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Unsupervised clustering and cell-type identification for high-dimensional flow, spectral, and mass cytometry - FlowSOM, PhenoGraph, FlowSOM-via-CATALYST, with UMAP/tSNE for visualization. Covers the type-vs-state marker distinction (cluster on lineage, test state within clusters), over-provision-then-metacluster, the Weber-Robinson benchmark, seed dependence and metacluster stability, why embeddings are for looking not measuring, and median-heatmap annotation/merging. Use when discovering populations without predefined gates, choosing a clustering algorithm, selecting the number of metaclusters, or annotating clusters into cell types.

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Tests genotype-environment associations and identifies adaptive loci while correcting for the four-confound landscape (structure, demography, background selection, sampling design) using LFMM2 with mandatory K via sNMF cross-entropy elbow (LEA 3), BayPass Core/AUX/C2/IS with Omega covariance matrix, RDA / pRDA for polygenic adaptation (Forester 2018; requires imputed genotypes), OutFLANK with trimmed FST null, pcadapt, gradient forests (Ellis-Smith-Pitcher 2012, NOT mis-cited Ellis-Manel), Capblancq & Forester 2021 RDA Swiss-army-knife, genomic-offset prediction with Lind & Lotterhos 2025 three-regime caveat, Lotterhos-Whitlock sampling optima, Wang & Bradburd 2014 IBD vs IBE, and Circuitscape + ResistanceGA. Use when identifying adaptive loci across gradients, choosing K for LFMM2, deciding among GEA methods, predicting maladaptation with the novel-environment caveat, distinguishing IBD vs IBE, or optimizing sampling design.

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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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Query and download from NCBI Gene Expression Omnibus (GEO) and EMBL-EBI's BioStudies/ArrayExpress mirror. Use when finding expression datasets, navigating SuperSeries vs SubSeries, choosing between series-matrix (submitter-normalized) and raw supplementary files, downloading via GEOparse (Python) or GEOquery (R/Bioconductor), linking GEO to SRA for raw reads, or distinguishing GSE/GSM/GPL/GDS record types. Encodes the SuperSeries trap, the series-matrix normalization-trust caveat, GEOmetadb deprecation, ArrayExpress migration to BioStudies, and processed-vs-raw decision matrix.

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Build and analyze pangenomes for prokaryotes (Panaroo, PPanGGOLiN, PEPPAN, GET_HOMOLOGUES, anvi'o pangenomics) and eukaryotes (Minigraph-Cactus, PGGB, vg pangenome graphs). Implement Tettelin core/accessory/cloud genome decomposition (Tettelin 2005), Heap's law open/closed pangenome modeling, gene presence/absence GWAS (Scoary, pyseer), pangenome graph variant calling (vg, PanGenie), and structural-variation graph indexing. Use when assembling species- or genus-level pan-gene catalogs, separating core from accessory/shell/cloud genes, testing gene-content associations with phenotypes, building pangenome graphs from haplotype-resolved assemblies, calling SVs from pangenome graphs, or selecting between bacterial-pangenome and eukaryotic-pangenome workflows.

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Estimate bivariate genetic correlation (rg) between traits from GWAS summary statistics or individual-level genotypes using cross-trait LDSC, HDL, LAVA, rho-HESS, GREML-bivariate, Popcorn, and HDL-L. Use when quantifying shared genetic architecture between two traits, screening MR validity before causal inference, distinguishing global from locus-level rg, estimating trans-ancestry rg, separating partial from full causation via LCV gcp, or producing a STROBE-MR-compliant cross-trait sensitivity battery. Cross-trait LDSC intercept absorbs sample overlap and is NOT a bias; HDL is biased under sample overlap above ~5%. High rg between exposure and outcome motivates CHP-aware MR sensitivity (CAUSE, LHC-MR).

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Segments the genome into chromatin states from combinatorial histone modification and chromatin factor ChIP-seq data. Uses ChromHMM (multivariate HMM on binarized signal, v1.27), Segway (Dynamic Bayesian Network on continuous signal), EpiSegMix (flexible-distribution HMM with duration modeling, 2024), EpiLogos (multi-biosample visualization), IDEAS (cell-type-aware joint), and full-stack ChromHMM (Vu Ernst 2022) for cross-cell-type segmentations. Handles state-count selection (15 vs 18 vs 25 states), binarization choice, OverlapEnrichment / NeighborhoodEnrichment downstream analysis, and cross-biosample integration. Use when learning chromatin states from a histone mark panel, characterizing learned states by genomic feature enrichment, or comparing chromatin landscapes across cell types.

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Runs cis-pQTL Mendelian randomization for drug-target validation using UKB-PPP (Olink), deCODE (SomaScan), Fenland, INTERVAL, ARIC, and FinnGen-PPP proteomes plus colocalization triangulation, phenome-wide on-target adverse-effect scans, cross-platform Olink/SomaScan replication, and PAV (protein-altering variant) sensitivity. Use when nominating or de-risking a drug target from plasma-proteome GWAS, mimicking pharmacological inhibition via cis-pQTL instruments, separating shared-causal from LD-confounded signal under the Schmidt 2020 cis-MR framework, screening on-target adverse phenotypes pheWAS-style, or producing publication-grade STROBE-MR plus PP.H4 evidence for a target gene.

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Quantifies alternative splicing as PSI (percent spliced in) from RNA-seq using rMATS-turbo (BAM-based event), SUPPA2 (TPM-based event), MAJIQ V3 (LSV-based Bayesian), leafcutter (annotation-free intron clusters), VAST-TOOLS (cross-species with microexon support), Shiba (junction-imbalance-corrected, 2025 SOTA at low coverage), or IRFinder-S (intron retention coverage-aware). Distinguishes the five canonical event classes (SE, A5SS, A3SS, MXE, RI), special classes (microexons, exitrons, AFE/ALE), intron retention subtypes (canonical RI vs detained introns), and applies effective-length normalization. Use when measuring splice-site usage or isoform inclusion ratios from short-read RNA-seq.

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Use this skill when the user asks about workers compensation for trucking — required by state law, classification of drivers, premium calculation (rate × experience modifier × payroll), Common Claim types in trucking, returning injured drivers to work, claims management, premium reduction strategies, and the difference between WC and Occupational Accident insurance for owner-operators. Reference state WC laws + IFTA / fleet insurance.

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Use this skill when the user asks about trucking insurance — types of coverage (commercial auto, cargo, occupational accident, workers comp, bobtail/non-trucking, MCS-90 endorsement), federal minimums (49 CFR 387), what each covers, owner-operator vs company-driver implications, and how to read a Certificate of Insurance (COI). Cite 49 CFR 387.

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Use this skill to understand the 6 levels of FMCSA roadside inspections and what each covers. Helps drivers know what to expect and helps carriers respond to inspection types.

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Use this skill when the user asks about CMV operation types — Dedicated, OTR (Over-the-Road), Regional, Local, and the differences in driver lifestyle, pay, equipment, home time, hours, and customer mix. Reference industry segmentation conventions.

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Use this skill when the user asks about cargo securement requirements under 49 CFR 393 Subpart I — Working Load Limit (WLL), tiedown counts, tiedown types, commodity-specific securement rules (lumber, metal coils, paper rolls, concrete pipe, intermodal containers, vehicles, large boulders, dressed lumber, building materials), CVSA out-of-service criteria, and how to calculate aggregate WLL. Cite 49 CFR 393.100-136.

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Use this skill to understand why CSA BASIC alert thresholds differ across carrier types. Covers general freight (65th percentile), passenger/hazmat (60th), and the regulatory rationale.

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Use this skill when the user asks about FMCSA's Crash Preventability Determination Program (CPDP) — how to dispute that a crash was non-preventable, eligible crash types, evidence requirements, how preventability findings affect SMS scoring + safety ratings, the difference between "preventability" and "fault," and the National Crash Preventability Program. Cite FMCSA CPDP guidance.

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Adding a file type or upgrading any of its capability slots in the files feature (preview, edit, thumbnail, grid card, info, share, versions, conversion, diff, rail panel). Use when supporting a new extension or MIME type, building a previewer, touching FILE_TYPES, PreviewKind, FilePreview.tsx, EDITABLE_KINDS, or surfaces/single-file/, or working the FILE_SURFACES.md wishlist.

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Three.js textures - texture types, UV mapping, environment maps, texture settings. Use when working with images, UV coordinates, cubemaps, HDR environments, or texture optimization.

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Perform language and framework specific security best-practice reviews and suggest improvements. Use when the user explicitly requests security best practices guidance, a security review/report, or secure-by-default coding help. Trigger only for supported languages (python, javascript/typescript, go), and not for general debugging or non-security tasks.

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Three.js lighting - light types, shadows, environment lighting. Use when adding lights, configuring shadows, setting up IBL, or optimizing lighting performance.

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Guide for creating high-quality MCP (Model Context Protocol) servers that enable LLMs to interact with external services through well-designed tools. Use when building MCP servers to integrate external APIs or services, whether in Python (FastMCP) or Node/TypeScript (MCP SDK).

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Configure a Node.js project with pnpm, TypeScript, latest versions, and parallel script patterns following modern best practices

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Improves typography by fixing font choices, hierarchy, sizing, weight, and readability so text feels intentional. Use when the user mentions fonts, type, readability, text hierarchy, sizing looks off, or wants more polished, intentional typography.

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Guide for when to use and when not to use return validators in Convex functions. Use this skill whenever the user is writing Convex queries, mutations, or actions and needs guidance on return value validation. Also trigger when the user asks about Convex type safety, runtime validation, AI-generated Convex code, Convex AI rules, Convex security best practices, or when they're debugging return type issues in Convex functions. Trigger this skill when users mention "validators", "returns", "return type", or "exact types" in the context of Convex development. Also trigger when writing or reviewing Convex AI rules or prompts that instruct LLMs how to write Convex code.

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