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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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Normalize read-depth copy-ratio profiles and segment them into copy-number regions using circular binary segmentation (CBS, DNAcopy), hidden Markov models, HaarSeg, and fused-lasso methods. Covers GC-content, mappability, and replication-timing (wave-artifact) bias correction, panel-of-normals/PCA denoising, diploid-baseline centering, and algorithm selection by sequencing depth and event size. Use when choosing a segmentation algorithm, correcting depth bias, diagnosing oversegmentation or a mis-centered baseline, tuning CBS or HMM parameters, or understanding why a downstream CNV caller produced fragmented or shifted segments.

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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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Visualize copy number profiles, segments, allele-specific tracks, and cohort patterns from CNVkit, GATK, ASCAT, FACETS, Sequenza, and other callers. Covers genome-wide and per-chromosome log2 scatter plots, B-allele-frequency/minor-allele-fraction tracks, ideograms, cohort heatmaps, circos views, and caller-native plots. Use when creating publication CNV figures, choosing which plot answers a given question, diagnosing a wrong diploid baseline visually, displaying loss of heterozygosity, or deciding what depth-only plots cannot reveal.

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Calculates molecular fingerprints (ECFP/Morgan, FCFP, MACCS, RDKit, AtomPair, TopologicalTorsion, Avalon, MAP4, MHFP6) and physicochemical descriptors (Lipinski, QED, TPSA, Crippen LogP, 3D shape) with explicit choice tables, bit vs count semantics, and partial-charge model selection. Use when featurizing molecules for similarity, QSAR, virtual screening, or ML, or selecting the correct fingerprint for a chemotype-aware task.

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Searches molecular libraries for substructure matches using SMARTS patterns with explicit handling of recursive SMARTS, ring membership, aromaticity dialect, vector binding, atom map indices, and reactive/PAINS/REOS/Brenk/Aldridge filter catalogs. Use when filtering compounds by pharmacophore features, functional groups, scaffold matches, or screening for assay-interference / structural alerts.

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Estimate SNP heritability and partition 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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Enumerates virtual chemical libraries via reaction SMARTS transformations using RDKit and Reaction templates, with explicit handling of atom mapping, template extraction (RDKit reaction mining), product validation, RECAP/BRICS fragmentation, R-group decomposition, matched molecular pair analysis (MMPA), and Free-Wilson analysis. Use when generating combinatorial libraries from building blocks, enumerating analog series, deriving structure-activity rules, or extracting transformations from reaction data.

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Map nucleosome center positions, occupancy, and fuzziness from ATAC-seq fragment-size patterns using NucleoATAC, ATACseqQC, DANPOS3, or scprinter. Use when characterizing nucleosome organization at promoters and enhancers, calling +1/-1 nucleosomes flanking NFRs, generating V-plots for chromatin structure visualization, or comparing nucleosome positioning between conditions.

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Filter alignments by flags, mapping quality, and regions using samtools view and pysam. Use when extracting specific reads, removing low-quality alignments, or subsetting to target regions.

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Creates sashimi-style plots showing RNA-seq read coverage and splice junction counts using ggsashimi (general-purpose, condition-grouped overlays), rmats2sashimiplot (rMATS-output-aware), MAJIQ-VOILA (LSV posteriors interactive HTML), leafviz (leafcutter clusters Shiny), Jutils (tool-agnostic heatmaps and sashimi for rMATS/leafcutter/SUPPA2/MAJIQ output), or pyGenomeTracks (multi-track publication figures). Tool choice depends on the upstream differential-splicing tool's output format and the publication vs interactive use case. Use when visualizing specific splicing events, validating differential splicing calls, or producing publication-quality figures.

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Analyzes alternative splicing from PacBio Iso-Seq (HiFi, Kinnex/MAS-Iso-seq) and Oxford Nanopore (direct cDNA, direct RNA, R10.4.1+) long-read RNA-seq with full-isoform resolution. Tools include FLAIR (correct/collapse/quantify/diffSplice for PacBio + ONT), IsoQuant (de-novo or annotation-guided isoform discovery 2024 SOTA), Bambu (annotation-aware Bayesian discovery + quantification with Novel Discovery Rate), SQANTI3/SQANTI-LR (isoform classification: FSM/ISM/NIC/NNC + artifact flags), rMATS-long (event calling on long-read isoforms), and minimap2 (-ax splice:hq for HiFi; -ax splice -k14 for ONT cDNA; add -uf only for direct RNA or stranded cDNA preps). Solves microexon detection, recursive splicing, complex multi-exon isoforms, and DTU without transcript-quantification uncertainty. Use when short-read AS limitations (anchor length, complex isoforms, microexons, recursive splicing, transcript ambiguity) demand full-isoform resolution.

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Google SEO APIs: Search Console (Search Analytics, URL Inspection, Sitemaps), PageSpeed Insights v5, CrUX field data with 25-week history, Indexing API v3, and GA4 organic traffic. Provides real Google field data for Core Web Vitals, indexation status, search performance, and organic traffic trends. Use when user says "search console", "GSC", "PageSpeed", "CrUX", "field data", "indexing API", "GA4 organic", "URL inspection", or "real CWV data".

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Local SEO analysis covering Google Business Profile optimization, NAP consistency, citation health, review signals, local schema markup, location page quality, multi-location SEO, and industry-specific recommendations. Detects business type (brick-and-mortar, SAB, hybrid) and industry vertical. Use when user says "local SEO", "Google Business Profile", "GBP", "map pack", "local pack", "citations", "NAP consistency", "service area", or "multi-location".

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Pipeline that turns a big system idea into briefs for an agent fleet. Use when Arman says 'let's plan out X', 'build or overhaul the X system', 'create the vision and plan for X', 'do the full discovery process', 'get this ready for a fleet', or 'do what we did for education', or when carrying forward a VISION, COMPETITIVE_INSIGHTS, roadmap, or briefs doc. NOT for one feature in a live system (use build-sub-feature).

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Sets up Convex auth, identity mapping, and access control. Use for login, auth providers, users tables, protected functions, or roles in a Convex app.

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Set up Convex authentication with proper user management, identity mapping, and access control patterns. Use when implementing auth flows, setting up OAuth providers, or adding role-based access control.

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PSR-4 autoloading standard knowledge base for PHP 8.5 projects. Provides quick reference for namespace-to-path mapping, composer.json configuration, directory structure, and common mistakes. Use for autoloading audits and project structure reviews.

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Generates Bulkhead pattern for PHP 8.5. Creates resource isolation with semaphore-based concurrency limiting and thread pool isolation. Includes unit tests.

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[40] PLAN. Create clear action plans with steps, success criteria, and risk awareness. Use before implementing features, making changes, starting projects, or anytime you need a roadmap to success. Triggers on "plan this", "how should we approach", "what's the strategy", "steps to complete", or when facing complex multi-step work.

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[30] ANALYZE. Understand how changes impact the system — what's the core, what's affected, what depends on what. Use when planning changes, analyzing systems, debugging issues, or anytime you need to see the full picture of cause and effect. Triggers on "what's affected", "impact analysis", "dependencies", "scope mapping", or when you need to understand ripple effects.

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3D web graphics with Three.js (WebGL/WebGPU). Capabilities: scenes, cameras, geometries, materials, lights, animations, model loading (GLTF/FBX), PBR materials, shadows, post-processing (bloom, SSAO, SSR), custom shaders, instancing, LOD, physics, VR/XR. Actions: create, build, animate, render 3D scenes/models. Keywords: Three.js, WebGL, WebGPU, 3D graphics, scene, camera, geometry, material, light, animation, GLTF, FBX, OrbitControls, PBR, shadow mapping, post-processing, bloom, SSAO, shader, instancing, LOD, WebXR, VR, AR, product configurator, data visualization, architectural walkthrough, interactive 3D, canvas. Use when: creating 3D visualizations, building WebGL/WebGPU apps, loading 3D models, adding animations, implementing VR/XR, creating interactive graphics, building product configurators.

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2D game development principles. Sprites, tilemaps, physics, camera.

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[21] UNDERSTAND. Deep research workflow for this project using 150% scope (100% core + 50% boundary), evidence-based reasoning, and structured investigation notes. Use when the task requires investigation, root-cause analysis, or mapping unknown areas. Always maintain a research log file that captures findings, hypotheses, and next branches; use web.run when external verification is needed.

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