「framework」の検索結果

Analyzes single-cell pooled CRISPR screens (Perturb-seq, CROP-seq, Perturb-CITE-seq, ECCITE-seq, multiome) where each cell carries an sgRNA and a scRNA-seq / surface-protein / chromatin readout. Covers experimental design (direct-capture Perturb-seq Dixit 2016 vs CROP-seq 3'UTR-barcoded Datlinger 2017 vs ECCITE-seq vs Multiome), MOI for sgRNA assignment, escaper-cell filtering (Mixscape, Papalexi 2021), SCEPTRE NB GLM + permutation for low-MOI (Barry 2024 Genome Biol 25:124), the Pertpy framework, factor decomposition, genome-scale Perturb-seq (Replogle 2022 Cell, 2.5M cells), and per-perturbation single-cell DE. Use when running a single-cell CRISPR screen, choosing direct-capture vs CROP-seq architecture, filtering escaper cells, performing single-cell DE, integrating Perturb-seq with pathway analysis, scaling to GW CRISPRi via Replogle protocol, or analyzing multi-omics screens.

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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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Classify constitutional (germline) copy number variants for clinical reporting using the 2019 ACMG/ClinGen technical standards points-based framework, with ClassifyCNV and AnnotSV for semi-automated scoring. Covers the separate copy-number-loss and copy-number-gain rubrics, the five-tier classification, ClinGen haploinsufficiency/triplosensitivity and dosage-sensitive regions, de novo and segregation evidence, and population-frequency benign evidence. Use when assigning pathogenic/likely-pathogenic/VUS/likely-benign/benign to a constitutional CNV, scoring a CNV against ACMG/ClinGen criteria, or distinguishing the automatable evidence from the case-specific evidence requiring manual input.

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Performs subgroup and heterogeneous treatment effect (HTE) analyses for clinical trials. Covers Mantel-Haenszel pooling, Breslow-Day, interaction tests in regression, RERI for additive interaction, modern data-adaptive HTE methods (STEPP, SIDES, causal forests, X/R-learners), Bayesian shrinkage (Dixon-Simon, MAP, EXNEX), graphical multiplicity (Bretz-Maurer), and credibility frameworks (Sun BMJ, EMA 2019). Use when analyzing treatment effects across patient subgroups for regulatory submissions or precision-medicine claims.

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Queries gnomAD v4 (807k samples), v3, v2.1.1, and constraint metrics with grpmax FAF95, bottleneck-group exclusion, LOEUF interpretation, SV/CNV/mtDNA catalogs, and Whiffin max-credible-AF framework. Use when filtering rare variants, applying ACMG BS1/BA1, ranking genes by LoF intolerance, or selecting between v2 (GRCh37 + chrX/Y constraint) and v4 (GRCh38 + 807k samples).

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Prioritizes rare-disease variants from trio/quad WES/WGS with de novo (DeNovoGear, Triodenovo), compound-heterozygous phasing (WhatsHap), mosaic VAF tiering, phenotype-driven ranking (Exomiser, Phen2Gene, AMELIE), ClinGen gene-disease validity gating, and ACMG SF v3.2 secondary findings reporting. Use when running diagnostic exome / genome pipelines, identifying candidate Mendelian disease genes, screening for incidental findings, or auditing VUS reclassification cycles. The ACMG/AMP classification framework (PVS1 decision tree, Pejaver PP3/BP4 calibration, Tavtigian point system) is in clinical-databases/acmg-classification.

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Queries ClinVar for variant pathogenicity classifications, ClinGen VCEP curations, and somatic-vs-germline interpretations via REST API, weekly VCF, or bulk XML. Use when determining clinical significance, triangulating conflicting interpretations, or aggregating evidence against the ACMG/AMP framework with ClinGen SVI specifications.

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Computes sample size and power for clinical trials including continuous, binary, and time-to-event endpoints; superiority, non-inferiority, and equivalence designs; FDA 2016 non-inferiority margin selection with M1/M2 framework; Schoenfeld 1981 and Lakatos 1988 for survival; Schuirmann TOST and 80-125% bioequivalence; minimum clinically important difference (MCID) vs δ distinction. Use when justifying trial size in protocol or SAP per CONSORT 2025 item 7.

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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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Analyzes chemical libraries by scaffold using Bemis-Murcko scaffolds, generic frameworks, cyclic skeletons, matched molecular pair (MMP) analysis via mmpdb, R-group decomposition, Free-Wilson analysis, scaffold hopping, and chemotype-aware ML train/test splits. Use when identifying chemotype clusters in a library, deriving SAR transformation rules, decomposing series into R-groups, performing scaffold-balanced QSAR splits, or planning analog campaigns.

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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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Predicts whether a DNA variant alters mRNA splicing using sequence-based deep-learning tools — SpliceAI (10kb context dilated CNN, clinical default), Pangolin (multi-tissue), MMSplice (modular per-region CNN with calibrated ΔPSI), SpliceTransformer/TrASPr (tissue-aware transformers), SpliceVault (empirical 300K-RNA lookup of likely mis-splicing outcomes), CADD-Splice (composite score). Applies the ClinGen SVI 2023 framework for ACMG/AMP variant interpretation (PVS1, PP3, BP4 evidence codes), HGVS splicing nomenclature (c.123+1G>A, c.123-3T>G, r.spl?), extended-window scoring for deep-intronic pseudoexons, tissue-specific predictions, branchpoint variant detection (BPHunter, LaBranchoR), and splice-switching ASO design. Use when interpreting splice impact of clinical variants, prioritizing VUS, identifying deep-intronic pathogenic variants, or designing ASOs.

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Provides distributed transaction patterns using the Saga Pattern for Spring Boot microservices. Use when implementing distributed transactions across services, handling compensating transactions, ensuring eventual consistency, or building choreography or orchestration-based sagas with Kafka, RabbitMQ, or Axon Framework.

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Web Performance Engineering — analyzes Core Web Vitals using the PageSpeed Insights API (PSI v5) and applies the 80/20 principle: identify the 20% of changes that produce 80% of the performance gain. Produces a prioritized markdown report with quantified estimates and framework-specific code. Trigger: When auditing page speed, analyzing Core Web Vitals, or optimizing web performance for any URL.

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Use when building PHP applications with modern PHP 8.3+ features, Laravel, or Symfony frameworks. Invokes strict typing, PHPStan level 9, async patterns with Swoole, and PSR standards. Creates controllers, configures middleware, generates migrations, writes PHPUnit/Pest tests, defines typed DTOs and value objects, sets up dependency injection, and scaffolds REST/GraphQL APIs. Use when working with Eloquent, Doctrine, Composer, Psalm, ReactPHP, or any PHP API development.

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Design, implement, review, and audit Android Jetpack Compose UI/UX for phone interfaces. Use when a request concerns concrete Compose layout, components, interaction, accessibility, or visual behavior. Do not activate for framework or dependency presence alone; non-UI Android work is excluded.

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Provides a structured framework for conducting thorough code reviews covering correctness, security, architecture alignment, performance, and technical debt.

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Build robust, production-grade backtesting systems that avoid common pitfalls and produce reliable strategy performance estimates.

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Architectural decision-making framework. Requirements analysis, trade-off evaluation, ADR documentation. Use when making architecture decisions or analyzing system design.

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Build content-focused websites with Astro — zero JS by default, islands architecture, multi-framework components, and Markdown/MDX support.

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Swiss 网格 / 系统派社交卡 — 精确 / 系统化 / 技术感 / 方法论调性。卡角色含 system 封面 / numbered method / 对比 before-after / KPI tower / 横条 mini-chart / 截图解释 / 证据墙 / 收尾 checklist。用于 framework / checklist / 工具说明 / AI workflow / 产品更新 / KPI 总结。触发："做个方法卡 / 框架卡 / 工具拆解卡 / AI 工具卡 / 系统派结构卡"。NOT 情绪 / 文学 / 图主导卡，NOT 软生活 pastel 风。

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Write comprehensive end-to-end tests that verify complete user workflows, integration between components, and system behavior from user perspective using Playwright, Cypress, or similar frameworks. Use when testing user flows, verifying feature integration, testing across real browsers, ensuring UI interactions work correctly, validating form submissions end-to-end, testing authentication flows, catching regressions, automating QA processes, testing API integrations, or building confidence in production deployments.

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End-to-end Solana development playbook (Jan 2026). Prefer Solana Foundation framework-kit (@solana/client + @solana/react-hooks) for React/Next.js UI. Prefer @solana/kit for all new client/RPC/transaction code. When legacy dependencies require web3.js, isolate it behind @solana/web3-compat (or @solana/web3.js as a true legacy fallback). Covers wallet-standard-first connection (incl. ConnectorKit), Anchor/Pinocchio programs, Codama-based client generation, LiteSVM/Mollusk/Surfpool testing, and security checklists.

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Upgrades existing websites and apps to premium quality. Audits current design, identifies generic AI patterns, and applies high-end design standards without breaking functionality. Works with any CSS framework or vanilla CSS.

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