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Turns Hi-C/Micro-C FASTQ into a deduplicated, filtered .pairs file with pairtools and decides whether the library worked. Covers the bwa mem -SP5M / bwa-mem2 / chromap --preset hic alignment idiom (mates mapped as independent single-end reads), pairtools parse vs parse2 and the walks-policy choice (5unique pairwise vs all for Pore-C/Micro-C concatemers), pair-type classification (keep UU and rescued UC), dedup (PCR vs optical/by-tile), select by pair_type/MAPQ/distance, restriction-fragment handling (restrict, Arima dual-enzyme, Micro-C/DNase fragment-free), and allele-specific phasing (pairtools phase to two coolers). The library-QC decision uses % long-range cis as the one-number quality metric, trans as the noise floor, orientation balance as fragment-map-free dangling-end/self-circle QC, and % duplicates as a complexity proxy. Use when processing Hi-C/Micro-C/Omni-C reads into pairs, judging library quality, handling multi-enzyme or restriction-agnostic protocols, or generating allele-specific contacts.

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Corrects fluorophore spillover (conventional compensation) or spectral overlap (spectral unmixing) and applies variance-stabilizing transforms (logicle/biexponential, arcsinh, log) for flow and mass cytometry. Covers spillover-matrix estimation from single-stain controls, AutoSpill, the spillover spreading matrix and why panel design (not compensation) bounds resolution, compensate-then-transform ordering, and arcsinh cofactor choice (5 for CyTOF, ~150 for fluorescence, per-channel via flowVS). Use when correcting spectral overlap, preparing data for gating/clustering, choosing logicle vs arcsinh, deciding a cofactor, or distinguishing compensation from spectral unmixing.

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Calculates statistical power for high-dimensional genomics experiments (bulk RNA-seq, scRNA-seq, ATAC-seq, ChIP-seq, methylation, proteomics) under negative-binomial count models using RNASeqPower, PROPER, and simulation via powsimR, distinguishing per-gene from marginal (transcriptome-wide) power, the role of mean expression and dispersion, and the sequencing-depth-versus-replicate tradeoff. Covers simulation as the honest default for overdispersed counts, FDR-aware average power versus single-test power, observed/post-hoc power as an anti-pattern, and the winner's-curse / Type-S / Type-M consequences of underpowering. Use when planning replicate number for a sequencing experiment, deciding whether to add depth or samples, choosing closed-form versus simulation power, estimating power from pilot dispersions, or justifying replication in a grant. For clinical-trial power see clinical-biostatistics/power-and-sample-size; for the inverse sample-size question see experimental-design/sample-size.

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Aligns and QCs methylated-RNA-immunoprecipitation (MeRIP / m6A-seq) IP and input libraries using STAR or HISAT2 splice-aware mapping, samtools sort/index, IP/input matched-pair tracking, antibody-lot metadata recording, replicate concordance via deepTools multiBamSummary + plotCorrelation, IP enrichment QC via plotFingerprint and per-transcript IP/input ratio distributions, library-complexity saturation curves via PreSeq c_curve / lc_extrap, and the explicit do-NOT-deduplicate convention for standard non-UMI MeRIP. Use when preparing paired IP and input BAM files for exomePeak2 / MeTPeak / MACS3 peak calling, evaluating MeRIP replicate concordance and IP enrichment, deciding whether to deduplicate (standard MeRIP typically NOT — see Tips), choosing genome-vs-transcriptome alignment for downstream peak vs m6Anet workflows, recording antibody clone and lot metadata for downstream cross-batch reconciliation, detecting failed IPs via saturation curves and IP/input distribution shape, or generating IP-over-Input bigWig tracks for downstream visualisation.

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Estimates time-scaled phylogenies, molecular clock rates, effective reproduction number R_e (or R_t), and population dynamics from dated pathogen genomes using TreeTime (maximum-likelihood) and BEAST2 (Bayesian; strict / uncorrelated lognormal / ORC clocks; constant / exponential / Bayesian Skyline / Skygrid / BICEPS / Birth-Death-Skyline / sampled-ancestor BDSKY priors; structured coalescent via MASCOT). Covers root-to-tip clock signal QC via TempEst, date-randomisation tests (Ramsden 2009; Duchêne 2015), recombination masking via Gubbins and ClonalFrameML before clock inference for recombining bacteria, BDSKY origin-vs-rootHeight pitfalls, sampling-bias correction (Volz & Frost 2014; preferential-sampling extensions), MASCOT structured coalescent for migration, BICEPS-vs-BSP skyline choice, multi-chain BEAST2 convergence diagnostics, and reconciliation between phylodynamic R_e and case-based R_t. Use when dating outbreak origins, estimating substitution rates, inferring R_e through time, building time-calibrated Nextstrain Augur trees, choosing between strict and relaxed clocks, fitting Birth-Death-Skyline (Stadler 2013) models, diagnosing temporal-signal failure, masking recombination before clock inference for *Streptococcus pneumoniae* / *Neisseria gonorrhoeae* / *Klebsiella* / *E. coli* phylodynamics, running MASCOT for structured-population analyses, or using UShER for pandemic-scale placement.

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Infers person-to-person transmission from pathogen genomes using outbreaker2 (Campbell 2018), TransPhylo (Didelot 2017), phybreak (Klinkenberg 2017), BadTrIP (De Maio 2018), SCOTTI (De Maio 2016), BEASTLIER (Hall 2015), and SNP-distance / cluster-picker approaches (HIV-TRACE for HIV; transcluster). Defines outbreak clusters using pathogen-specific SNP thresholds (NOT a universal cutoff -- TB <=12 SNPs / Walker 2013; MRSA <=15 / Coll 2017; C. difficile <=2 / Eyre 2013; Klebsiella <=21 / Snitkin 2012), models within-host diversity and transmission bottlenecks (Worby-Lipsitch-Hanage 2014; McCrone 2018; Sobel Leonard 2017; Lythgoe 2021 SARS-CoV-2), integrates contact-tracing data, distinguishes generation interval from serial interval (Britton & Scalia Tomba 2019; Ali 2020), attributes source via Bayesian source attribution (Mather 2013 DT104; islandR), and reconciles transmission-network reconstruction with epi metadata. Use when investigating outbreaks for who-infected-whom, defining SNP-cluster outbreak definitions, accounting for unsampled intermediates, choosing between outbreaker2 (rich epi data) and TransPhylo (genomic-only after dated phylogeny), running source attribution between host populations, calling HIV-TRACE thresholds appropriate to the local subtype, or distinguishing recent transmission from reactivation in TB / chronic HIV.

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Plot per-group distributions of continuous data using boxplots, violins, beeswarms, quasirandom jitter, and raincloud plots with sample-size honesty (Weissgerber 2015), KDE-bandwidth awareness, and N-aware encoding choices. Use when comparing distributions across a small number of groups — expression per cluster, biomarker per arm, scores per condition — and the bar-of-mean default is misleading.

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Designs pooled sgRNA libraries for CRISPR knockout, interference (CRISPRi), activation (CRISPRa), Cas12a multiplex, base-editor, and prime-editor screens. Covers on-target scoring (Rule Set 2, Azimuth, DeepSpCas9, CRISPRon), off-target scoring (CFD, MIT), TSS-relative positioning for CRISPRi/a (Horlbeck, Dolcetto, Calabrese), PAM-variant chemistries, control-guide composition, oligo cloning architecture, and library QC. Use when choosing a genome-wide library (GeCKOv2 vs Avana vs Brunello vs TKOv3 vs Inzolia), designing a focused or paralog-focused custom library, picking CRISPRi vs CRISPRa TSS windows, deciding control-guide proportions, or diagnosing library skew and dropout in a freshly cloned pool.

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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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Detect distant homologs using profile and structure-aware methods that go beyond standard BLAST. Use when sequence identity falls into the twilight zone (<35% pairwise), when BLAST fails to find homologs that should exist, when working at metagenomic scale (DIAMOND, MMseqs2), or when structure beats sequence (Foldseek). Covers PSI-BLAST (iterative PSSM), jackhmmer (iterative HMM), HHblits/HHsearch (profile-profile), DIAMOND, MMseqs2, and Foldseek (3Di structural alphabet, van Kempen 2024).

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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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Detects allele-specific transcription factor or histone modification binding from heterozygous-variant ChIP-seq using WASP (reference-bias filter; mandatory upstream), RASQUAL (joint QTL + bias-corrected testing), BaalChIP (Bayesian beta-binomial with copy-number-aware overdispersion), and AlleleSeq (personalized diploid genome). Handles imprinted-locus awareness, X-inactivation artifacts, cancer copy-number imbalance, and integration with downstream caQTL / bQTL mapping. Use when identifying variants with allelic effects on TF binding, fine-mapping causal regulatory variants, validating deep-learning variant predictions, or characterizing cis-acting regulatory effects.

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Designs adaptive clinical trials including group-sequential (O'Brien-Fleming, Pocock, Lan-DeMets spending), sample-size re-estimation (blinded Friede-Kieser, unblinded Cui-Hung-Wang, Mehta-Pocock promising zone), seamless Phase 2/3 with treatment-arm selection, population enrichment, and response-adaptive randomisation. Covers FDA 2019 Final Adaptive Designs Guidance, FDA 2022 Master Protocols, and ICH E20 Step 2b/3 draft (June 2025, NOT final). Use when planning interim analyses, sample-size re-estimation, or master/platform-trial designs.

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Fits structural equation models to GWAS summary statistics using GenomicSEM (Grotzinger 2019), including common-factor models, confirmatory factor models, ESEM, common-factor GWAS with Q_SNP heterogeneity, multivariate Wald tests, and stratified GenomicSEM partitioned heritability. Reconciles results against MTAG multi-trait analysis. Handles sample overlap via the LDSC sampling-covariance matrix, identifies and resolves Heywood cases, and verifies model fit with CFI / RMSEA. Use when modeling latent genetic architecture across correlated traits, running multivariate GWAS on a shared factor, distinguishing factor-mediated from trait-specific SNP effects, or comparing GenomicSEM common-factor results against MTAG when both depend on accurate sampling covariance.

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自动寻找当前网络环境下最快的 GitHub 代理镜像，用于克隆仓库、下载文件或获取 Release 资产。当需要从 github.com 下载任何内容时使用本 skill——包括 git clone、wget/curl 下载、Release 资产获取等。

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Infer cis-regulatory connections (peak-to-peak co-accessibility) from scATAC-seq using Cicero, ArchR getCoAccessibility, or SCENIC+. Use when linking enhancer accessibility to promoter accessibility, identifying enhancer-gene pairs from chromatin alone (without paired RNA), running gene-regulatory inference combining ATAC + RNA, or comparing predicted regulatory contacts against Hi-C/Micro-C ground truth.

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Design, implement, and review web interface layout, component states, feedback, and motion within the current CodeConductor workflow. Use for concrete web UI work or requested UI audits, not backend-only tasks or native mobile apps.

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Provides fault tolerance patterns for Spring Boot 3.x using Resilience4j. Use when implementing circuit breakers, handling service failures, adding retry logic with exponential backoff, configuring rate limiters, or protecting services from cascading failures. Generates circuit breaker, retry, rate limiter, bulkhead, time limiter, and fallback implementations. Validates resilience configurations through Actuator endpoints.

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Build and configure Laravel 10+ applications, including creating Eloquent models and relationships, implementing Sanctum authentication, configuring Horizon queues, designing RESTful APIs with API resources, and building reactive interfaces with Livewire. Use when creating Laravel models, setting up queue workers, implementing Sanctum auth flows, building Livewire components, optimising Eloquent queries, or writing Pest/PHPUnit tests for Laravel features.

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Provides expert knowledge for building Next.js 15+ applications with the App Router, TypeScript, Server Components, Server Actions, and TanStack Query.

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Provides Event-Driven Architecture (EDA) patterns for Spring Boot — creates domain events, configures ApplicationEvent and @TransactionalEventListener, sets up Kafka producers and consumers, and implements the transactional outbox pattern for reliable distributed messaging. Use when implementing event-driven systems in Spring Boot, setting up async messaging with Kafka, publishing domain events from DDD aggregates, or needing reliable event publishing with the outbox pattern.

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Audits Hibernate database interactions to prevent N+1 query problems in JVM apps.

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Audita calidad de código Kotlin/Spring Boot en este proyecto. Úsalo cuando el usuario pida revisar código, verificar estándares, hacer un code review, auditar calidad, ejecutar linters, verificar cobertura, o antes de hacer commit/PR. También úsalo cuando mencionen KTLint, Detekt, JaCoCo, cobertura, o simplemente digan "revisa el código" / "está listo para commit" / "qué tan bueno está el código".

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Evaluate design from a UX perspective, assessing visual hierarchy, information architecture, emotional resonance, cognitive load, and overall quality with quantitative scoring, persona-based testing, and actionable feedback. Use when the user asks to review, critique, evaluate, or give feedback on a design or component.

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