesses the quality and completeness of a genome annotation with BUSCO (conserved single-copy ortholog recovery), OMArk (proteome completeness, consistency, and contamination), CheckM2 (prokaryotic completeness/contamination), and a gene-set sanity panel (gene count, mono-exonic fraction, protein-length distribution, mRNA:gene ratio, coding density). Covers the assembly-BUSCO-vs-proteome-BUSCO diagnostic, what BUSCO-Duplicated really means, why gene count is a vanity metric, and the QC of transferred annotations. Use when judging whether an annotation is good enough to publish or submit, diagnosing a suspect annotation, or comparing annotation completeness across pipelines.

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Download large datasets from NCBI efficiently using EPost, history server, batching, rate limiting, and retry logic. Use when bulk-fetching tens of thousands of sequences, pulling all results of a large ESearch, designing reproducible pipelines, comparing E-utilities to NCBI Datasets v2 CLI, or implementing checksum-validated downloads. Encodes WebEnv TTL (~8h), EPost 200-ID limit, retmax caps, parallelization design, and integrity verification.

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Profiles RNA-binding protein targets without antibody or UV crosslinking using STAMP (APOBEC1-RBP fusion, C-to-U editing), scSTAMP (single-cell), TRIBE/HyperTRIBE (ADAR-RBP, A-to-I editing), DART-seq (APOBEC1-YTH for m6A), or Bullseye/SAILOR edit-site detection pipelines. Use when antibody is unavailable or specificity is doubtful, when single-cell RBP profiling is needed (scSTAMP), or when in vivo RBP profiling without UV is preferred.

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Build whole-genome alignments using Progressive Cactus (Armstrong 2020 reference-free clade-level WGA), Minigraph-Cactus (Hickey 2024 pangenome-aware), LASTZ chain/net (UCSC pipeline), MUMmer4 (Marçais 2018 pairwise), minimap2 -x asm5/10/20 (Li 2018 fast pairwise), AnchorWave (Song 2022 WGD-aware), and Mauve / progressiveMauve (bacterial). Operates the HAL toolkit (Hickey 2013) for downstream extraction including halSynteny, halLiftover, halBranchMutations, and hal2maf. Use when constructing multi-species alignments for comparative-annotation projection (TOGA), synteny detection, conservation analyses (phyloP / PhastCons), or pangenome graph construction; selecting between reference-free (Cactus) and reference-anchored (LASTZ chains/nets) approaches; tuning sensitivity for closely vs distantly related genomes; or producing HAL files for genome-wide downstream tools.

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Analyzes base-editing screens for variant function. Covers library design (Hanna 2021 ClinVar-scale CBE screen benchmarked on BRCA1/2, Cuella-Martin 2021 DDR saturation), CBE vs ABE chemistry choice (BE3/BE4 vs ABE7.10/ABE8.20/ABE8e), editing-window math (positions 4-8 from PAM-distal end; 4-7 for ABE7.10), bystander-edit quantification and the variant-call ambiguity it creates, sgRNA-efficiency filtering before hit calling, indel byproduct interpretation, the substitution-vs-indel diagnostic, variant annotation against ClinVar / COSMIC, and the Broad be-validation-pipeline. Use when designing a BE variant screen, choosing CBE vs ABE for a specific edit, interpreting bystander-confounded hits, distinguishing functional signal from indel artifact, integrating CRISPResso2 output with screen scoring, or deciding BE vs PE for SNV installation.

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Identify direct miRNA-target interactions from AGO HITS-CLIP, AGO-CLEAR-CLIP (chimeric reads), HEAP (Halo-Ago2 mouse), chimeric eCLIP / miR-eCLIP (deep miRNA-target profiling), or CLASH using chimeric-read processing pipelines, seed-pairing analysis, and 3' auxiliary pairing rules. Use when distinguishing direct miRNA targets from indirect, integrating CLIP-derived target maps with TargetScan / miRDB / DIANA predictions, applying canonical 7mer-8mer seed matching with 3' UTR context, or recovering miRNA-mRNA chimeras at scale.

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Prioritizes rare-disease variants from trio/quad WES/WGS with de novo (DeNovoGear, Triodenovo), compound-heterozygous phasing (WhatsHap), mosaic VAF tiering, phenotype-driven ranking (Exomiser, Phen2Gene, AMELIE), ClinGen gene-disease validity gating, and ACMG SF v3.2 secondary findings reporting. Use when running diagnostic exome / genome pipelines, identifying candidate Mendelian disease genes, screening for incidental findings, or auditing VUS reclassification cycles. The ACMG/AMP classification framework (PVS1 decision tree, Pejaver PP3/BP4 calibration, Tavtigian point system) is in clinical-databases/acmg-classification.

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Resolve the architecture of focal oncogene amplifications — extrachromosomal DNA (ecDNA), breakage-fusion-bridge (BFB) cycles, homogeneously staining regions (HSR), and linear amplification — from whole-genome sequencing with AmpliconArchitect, the AmpliconSuite pipeline, and AmpliconClassifier. Covers copy-number seed selection, breakpoint-graph reconstruction, balanced-flow optimization, ecDNA classification, and the limits of depth-only amplification calls. Use when a focal amplification needs structural characterization, when distinguishing ecDNA from chromosomal amplification, suspecting ecDNA-driven oncogene amplification or therapy resistance, or selecting copy-number seeds for amplicon reconstruction.

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Standardizes molecular structures using the ChEMBL structure pipeline for normalization and parent selection plus RDKit rdMolStandardize for explicit custom steps such as tautomer canonicalization, salt/solvent stripping, charge handling, stereochemistry handling, mixture selection, and isotope normalization. Explicitly compares ChEMBL, canSARchem, RDKit, and PubChem standardization choices. Use when preparing libraries for QSAR training, joining datasets across sources, deduplicating compound collections, or building canonical compound registries.

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Performs retrosynthetic planning using AiZynthFinder (template-based MCTS), maintained or version-pinned template-free models, ASKCOS, and emerging RetroSynFormer with explicit handling of route scoring, configurable MCTS rewards, building-block availability, and forward-prediction checks. Use when assessing synthetic feasibility of generated or selected molecules, planning multi-step syntheses, building synthesis-aware design pipelines, or screening libraries for retro-route feasibility.

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Detects aberrant splicing in single rare-disease patients vs a control panel using FRASER 2.0 (Bioconductor; Beta-binomial autoencoder on Intron Jaccard Index, default delta cutoff 0.1, q hyperparameter), OUTRIDER (gene-level outlier expression via autoencoder denoising), LeafcutterMD (Dirichlet-multinomial outlier mode of LeafCutter for annotation-free junctions), and DROP (Snakemake pipeline integrating FRASER2 + OUTRIDER + monoallelic expression for clinical diagnostics). The statistical model is fundamentally different from differential splicing — single-sample-vs-cohort outlier detection rather than two-group comparison. Standard tool in EU rare-disease (Solve-RD) and NIH UDN programs. Use when applying RNA-seq to undiagnosed Mendelian disease, validating predicted splice variants in clinical samples, or detecting cryptic splicing in disease tissue.

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Analyzes differential transcript usage (DTU) and isoform switches with functional consequence prediction (NMD via 50nt rule, ORF disruption, protein domain loss/gain, signal peptide changes, IDR alterations, coding-potential shifts). Tools include IsoformSwitchAnalyzeR v2 (auto-selects satuRn for >5 reps else DEXSeq), the manual DRIMSeq -> DEXSeq/satuRn -> stageR DTU pipeline, and fishpond/swish for inferential-uncertainty-aware DTE. Distinguishes DTU from DGE and DTE; integrates external annotators (CPC2, Pfam, SignalP, IUPred2A or DeepTMHMM). Use when investigating how splicing differences alter protein function or trigger NMD-mediated degradation.

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Maintain and extend existing SceneKit 3D scenes and visualizations. Use when working with SCNView, SCNScene, SCNNode scene graphs, SceneKit geometry/materials/lights/cameras, SCNAction animation, SCNPhysicsBody physics, SCNParticleSystem effects, .scn/.dae/.abc SceneKit assets, shader modifiers, or SwiftUI SceneView. SceneKit is soft-deprecated and in maintenance mode; route new apps, significant updates, USD/USDZ pipelines, and migration planning toward RealityKit.

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Integrate Core ML models in iOS apps for on-device machine learning inference. Covers model loading (.mlmodel, .mlpackage, .mlmodelc), predictions with auto-generated classes and MLFeatureProvider, compute unit configuration (CPU, GPU, Neural Engine), MLTensor, VNCoreMLRequest, MLComputePlan, multi-model pipelines, and deployment strategies. Use when loading Core ML models, making predictions, configuring compute units, or profiling model performance.

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Runs LiveKit agent simulations and acts on the results. Use when the user says "run my simulations", "regression test my agent before deploying", "run the scenarios", "use lk agent simulate", "did my agent pass", "why did this scenario fail", "run simulations in CI", "test the audio pipeline", "check turn-taking and interruptions", or wants to check whole-conversation behavior before shipping. Covers text and audio mode and what each catches, running against a local or deployed agent, degraded-audio flags, automating a pre-release run, and triaging failures with list, view and export. For writing the scenarios use writing-livekit-scenarios. Not the default for a bare "test my agent", which goes to debugging-livekit-agents. Use this skill when the user names simulations, scenarios, a run, CI, or shipping.

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Use this skill any time a spreadsheet file is the primary input or output. This means any task where the user wants to: open, read, edit, or fix an existing .xlsx, .xlsm, .xltx, .csv, or .tsv file (e.g., adding columns, computing formulas, formatting, charting, cleaning messy data); create a new spreadsheet from scratch or from other data sources; or convert between tabular file formats. Trigger especially when the user references a spreadsheet file by name or path — even casually (like "the xlsx in my downloads") — and wants something done to it or produced from it. Also trigger for cleaning or restructuring messy tabular data files (malformed rows, misplaced headers, junk data) into proper spreadsheets. The deliverable must be a spreadsheet file. Do NOT trigger when the primary deliverable is a Word document, HTML report, standalone Python script, database pipeline, or Google Sheets API integration, even if tabular data is involved.

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Use this skill when conditioning, loading, preparing, or labeling signal data for analysis or ML training. Covers: cleaning a single signal (fill gaps, remove drift, deoutlier, denoise, resample/align a time base) BEFORE analysis; building a `signalDatastore` pipeline; creating a `labeledSignalSet` for Signal Labeler; deriving labels (filename, folder, in-file, ROI, time-frequency ROI); stratified train/val/test splits; framing long signals; parallel processing; and shaping datastore output for `trainnet`. Triggers include "clean up this signal", "remove drift / detrend", "fill gaps", "remove spikes / outliers", "denoise", "resample to a uniform rate", "align channels", "labels from filenames", "stratified split", "prepare for Signal Labeler", and function names like `fillgaps`, `fillmissing`, `detrend`, `filloutliers`, `smoothdata`, `resample`, `synchronize`, `signalDatastore`, `labeledSignalSet`, `filenames2labels`, `folders2labels`, `splitlabels`, `framesig`, `framelbl`, `createDatastores`.

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Run MATLAB test suites and analyze results, including test filtering, parallel execution, result diagnostics, code coverage collection, gap analysis, and CI/CD with buildtool. Use when running tests, filtering test suites, analyzing test failures, checking, collecting, or analyzing coverage, justifying uncovered code, or configuring CI pipelines. Do NOT use for writing, generating, or structuring tests. Do NOT use for Simulink coverage or Simulink testing workflows.

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Build machine vision inspection systems with MATLAB Visual Inspection Toolbox. Covers the full arc from problem selection through deployment: anomaly detection (Student-Teacher, PatchCore, FastFlow, FCDD), object detection (YOLOX), counting (CounTR, shape matching), gauging and measurement (caliper, fitcircle, fitangle), blob analysis (regionprops, calibrated measurement), shape matching for fixturing and localization, synthetic data generation for training augmentation, and deployment to standalone apps, embedded C/C++, NVIDIA GPUs (TensorRT), NPUs (ONNX), and Beckhoff PLCs. Routes to rule-based tools when problems are geometric and deterministic, AI-based tools when defect appearance varies, and hybrid pipelines combining both.

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Creates MATLAB interfaces to Python image processing and computer vision models from GitHub repositories or pip-installable packages using MPyReq. Use when asked to interface MATLAB with a Python CV/image model (segmentation, depth estimation, object detection, image generation, super-resolution, etc.), given a GitHub repo URL for an image/vision model, or asked to create an MPyReq demo for a deep-learning vision pipeline. Do NOT use for general-purpose Python-MATLAB interfacing, non-vision models (NLP, tabular, audio), model deployment/serving, or MATLAB-only image processing workflows.

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Build OCR pipelines in MATLAB using the ocr() function. Use this skill when the user wants to read text from images, documents, signs, meters, displays, license plates, gauges, receipts, or seven-segment displays. Covers image preprocessing, text detection (CRAFT, MSER), ROI-based recognition, multi-language OCR, and custom model training. Use when: OCR, text recognition, extract text from image, character recognition, document scanning, meter reading, gauge reading, receipt scanning, digitize text from photo.

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Perform static application security testing with tools like Semgrep, CodeQL, and SonarQube. Identify security vulnerabilities in source code before deployment. Use when implementing secure SDLC, code review automation, or security gates in CI/CD pipelines.

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Detect, respond to, and prevent software supply chain attacks on package registries, container images, and CI/CD pipelines with lockfile auditing, provenance verification, and emergency response playbooks.

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Build and operate Retrieval-Augmented Generation (RAG) infrastructure with vector stores, embedding pipelines, and hybrid search. Covers ingestion, chunking strategies, reranking, and production deployment patterns.

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