'bli' 검색 결과

Infer integer allele-specific copy number, tumor purity, and ploidy from tumor sequencing by jointly modeling read depth (logR) and B-allele frequency (BAF) with ASCAT, Sequenza, FACETS, PURPLE, and PureCN (tumor-only). Covers the purity-ploidy identifiability problem, the diploid-baseline (dipLogR) anchor, major/minor copy number, loss of heterozygosity, sunrise/contour fit diagnostics, and reconciliation of conflicting fits. Use when tumor analysis needs absolute copy number rather than relative log2, when estimating purity and ploidy, calling LOH or copy-neutral LOH, resolving whole-genome doubling, running tumor-only allele-specific calling, or choosing among ASCAT, Sequenza, FACETS, and PureCN.

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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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Quantify homologous recombination deficiency (HRD) from tumor copy number using the three genomic-scar metrics — loss of heterozygosity (LOH), large-scale state transitions (LST), and telomeric allelic imbalance (TAI) — with scarHRD, and via the whole-genome HRDetect and CHORD models. Covers the genomic instability score, the PARP-inhibitor clinical context, whole-genome-doubling correction, and the scar-versus-state distinction. Use when computing an HRD score for PARP-inhibitor eligibility, deriving LOH/LST/TAI scars from allele-specific copy number, deciding between scar-based and mutational-signature HRD methods, or interpreting an HRD result in a BRCA-reverted or low-purity tumor.

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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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Detect introgression and admixture between species or populations using Dsuite (Malinsky 2021 fast D-statistics), Patterson's D / ABBA-BABA test (Green 2010; Durand 2011), f4-ratio and f-branch statistic (Malinsky 2018), TreeMix (Pickrell & Pritchard 2012), HyDe (Blischak 2018), QuIBL (Edelman 2019), sprime (Browning 2018), Twisst (Martin 2017), PhyloNet (Solis-Lemus 2017) for explicit phylogenetic networks, and qpAdm / qpGraph (Patterson 2012; Lipson 2013). Distinguish introgression from incomplete lineage sorting (ILS), ancestral structure, ghost-lineage admixture, and rate variation. Use when testing inter-species gene flow, dating admixture events, identifying introgressed segments, building phylogenetic networks for reticulate evolution, or applying the ABBAclustering (Koppetsch-Malinsky-Matschiner 2024) framework for divergent-species gene flow.

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Normalizes ChIP-seq data using exogenous spike-in (ChIP-Rx with Drosophila chromatin per Orlando 2014 / Egan 2016; E. coli carryover for CUT&RUN/CUT&Tag). Distinguishes RRPM from Rx-Input scaling, integrates with DiffBind / DESeq2 / edgeR / csaw via sizeFactors and DiffBind library-size vectors, and applies the Patel et al 2024 *Nat Biotechnol* review's failure-mode framework to validate that normalization is correctly applied at the read level (not peak counts). Use when global signal shifts are expected (HDACi, BETi, EZH2i, dosage, target knockdown), when ChIPseqSpikeInFree detects post-hoc shifts, or when validating internal-control regions before publication.

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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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Maps GWAS-implicated loci to candidate effector (causal) genes by integrating variant-to-gene (V2G) features via Open Targets L2G (Mountjoy 2021), MAGMA gene-based association (de Leeuw 2015), FUMA SNP2GENE, cS2G combined SNP-to-gene scores (Gazal 2022), Polygenic Priority Scores (PoPS, Weeks 2023), FLAMES, INQUISIT, DEPICT, and enhancer-gene predictors (ABC, ENCODE-rE2G). Use when narrowing a GWAS lead locus to a candidate causal gene, picking between proximity, eQTL-based, and similarity-based prioritizers, integrating multi-evidence streams (fine-mapping, colocalization, ABC enhancer-gene, distance, chromatin), reconciling discordant L2G vs PoPS calls, prioritizing tissue-specific eQTL evidence, or triangulating across at least three independent lines of evidence for a publication-grade effector-gene nomination.

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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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Visualizes ChIP-seq data using deepTools (computeMatrix, plotHeatmap, plotProfile, bamCoverage, bamCompare), pyGenomeTracks (modern INI-driven track plots), Gviz (R browser-style), EnrichedHeatmap (ComplexHeatmap-based), ChIPseeker tag heatmaps, and IGV batch screenshots. Handles bigWig normalization choices (CPM, BPM, RPGC, spike-in scaled), bamCompare operations (log2 ratio, subtract, SES), k-means clustering of heatmaps for biological subgrouping, and spike-in-scaled tracks for global-shift experiments. Use when generating publication-quality ChIP-seq signal heatmaps, profile plots, genome-browser tracks, or comparing samples visually.

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Audit required bioinformatics command-line tools against Lmod or Environment Modules on Linux HPC clusters, resolve executable and version requirements, and reproducibly deploy missing software through a site-approved EasyBuild, Spack, Bioconda/micromamba, Apptainer, binary, or source-build workflow. Use when Codex must inspect module availability, diagnose a missing or wrong-version bioinformatics tool, install scientific software on Slurm/PBS clusters, publish or validate modulefiles, or produce an auditable and rollback-ready cluster software deployment.

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Create and use BAI/CSI indices for BAM/CRAM files using samtools and pysam. Use when enabling random access to alignment files or fetching specific genomic regions.

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Use this skill when the user asks about towing + recovery operations — separate FMCSA authority class, light-duty vs medium-duty vs heavy-duty wrecker rules, AAA + AAA-Plus contracts, Roadside-Assistance (RA) operations, "non-consensual tow" rules + state-by-state, and how towing operations differ from general freight. Reference state Public Utility Commission + 49 CFR 395 application.

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Use this skill when the user asks how to manage a trucking carrier's public reputation — handling a major accident in the news, social media + Glassdoor + Indeed reviews, customer disputes that escalate, employee disputes, regulator perception, and how to communicate during a crisis. Reference industry PR + crisis communication practices.

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Use this skill when the user asks about Americans with Disabilities Act (ADA) accommodation for CDL drivers — interaction between ADA + FMCSA medical certification, when DOT-disqualifying conditions trigger ADA analysis, reasonable accommodation case examples, employer obligations, and how to handle a driver with a condition that may affect CDL status. Cite Title I ADA + 49 CFR 391.41.

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Structure persuasive speeches and formal arguments in forensic, legal, policy, and competitive debate styles. Use when the user needs to prepare talks, opening or closing arguments, policy pitches, public explanations, debate speeches, or mentions 'forensic speech', 'formal argument', 'persuasive speech structure', 'debate speech', 'opening statement', 'closing argument'. Turns structured claims into audience-tuned persuasive delivery.

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Audit or design server-side indexes, directories, reputations, or aggregates that are DERIVED from traffic a platform witnesses (chain heads, run verdicts, heartbeats, publish activity) so that consent gates the derivation, not merely the read: no shadow index over non-consenting principals, post-consent-only evidence windows, retention bounds and delete-propagation into derived rows, activity-oracle threat modeling, and audit-logged ranking discretion. Use when building a capability directory / whois from witnessed activity, a reputation ledger from settled outcomes, vitals aggregation across tenants, or any "the yellow pages can't lie because they index signatures" feature. Keywords: shadow index, derived index, consent gates derivation, activity oracle, phone book not a log, delist propagation, ranking weight audit, k-anonymous aggregate, subpoena surface. NOT for the consent-screen UX and scope-ladder mechanics themselves (use local-first-tenancy-boundary), reputation scoring math and Sybil economics (use agent-identity-continuity-reputation), or discovery-layer architecture L1/L2/L3 (use agent-discovery-directories-guilds).

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Managing third-party dependencies — version pinning, security auditing, license compliance, update workflows, lockfile management, supply chain security. Activate on "npm audit", "dependabot", "renovate", "pin versions", "dependency update", "supply chain", "license compliance", "lockfile", "security advisory", "typosquatting", "SBOM". NOT for internal monorepo package management (use monorepo-management) or publishing your own packages to npm/PyPI.

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Detects and fixes color contrast violations using WCAG 2.1 guidelines and perceptual analysis. Expert in contrast ratio calculation, color blindness simulation, and providing accessible alternatives. Activate on "check contrast", "color accessibility", "WCAG audit", "readability check", "contrast ratio", "hard to read", "can't see text". NOT for general color theory (use color-theory-palette-harmony-expert), brand color selection (use web-design-expert), or non-visual accessibility (use ux-friction-analyzer).

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Expert in color theory, palette harmony, and perceptual color science for computational photo composition. Specializes in earth-mover distance optimization, warm/cool alternation, diversity-aware palette selection, and hue-based photo sequencing. Activate on "color palette", "color harmony", "warm cool", "earth mover distance", "Wasserstein", "LAB space", "hue sorted", "palette matching". NOT for basic RGB manipulation (use standard image processing), single-photo color grading (use native-app-designer), UI color schemes (use vaporwave-glassomorphic-ui-designer), or color blindness simulation (accessibility specialists).

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Use when designing a background-job system, choosing between BullMQ / Sidekiq / RQ / Temporal / SQS, deciding queue-vs-workflow, sizing concurrency vs rate limits, building dead-letter queues, or making handlers idempotent. Triggers: jobs running twice on retry, lost jobs after worker crash, DLQ filling up, Redis OOM from job backlog, exactly-once requested, "do we need Temporal?", visibility timeout / lockDuration confusion, exponential backoff vs jitter, fan-out fan-in workflows. NOT for outbound webhook publishing (different concerns), receiver-side webhook handling (different concerns), event-streaming/Kafka topology, or in-process async (event loop only).

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Revise the Harbor Book so prose, drawings, and marginalia explain the same argument without unpublished development-document dependencies. Use for chapter additions, substantive rewrites, caption editing, visual exposition, and eliminating internal ADR citations.

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Choosing and operating an HTTP API versioning strategy that doesn't break clients — Stripe's date-based pinned versions, the Deprecation/Sunset header pair (RFC 9745 + RFC 8594), URI vs header vs media-type approaches, and the version-transformer pattern. Grounded in Stripe's published architecture and IETF RFCs. NOT for GraphQL schema evolution, gRPC/Protobuf wire compatibility, database schema migrations, or library/SDK semver.

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Design an agent's handling of obligations, prohibitions, permissions, and conflicts among norms and goals. Use when an autonomous agent must decide which norms apply and what to do when they conflict. NOT for simple fixed policy checks, ordinary BDI commitment design, or organizational metaphor.

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