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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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Produce and interpret PCA, t-SNE, UMAP, and PHATE plots for high-dimensional omics data with rigor about which method preserves what (variance, local structure, manifold, transitions), hyperparameter sensitivity, and the well-documented limits of 2D embeddings. Covers PCA biplot/scree/loadings, t-SNE PCA initialization (Kobak-Berens 2019), UMAP n_neighbors/min_dist trade-offs, and the Chari-Pachter 2023 critique. Use when visualizing high-dimensional data — bulk PCA, single-cell embeddings, multi-omics integration projections.

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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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Handles batch effects in bulk RNA-seq via design-matrix inclusion (the correct path for DE), ComBat/ComBat-seq for visualization, SVA for unknown latent factors, RUVSeq for negative-control-gene-anchored unwanted variation, and limma::removeBatchEffect for plotting only. Encodes the Nygaard 2016 cardinal sin against testing on a batch-corrected matrix, the choice between SVA/RUVg/RUVs/RUVr, the confounding non-identifiability problem, the single-cell boundary (Harmony/MNN are NOT for bulk), and the Goh 2017 harmonization critique. Use when designing a DE analysis with batch structure, troubleshooting batch-dominated PCA, choosing ComBat vs ComBat-seq, handling unknown batch via SVA, integrating across studies, or deciding when (rarely) to subtract batch.

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Build publication-quality figures with matplotlib using the object-oriented Figure/Axes API, constrained_layout, rcParams customization, TrueType (Type-42) font embedding for journal submission, and CVD-safe palettes. Covers seaborn integration, common chart types, axis formatting, and the small gotchas that distinguish reproducible matplotlib from notebook scratch. Use when producing publication figures in Python — RNA-seq scatter, single-cell embeddings, generic biological plotting.

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Plot per-gene mutation distributions on a protein-domain map (lollipop / needle plots) showing mutation position, recurrence count, and variant classification with maftools, g3-lollipop, trackViewer, and ProteinPaint. Use when visualizing recurrent mutation hotspots on a single gene's protein, marking domain boundaries from UniProt/Pfam, comparing missense vs truncating distributions, or contrasting two cohorts on the same lollipop.

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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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Infer orthologous genes and gene families across species using OrthoFinder3 (HOG-based phylogenetic orthology), SonicParanoid2, Broccoli, ProteinOrtho, OMA / FastOMA hierarchical orthologous groups, eggNOG-mapper, JustOrthologs, and TOGA whole-genome-alignment orthology. Use when building single-copy ortholog sets for phylogenomics, classifying co-orthologs and in/out-paralogs after gene duplication, propagating functional annotation via orthology with awareness of the ortholog conjecture, distinguishing speciation from duplication via gene-tree species-tree reconciliation, computing Quest-for-Orthologs benchmark performance, or running synteny-aware ortholog detection in WGD-affected lineages.

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Preprocess CLIP-seq reads (eCLIP, iCLIP, iCLIP2, iCLIP3, irCLIP, PAR-CLIP, FLASH) with protocol-specific UMI extraction, adapter trimming, length filtering, and post-alignment PCR-duplicate collapse. Use when raw CLIP FASTQ must be turned into deduplicated, crosslink-preserving BAM input for peak calling; choosing between two-pass and single-pass adapter trimming; deciding minimum read length; or mapping UMI patterns to specific eCLIP/iCLIP/iCLIP2/iCLIP3 library preps.

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Map N6-methyladenosine (m6A) RNA modifications at single-nucleotide resolution using miCLIP (Linder 2015), miCLIP2 + m6Aboost machine learning (Kortel 2021), GLORI (Liu 2023, antibody-free chemical conversion), DART-seq (Meyer 2019, APOBEC1-YTH fusion), m6Anet (nanopore direct RNA), or MeRIP-seq with calibration. Use when distinguishing antibody-based from antibody-free m6A detection methods, applying the DRACH motif constraint, reconciling cross-method disagreements (DART 44% in DRACH vs GLORI), or detecting m6Am at the cap.

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Discover RBP binding motifs from CLIP-seq peaks or single-nucleotide crosslink sites using HOMER, MEME/STREME, kpLogo, mCross (CL-position-registered motifs), PEKA (positional k-mer enrichment), RBPamp (affinity), and RNA Bind-n-Seq (RBNS) cross-validation. Use when characterizing RBP sequence specificity, registering motifs to crosslink positions, validating in vivo CLIP motifs against in vitro RBNS Kd, reconciling motif disagreements across tools, or correcting for the uracil crosslinking bias that contaminates raw CLIP motif logos.

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Generates 3D conformer ensembles using RDKit ETKDGv3 with knowledge-enhanced distance geometry, MMFF94/UFF force-field optimization, CREST + GFN2-xTB semi-empirical refinement, and macrocycle-aware torsion preferences. Provides explicit decision rules for single vs ensemble conformer use, RMSD pruning, energy windows, conformer count, and force-field choice. Use when preparing 3D ligands for docking, generating descriptor input for 3D QSAR, or sampling macrocycle/peptide conformational ensembles.

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Test whether two or more traits share a causal variant at a locus using Bayesian colocalization (coloc.abf, coloc.susie, HyPrColoc, moloc, eCAVIAR, SMR/HEIDI, PWCoCo, SharePro). Use when integrating GWAS with eQTL/sQTL/pQTL/mQTL, distinguishing shared causal variants from LD-driven coincidence, handling allelic heterogeneity, choosing between single-causal vs multi-causal methods, picking PP.H4 thresholds, running sensitivity over p12, or harmonising summary statistics for colocalization.

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Analyze TF motif accessibility variability across samples or single cells using chromVAR. Use when identifying TF motifs whose accessibility correlates with conditions, computing per-sample motif z-scores after matched background correction, comparing to ArchR / Signac equivalents, or distinguishing motif-accessibility signal from per-site footprinting.

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Installs 425 bioinformatics skills covering sequence analysis, RNA-seq, single-cell, variant calling, metagenomics, structural biology, and 56 more categories. Use when setting up bioinformatics capabilities or when a bioinformatics task requires specialized skills not yet installed.

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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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Use when the user wants to triage a CORPUS of production crashes/hangs from an aggregator (Sentry, App Store Connect) — grouped, counted issues — rather than a single crash file.

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Generate a high-quality deep-reading note for a single paper and write it into an Obsidian-style vault. Use when the user gives a paper title, DOI, URL, arXiv ID, Zotero item, or local PDF and wants a polished Markdown note with strong structure, evidence-based analysis, and figure placeholders.

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Postgres best practices maintained by Supabase, for Postgres running anywhere. Load this skill BEFORE writing or changing anything that lives in a Postgres database: creating or altering tables and columns (including choosing column types), schema design, migrations and declarative schema files, RLS policies and the tests that verify them, indexes, triggers, database functions, queues and scheduled jobs (pg_cron, pgmq), vector/semantic search (pgvector), and restoring dumps (pg_restore) or importing data. Also load it when diagnosing slow queries, high CPU, timeouts, EXPLAIN plans, connection exhaustion, locking, bloat, or rows visible to the wrong user or tenant. This is not just a performance guide — schema, migration, security, and SQL authoring tasks need these rules too, even for a one-column change or a single query.

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Guides Metronome usage-based billing integration decisions — event ingestion (single and batch, idempotency, billable metrics), contract design (rate cards, overrides, dimensional pricing, products), invoicing lifecycle (grace periods, finalization, Stripe sync), credit and commit management (prepaid, postpaid, thresholds, auto-recharge), and Stripe integration (arrears invoicing, tax providers, line item limits). Use when building, modifying, or reviewing any Metronome integration — including ingesting usage events, creating customers, contracts, or rate cards, designing billable metric group keys, managing credits and commits, configuring invoicing, syncing invoices with Stripe Billing, billing AI applications for token usage, setting up self-serve (PLG) pricing, reviewing customer health, commit burn, portfolios, or renewals, or migrating from Stripe Billing Meters to Metronome.

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Generate standard-compliant IEEE 802.11 waveforms using MATLAB WLAN Toolbox. Use when creating WLAN waveforms, PPDU packets, or the transmit side of a link-level simulation. Covers all formats: Non-HT (802.11a/g), HT (802.11n), VHT (802.11ac), HE-SU/HE-MU/HE-TB (802.11ax), EHT-MU/EHT-TB (802.11be), UHR-MU/UHR-TB/UHR-ELR (802.11bn). Handles single-user, MU-MIMO, OFDMA, trigger-based uplink, extended range, preamble puncturing, UEQM, and DRU. Use when asked to generate test waveforms, create packets with MAC frames, configure OFDMA resource units, build trigger-based uplink transmissions, target a specific transmit duration, or build multi-packet waveforms.

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Via modeling: pads, antipads, ground return vias, GRV placement, and signal integrity for high-speed layer transitions. TRIGGER: user asks to model a via, design a via transition, place ground return vias, analyze via performance, or check signal integrity through layer transitions. Invoke BEFORE writing code — only viaSingleEnded exists (no viaDifferential), and the location format is non-obvious. SKIP: general signal integrity without vias (use matlab-analyze-em), transmission line design (use matlab-design-pcb-transmission-line), PDN analysis (use matlab-analyze-pcb-pdn), material/stackup setup only (use matlab-manage-pcb-material).

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Cascade PCB components, add lumped elements, export Touchstone, and bridge to eye diagram or antenna array workflows. TRIGGER: user asks to cascade or connect multiple RF PCB components, add lumped R/L/C, export S-parameters to Touchstone, or combine PCB elements into a circuit. Invoke BEFORE writing pcbcascade or circuit code — cascade rules and port matching are non-obvious. SKIP: designing individual components (use the specific matlab-design-pcb-* skill), EM analysis of a single component (use matlab-analyze-em), material/stackup setup only (use matlab-manage-pcb-material), optimization (use matlab-optimize-pcb-design).

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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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