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Identifies non-coding RNAs (tRNA, rRNA, snoRNA, snRNA, riboswitches, sRNAs) using Infernal covariance-model search against Rfam, tRNAscan-SE 2.0 for tRNA, barrnap for rRNA, and ARAGORN for tmRNA, plus the small-RNA-seq boundary for miRNA and the transcript-assembly boundary for lncRNA. Covers the structure-conserved-not-sequence-conserved principle (why BLAST fails), GA-threshold and clan-competition correctness, tRNAscan-SE domain modes and pseudogene flags, rDNA copy-number collapse, and why homology annotation is a recall floor. Use when performing genome-wide ncRNA annotation, choosing the right tool for an RNA class, or interpreting ncRNA counts.

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Assigns pathogen lineages (SARS-CoV-2 Pangolin UShER mode; Nextclade clade + QC; pango-designation alias resolution) and tracks variant frequencies over time using Nextstrain (Augur + Auspice), wastewater deconvolution (Freyja, COJAC, alcov, lineagespot), lineage-fitness modelling (multinomial logistic), and recombinant detection (3SEQ, RDP4, Bolotie). Covers Pangolin pangolin-data and Nextclade dataset version pinning (mandatory; lineage-defining mutations change with dataset), Freyja barcode forward-only date constraint, ARTIC primer scheme churn (V3/V4/V4.1/V5.3.2/Midnight) with dropout regions, and recombinant X-prefix designation lag. Use when assigning Pango lineages and Nextclade clades to viral consensus sequences, building Nextstrain Augur surveillance pipelines, deconvolving wastewater into lineage frequencies with Freyja, tracking lineage frequencies over time, handling ARTIC primer dropouts, or running surveillance for SARS-CoV-2/influenza/Mpox/RSV/H5N1/measles.

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Analyzes species-environment relationships with constrained ordination (CCA, RDA, db-RDA), variance partitioning, indicator species (indicspecies IndVal.g group-equalized), PERMANOVA paired MANDATORILY with PERMDISP (Anderson & Walsh 2013; dispersion confounds centroid tests), Joint Species Distribution Models (HMSC, sjSDM, gjam) with explicit rejection of "residual covariance equals biotic interaction", phylogenetic community ecology (SES_MPD/MNTD), trait-environment via RLQ + fourth-corner with corrected modeltype=6 (Dray 2014), bipartite network metrics (NODF, modularity) with curveball null (Strona 2014), and Mantel-test replacements (dbRDA, GDM) for spatial data. Use when testing how environmental gradients structure communities, identifying habitat indicator taxa, partitioning variance among predictors, deciding whether PERMANOVA significance is location vs dispersion, picking among HMSC/sjSDM/gjam, or replacing Mantel tests for landscape data.

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Quantifies biodiversity from species abundance/incidence tables using Hill numbers (iNEXT) with coverage-based rarefaction-extrapolation (Chao & Jost 2012), asymptotic richness via Chao1/ACE/jackknife as a lower bound, Baselga turnover/nestedness partition with the Podani alternative as sensitivity check, mandatory Hellinger transformation before ordination (Legendre & Gallagher 2001), Faith PD and SES_MPD/SES_MNTD with explicit null-model choice, and Maire 2015 functional-diversity dimensionality optimization. Use when comparing diversity across sites with unequal sampling effort, picking the right richness estimator for singleton-heavy amplicon data, partitioning beta diversity into turnover vs nestedness, reporting Hill-number effective species counts rather than raw entropies, computing SES_MPD with explicit null-model justification, or deciding whether to apply standard metrics to compositional amplicon data. Not for clinical 16S microbiome diversity (see microbiome/diversity-analysis).

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Batch effect correction for CRISPR screens covering ComBat empirical-Bayes, RUV, SVA, control-sgRNA normalization, and the model-based alternative of including batch as a covariate in MAGeCK MLE or Chronos. Covers screen-specific batch sources (passage cohort, library lot, infection day, sequencing run, Cas9 lot, FBS lot), PCA + variance-decomposition diagnostic to decide if correction is needed, when correction harms biology by over-correcting condition into batch, limma removeBatchEffect for visualization-only correction, and relationship to multi-condition design matrices. Use when combining screens for joint analysis, when passage cohort confounds biology, when DepMap-style panels need Chronos with batch covariates, when picking ComBat vs RUV, or when correction harms biology and should be replaced with explicit covariate modeling.

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Cross-method decision tree for calling hits in pooled CRISPR screens. Catalogs statistical models (MAGeCK RRA, MAGeCK MLE, BAGEL2, drugZ, JACKS, Chronos, CERES), experimental designs each is built for, failure modes outside design domain, reconciliation when methods disagree, multiple-testing and effect-size thresholds, the order of operations (count -> QC -> CN-correct -> hit-call -> validate), the second-best-sgRNA conservative rule, and consensus-hit strategy. Use when choosing among MAGeCK / BAGEL2 / drugZ / JACKS / Chronos for a given design, reconciling disagreement across two or three methods on the same screen, deciding whether to require consensus, gating downstream validation by hit-confidence tier, or interpreting unstable hit lists across reruns.

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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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Reconcile gene trees against a species tree under probabilistic models of duplication, transfer, and loss (DTL) using ALE (Szöllősi 2013 amalgamated likelihood), GeneRax (Morel 2020 ML reconciliation), AleRax (Morel 2024 co-estimation), Whale.jl (Bayesian DL+WGD), RANGER-DTL 2 parsimony, NOTUNG, ecceTERA, and Treerecs. Use when inferring ancestral gene-family content, distinguishing duplication from horizontal transfer from differential loss, rooting deep species trees from gene-content signals (STRIDE / Williams 2017 ALE-rooting), counting DTL events per branch, refining noisy gene trees against a species tree, modeling WGD events jointly with DTL, or producing publication-grade gene-family histories for phylogenomic / comparative analyses.

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Model gene-family birth-death dynamics across a species tree using CAFE5 (Mendes et al 2020 Bioinformatics 36:5516 gamma-distributed rate categories), CAFE5-error (annotation-error-aware), Count (Csurös 2010 ancestral state reconstruction), BadiRate (Librado 2012 likelihood + parsimony), DupliPHY-Family, and ALE/AleRax (for per-family DTL; see [[gene-tree-species-tree-reconciliation]]). Test lineage-specific gene-family expansions and contractions, distinguish biological dynamics from annotation artifacts, account for assembly fragmentation, identify functional enrichment in expanded / contracted families. Use when correlating gene-family changes with phenotype evolution, ranking lineages by adaptive gene-family-rate shifts, post-WGD dosage-balance analysis, or building Birth-death models from OrthoFinder presence/absence matrices.

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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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Call copy number variants with the GATK best-practices workflows — the somatic CNV pipeline (CollectReadCounts, DenoiseReadCounts with tangent normalization, ModelSegments, CallCopyRatioSegments) and the germline GATK-gCNV pipeline (DetermineGermlineContigPloidy, GermlineCNVCaller cohort/case mode, PostprocessGermlineCNVCalls). Covers panel-of-normals construction, AnnotateIntervals/FilterIntervals, allelic-count integration, and QS-based filtering. Use when integrating CNV calling into a GATK variant pipeline, calling rare germline CNVs from an exome cohort, deciding between the somatic and germline GATK workflows, or diagnosing why tangent normalization removed a real event or why gCNV output has low precision.

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Builds and applies 3D pharmacophore models using RDKit Pharm3D, the apo2ph4 receptor-based workflow (Heider et al. 2023), Pharmer / Pharmit for search, and PharmacoForge for protein-pocket-conditioned pharmacophore generation (Flynn et al. 2025), covering ligand-based pharmacophores from active-set alignment and receptor-based pharmacophores from binding-pocket geometry. Explicitly handles feature types, geometric tolerances, partial matching, and pharmacophore-based virtual screening. Use when identifying scaffold-hopping candidates, building shape-and-feature search queries, or transferring SAR across chemotypes.

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Sequence-based deep learning for ATAC-seq using chromBPNet, BPNet, scBasset, or Enformer. Use when correcting Tn5 bias with neural networks beyond k-mer models, predicting per-base accessibility profiles, scoring in silico variant effects at GWAS or rare-variant SNPs, discovering motifs via DeepLIFT/TF-MoDISco from a trained model, or generating cell-type-specific accessibility predictions for unobserved cell states.

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Estimates SNP heritability and partitions it across functional annotations, cell types, and loci from GWAS summary statistics or individual-level genotypes. Implements LDSC, stratified LDSC with the baseline-LD model, Finucane 2018 cell-type prioritization, LDAK SumHer, HDL, HESS local heritability, BOLT-REML, GCTA-GREML, graphREML, and Popcorn cross-population genetic correlation. Use when computing total h2_SNP from summary stats, partitioning heritability across functional categories, prioritizing trait-relevant tissues or cell types from ENCODE/Roadmap chromatin marks, reconciling LDSC vs LDAK enrichment estimates, computing local heritability with HESS, estimating genetic correlation between traits, or producing publication-grade enrichment with calibrated sensitivity to model assumptions.

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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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Implement, review, or improve CloudKit and iCloud sync in iOS/macOS apps. Use when working with CKContainer, CKRecord, CKQuery, CKSubscription, CKSyncEngine, CKShare, NSUbiquitousKeyValueStore, or iCloud Drive file coordination; when syncing SwiftData models via ModelConfiguration with cloudKitDatabase; when handling CKError codes for conflict resolution, network failures, or quota limits; or when checking iCloud account status before performing sync operations.

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This skill should be used when user asks to "improve my mAP", "why is my model overfitting", "my training is diverging", "read my results.csv", "interpret my training curves", "my AP50 is good but AP50-95 is bad", "my recall is low", "how do I pick learning rate", "which augmentations should I use", "should I use a bigger model", "tune hyperparameters", or asks how to train YOLO26 for detection, instance or semantic segmentation, pose, OBB, classification, or depth.

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MongoDB schema design patterns and anti-patterns. Use when designing data models, reviewing schemas, migrating from SQL, or troubleshooting performance issues caused by schema problems. Triggers on "design schema", "embed vs reference", "MongoDB data model", "schema review", "unbounded arrays", "one-to-many", "tree structure", "16MB limit", "schema validation", "JSON Schema", "time series", "schema migration", "polymorphic", "TTL", "data lifecycle", "archive", "index explosion", "unnecessary indexes", "approximation pattern", "document versioning".

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RF Toolbox and RF Blockset in MATLAB -- S-parameter I/O, network conversions (S/Z/Y/ABCD/T/H/G, mixed-mode), cascade/de-embedding, rfbudget analysis, circuit composition, matching networks, amplifier stability, mixer spurs, rational fitting, SI channels, baseband processing, Circuit Envelope simulation. Trigger: sparameters, Touchstone, .s2p, .s4p, rfplot, smithplot, rfparam, rfwrite, zparameters, yparameters, abcdparameters, s2sdd, cascadesparams, deembedsparams, rfbudget, noise figure, OIP3, IIP3, amplifier, modulator, nport, rffilter, attenuator, seriesRLC, shuntRLC, lcladder, txline, circuit, setports, clone, matchingnetwork, stabilityk, stabilitymu, powergain, gammams, gammaml, mixerIMT, OpenIF, rational, rationalfit, stepresp, txlineWRLGC, rf.Amplifier, rf.Mixer, rf.Filter, rf.Sparameter, rfsystem, RF Blockset.

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Modernize removed or discouraged MATLAB functions and patterns. Use when the check_matlab_code MCP tool reports that a function "is not recommended", "will be removed in a future release", or "has been removed" — at any severity (info, warning, or error) — when migrating legacy code, or when replacing removed or discouraged APIs with current equivalents. Also applies to discouraged patterns Code Analyzer does not flag (containers.Map, bsxfun, str2num, eval, clear all) and to removed or discouraged functions such as trainNetwork, csvread, xlsread, datenum, guide, svmtrain, ltln2val, webmap.

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Unified skill for all MATLAB and Simulink report generation tasks. Covers report generation, PDF report, document generation, mlreportgen, Report Generator, template, TitlePage, Chapter, multipage HTML, HTMLPage, html-multipage, custom reporter, customizeReporter, template hole, page header, page border, company style package, branded reporters, buildTemplates, Simulink report, model documentation, slreportgen, block diagram report, model report, subsystem documentation, SystemDiagramFinder, SystemIO, ExecutionOrder, LookupTable, template style, page footer, TemplateSrc, report package, table variants, multiple HTML pages, PDF report generation, Word report, DOM API, FormalTable, BaseTable, Figure, FormalImage, Section.

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Use this skill to classify tabular data end-to-end in MATLAB — load a dataset, prepare and clean it, select promising classifiers, train them, and compare accuracies with cross-validation, holdout, or hyperparameter optimization plus statistical tests. TRIGGER when: user asks to classify tabular data, pick classifiers for a dataset, compare classifier accuracy, run cross-validation or a holdout evaluation, or find the best model with statistical uncertainty. DO NOT TRIGGER when: user has non-tabular inputs (images, sequences, time series), wants a regression model, is training a specific neural network architecture (use matlab-train-network), or wants cost-sensitive learning or an arbitrary class-prior vector (this skill only supports the built-in uniform-prior toggle for imbalanced data).

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Fit SimBiology model parameters to data — fitproblem, population NLME, virtual patients, and NCA. Use when asked to fit, estimate, calibrate, or compute PK metrics.

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Simulate SimBiology models — ODE, stochastic (SSA), scenarios, and sensitivity analysis. Use when asked to run, simulate, predict, explore what-if, or identify influential parameters.

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