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Generates, normalizes, and converts bedGraph signal tracks (4-column chrom/start/end/value, 0-based half-open) with bedtools genomecov, deepTools bamCoverage/bamCompare/bigwigCompare, bedtools unionbedg, and UCSC bedGraphToBigWig. Covers why a raw coverage bedGraph is not comparable across samples until normalized, the CPM/RPKM/BPM/RPGC normalization menu and the conserved-total assumption that makes them wrong under a global perturbation, the strict sorted-non-overlapping-chrom.sizes bedGraphToBigWig contract that silently corrupts a bigWig, effective-genome-size selection, and bin-size aliasing. Use when building or normalizing a coverage/signal track from a BAM, comparing tracks across samples or conditions, converting bedGraph to a browser-ready bigWig, or diagnosing a track that looks plausible but reports wrong heights.

日本語の概要は準備中です。原文の説明を表示しています。

Detects focal chromatin loops (point interactions / corner-dots) in balanced Hi-C and Micro-C contact maps and aggregates/validates a loop set. Covers de-novo calling with cooltools dots (HiCCUPS-style 4-background local enrichment with lambda-chunked FDR), chromosight (template-correlation), and Mustache (scale-space blob detection); aggregate peak analysis (APA) via cooltools pileup for confirmation; the depth/resolution prerequisite (de-novo needs ~5-10kb resolution = hundreds of millions to billions of valid pairs); consensus across callers and convergent-CTCF support as validation; and differential loops via union anchors plus chromosight quantify. Use when calling chromatin loops or dots from a cooler, deciding whether a map is deep enough to call de-novo vs running APA on known CTCF/cohesin anchors, building an aggregate peak pileup, comparing loops across conditions, or validating loop calls. For HiChIP/PLAC-seq/PCHi-C protein-anchored data use FitHiChIP/MAPS, not dots.

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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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Bead-based signal normalization and cross-batch harmonization for CyTOF and high-parameter cytometry - EQ four-element bead normalization of instrument sensitivity drift (CATALYST normCytof, premessa), and reference-anchor cross-batch normalization (CytoNorm, per-cluster quantile splines). Covers the distinction between within-run drift correction and between-batch correction, the mandatory anchor/reference sample, why normalization is per-cluster with many quantiles, and the over-correction risk. Use when correcting CyTOF signal drift, harmonizing multi-batch or multi-site studies, or deciding whether to normalize data versus model batch in the design.

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Runs JACKS (Joint Analysis of CRISPR/Cas9 Knockout Screens; Allen et al 2019 Genome Research) which models per-sgRNA log-fold-change as the product of a treatment-dependent gene-essentiality term and a treatment-independent guide-efficacy term. Covers the Bayesian decomposition math, the hierarchical efficacy prior shared across screens performed with the same library, when JACKS outperforms MAGeCK (multi-screen joint analysis, libraries with broad efficacy variance) and when it does not (single screen, novel libraries with no prior efficacy), library-reuse efficacy transfer, downstream essentiality interpretation, and the 2.5x sample-size reduction enabled by efficacy-aware testing. Use when running multiple screens with the same library, when guide-level noise is suspected to dominate per-gene signal, when reusing published essentiality reference screens for efficacy priors, or when comparing screens performed across cell lines that share library but differ biologically.

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Bulk-query Ensembl BioMart (and other BioMart instances) for cross-database ID mapping, gene/transcript/exon coordinates, and ortholog tables. Use when batch-converting Ensembl IDs to other namespaces (HGNC, RefSeq, UniProt, Entrez), pulling gene coordinate tables for thousands of genes, building ortholog wide-tables across species, or replacing slow Ensembl REST loops with one-shot bulk export. Encodes BioMart's XML query format, R biomaRt vs Python pybiomart trade-off, mart-vs-dataset hierarchy, and the URL endpoint that's BioMart-specific (separate from rest.ensembl.org).

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Annotate CLIP-seq peaks or crosslink sites to RNA features (5'UTR, CDS, 3'UTR, intron, splice junction, snoRNA, tRNA, ncRNA, repeat elements) with ChIPseeker, RCAS, RBP-Maps (Yeo splicing regulatory maps), and bedtools, applying feature-priority hierarchies, transcript-context resolution, and metagene aggregation. Use when characterizing where in transcripts an RBP binds, comparing peak distribution across regions, generating splicing-regulatory maps relative to alternative-splicing events, or distinguishing exonic vs intronic vs UTR binding.

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Detect syntenic blocks and structural rearrangements between genomes using MCScanX (Wang 2012), JCVI/MCScan (Tang 2008 Python), GENESPACE (Lovell 2022) for orthology-anchored riparian visualization, SyRI for structural variation, AnchorWave for sequence-level synteny, i-ADHoRe 3.0 for highly diverged species, SynNet for synteny networks, and ntSynt for multi-genome macrosynteny. Use when identifying collinear gene blocks across species, distinguishing macrosynteny from microsynteny, detecting inversions/translocations/duplications, anchoring orthology in WGD lineages, producing publication riparian plots, computing synteny block age via Ks (cross-references whole-genome-duplication), or running synteny-aware ortholog inference in polyploids.

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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 DTL+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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Identify differentially bound regions across CLIP-seq conditions (knockdown vs control, treatment vs vehicle, disease vs healthy) using DEWSeq (sliding-window DESeq2), Flipper (Skipper-downstream), ASpeak, edgeR, or limma-voom. Use when computing condition-level changes in RBP binding intensity, choosing peak-level vs window-level vs crosslink-level testing, designing replicate experiments, or distinguishing biological binding shifts from technical confounders.

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Align preprocessed CLIP-seq reads (eCLIP, iCLIP, iCLIP2, PAR-CLIP) to genome with STAR or bowtie2 using crosslink-preserving parameters, choosing between unique-mapper-only and multi-mapper-aware alignment for repeat-binding RBPs, deciding STAR vs HISAT2 memory trade-offs, and applying ENCODE-compatible filters. Use when turning preprocessed CLIP FASTQ into a deduplicated, MAPQ-filtered BAM ready for peak calling or crosslink-site detection.

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Identifies super-enhancers from H3K27ac, MED1, or BRD4 ChIP-seq using ROSE, ROSE2, LILY, HOMER -style super, and ENCODE dELS cross-referencing. Handles peak stitching parameters, ranking choices, hockey-stick inflection, marker choice (H3K27ac vs MED1/BRD4), and cross-condition comparison with spike-in normalization. Constructs core regulatory circuitry (Saint-Andre 2016) from SE-encoded TFs. Use when identifying cell-identity / cancer-associated regulatory domains, comparing super-enhancers between conditions, identifying master transcription factor networks, or predicting BET-inhibitor responsiveness.

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Performs structure-based virtual screening using AutoDock Vina, SMINA, GNINA (CNN scoring), and DiffDock-L hybrid workflows with explicit choice rules across rigid vs flexible docking, cross-docking vs self-docking, binding-site detection (P2Rank, fpocket), receptor preparation (PDB2PQR, PROPKA), ligand preparation (meeko, OpenBabel), and ultralarge-library screening (ZINC22, Enamine REAL). Use when screening chemical libraries against a protein target to find candidate binders, ranking docking poses, or selecting a docking workflow for a specific scenario.

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Use this skill when the user asks about US-Canada cross-border CMV operations — CVOR (Commercial Vehicle Operator's Registration), NSC (National Safety Code), Ontario / Quebec / BC specific rules, US carrier obtaining Canadian operating authority, FAST card for drivers, customs (CBSA), Health Canada hazmat, and how Transport Canada equivalents differ from US FMCSA. Reference USMCA + Transport Canada NSC 14.

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Use when a carrier asks about disaster recovery (DR) and business continuity planning (BCP) — cyber incident, natural disaster, terminal loss, key-person departure, financial liquidity event, major customer loss, insurance crisis, or fuel supply disruption. Covers risk assessment, continuity strategy, communication plans, and recovery time objectives.

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Drafting and iterating sections of The Federated Harbor whitepaper — the third paper in the Curiositech sequence after Anchor (local identity) and Bonded Commons (local coordination), extending coordination across machines and administrative domains. Use when authoring a section, rewriting a section after a redteam/whitehat round, or composing a new chapter. NOT for marketing copy, NOT for the other two papers, NOT for production threat response.

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Long-running design anthropologist that builds comprehensive visual databases from 500-1000 real-world examples, extracting color palettes, typography patterns, layout systems, and interaction design across any domain (portfolios, e-commerce, SaaS, adult content, technical showcases). This skill should be used when users need exhaustive design research, pattern recognition across large example sets, or systematic visual analysis for competitive positioning.

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Tracks cumulative LLM costs across DAG execution and makes real-time decisions to stay within budget. Downgrades models, skips optional nodes, or stops early when cost exceeds thresholds. Use when managing execution budgets, analyzing cost breakdowns, or optimizing model routing for cost. Activate on "cost budget", "too expensive", "reduce cost", "cost optimization", "model downgrade", "budget exceeded". NOT for LLM model selection logic (use llm-router), pricing comparisons across providers, or billing/invoicing.

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Plan or audit the cross-layer Harbor cooperative editor: Loro replicas for humans and agents, governed edit claims, salvage authority, and transport across shared, LAN, and remote harbors. Use when a change spans editor collaboration, identity, recovery, or transport contracts. For a single GPUI pane use gpui-rust-console; for motion use rust-gpui-motion; for a shader use gpui-shaders. NOT for non-collaborative screens, web editors, or generic Rust development.

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Audit a compliance-ladder design (C0-C6) and transcript-fidelity ladder (T0-T5) plus their adapter conformance fixtures — Codex, Claude Code, Cloudflare, Ollama/LM Studio, custom stdio/HTTP agents — for the two failure modes that make a C-badge or T-fidelity label a lie: the ladder disagreeing with itself across doc/schema/ui/probe surfaces, and a level being reachable by self-report because no daemon-witnessed negative probe actually tries to forge it. Use when designing or freezing a compliance ladder, wiring an adapter conformance probe suite, deciding whether a numeric C-badge or T-label is safe to ship, or investigating a self-attestation or observed-to-controlled bypass risk. NOT for auditing a cryptographic protocol or whitepaper for adversarial soundness (`redteam-review`), writing TLA+/formal invariants for a daemon monitor (`runtime-verification-for-agents`), or agent identity, successor linkage, and reputation across restarts (`agent-identity-continuity-reputation`).

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Designs and verifies fail-closed continuation of a living durable agent after its VM, process, provider session, backend, or context window disappears. Use for body leases, generation fencing, cold-birth failure, process GC, native resume, cross-harness rebodiment, resurrection capsules, capability translation, ambiguous-effect reconciliation, and capacity-aware handoff. NOT for reviving an intentionally retired identity, generic disaster recovery, copying credentials or raw transcripts, ordinary process restart, or claiming metaphysical continuity.

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End-to-end Coval accent testing workflow. Creates one persona per accent (each using a distinct accent voice and mirroring your Standard Customer behavior), launches one run per accent against the same voice agent + test set + metrics, polls for completion, builds a per-persona comparison table from the results, and creates the saved multi-run report (grouped by Persona) via the public API. Use when a user wants to follow the Testing Across Accents cookbook (https://docs.coval.dev/guides/testing-across-accents) without doing each step by hand.

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End-to-end Coval audio-quality testing workflow. Launches one run per audio-robustness scenario against the same voice agent + test set + metrics, polls for completion, and produces the multi-run report URL grouped by Persona. Use when a user wants to follow the Testing Across Audio Qualities cookbook (https://docs.coval.dev/guides/testing-across-audio-qualities) without doing each step by hand.

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Maps intelligence for local SEO: geo-grid rank tracking, GBP profile auditing via API, review intelligence across Google/Tripadvisor/Trustpilot, cross-platform NAP verification, competitor radius mapping, and LocalBusiness schema generation. Three tiers: free (Overpass + Geoapify), DataForSEO, and DataForSEO + Google. Use when user says "maps", "geo-grid", "rank tracking", "GBP audit", "review velocity", "competitor radius", or "SoLV".

日本語の概要は準備中です。原文の説明を表示しています。