「ost」の検索結果

Performs logistic regression for clinical trial outcomes (binary, ordinal, multinomial) with marginal-vs-conditional estimand reporting per FDA 2023 covariate adjustment guidance, g-computation/standardisation for marginal effects, modified Poisson for RR, Brant test for proportional odds, Firth penalty for separation, and Hauck-Donner detection. Use when modeling binary or ordinal endpoints in confirmatory or exploratory clinical trials.

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Implements missing-data sensitivity analyses for confirmatory clinical trials including MMRM under MAR (with Kenward-Roger correction), reference-based multiple imputation (J2R, CR, CIR, LMCF per Carpenter-Roger 2013), Permutt delta-adjustment / tipping-point analysis, pattern-mixture identifying restrictions (CCMV, NCMV, ACMV), and the Cro vs Bartlett variance debate. Use when handling missing primary or secondary endpoint data in regulatory submissions following NRC 2010 and ICH E9(R1).

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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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Designs covalent inhibitors and warheads targeting cysteine (most common, 98% of covalent drugs), lysine, serine, threonine, tyrosine, and aspartate residues, with explicit handling of warhead reactivity (acrylamide, chloroacetamide, vinyl sulfone, sulfonyl fluoride, fluorosulfate, aldehyde, boronate, nitrile), reversibility (kinact/Ki, t_residence), glutathione (GSH) stability, intrinsic reactivity assays, and covalent docking (DOCKovalent, GOLD, HCovDock). Use when designing covalent inhibitors for targeted covalent inhibition (TCI), KRAS G12C-style approaches, or rationalizing covalent SAR.

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Annotates ChIP-seq peaks to genomic features, nearest genes, ENCODE candidate cis-regulatory elements (cCREs), and regulatory domains. Uses ChIPseeker (R), HOMER annotatePeaks.pl (CLI), pyranges (Python), GREAT/rGREAT (regulatory domain gene-set enrichment), ChIP-Enrich (locus-length-adjusted), ENCODE SCREEN cCRE classification (PLS/pELS/dELS/CTCF-only/DNase-H3K4me3), and ENCODE-rE2G for cell-type-specific enhancer-gene linking. Handles nearest-TSS vs host-gene ambiguity, promoter window definition, and feature priority. Use when assigning genomic context to peaks, linking enhancer peaks to target genes, classifying peaks against ENCODE cCRE registry, or running gene-set enrichment on peak-associated genes.

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Computes and interprets treatment effect measures (OR, RR, RD, HR, NNT) with calibrated confidence intervals (Wilson, Newcombe, Miettinen-Nurminen, MOVER, profile likelihood, Bender NNT) and reports marginal vs conditional estimands per FDA 2023 covariate adjustment guidance. Use when reporting treatment effects in confirmatory trials, comparing effect sizes across studies, or constructing forest plots.

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Assesses RNA-seq data quality specifically for alternative splicing analysis. QC layers include experimental design audit (library prep, read length, depth, replicates), STAR 2-pass cohort-style alignment, junction saturation curves and discovery plateau detection, novel-vs-known junction ratio diagnostics, junction-overhang distribution, splice-site strength scoring (MaxEntScan intrinsic + SpliceAI context-aware), strandedness verification, GENCODE basic vs comprehensive choice, and rRNA contamination screening. Splicing analysis is more demanding than DGE on read length, depth, library prep, alignment strategy, and annotation choice — failures silently bias PSI estimates and inflate novel-junction false positives. Use when evaluating data suitability for splicing analysis, troubleshooting low event detection, or designing sequencing experiments where AS is a primary endpoint.

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Detects aberrant splicing in single rare-disease patients vs a control panel using FRASER 2.0 (Bioconductor; Beta-binomial autoencoder on Intron Jaccard Index, default delta cutoff 0.1, q hyperparameter), OUTRIDER (gene-level outlier expression via autoencoder denoising), LeafcutterMD (Dirichlet-multinomial outlier mode of LeafCutter for annotation-free junctions), and DROP (Snakemake pipeline integrating FRASER2 + OUTRIDER + monoallelic expression for clinical diagnostics). The statistical model is fundamentally different from differential splicing — single-sample-vs-cohort outlier detection rather than two-group comparison. Standard tool in EU rare-disease (Solve-RD) and NIH UDN programs. Use when applying RNA-seq to undiagnosed Mendelian disease, validating predicted splice variants in clinical samples, or detecting cryptic splicing in disease tissue.

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Detects differential alternative splicing between conditions using rMATS-turbo (binomial LRT on junction counts), leafcutter (Dirichlet-multinomial GLM on intron clusters), MAJIQ V3 deltapsi/HET (Bayesian posterior on LSVs), SUPPA2 (empirical-null on TPM-derived PSI), or Shiba (junction-imbalance-corrected, 2025 SOTA at low coverage). Reports FDR-corrected significance and delta PSI effect sizes. Tools differ in statistical model, annotation dependence, calibration regime, and replicate-count requirements. Use when comparing splicing patterns between treatment groups, tissues, or disease states.

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Validate alignment quality with insert size distribution, proper pairing rates, GC bias, strand balance, and other post-alignment metrics. Use when verifying alignment data quality before variant calling or quantification.

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Select, document, download, and checksum-verify the most appropriate NCBI reference genome on an HPC cluster. Use whenever an analysis needs a reference genome, genome FASTA, genome annotation, assembly accession, or genome index and no exact approved assembly is already available; when a user asks to fetch a species genome from NCBI; or when a pipeline must resolve and cache a reproducible reference assembly on a remote cluster.

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Provides patterns to configure AWS RDS (Aurora, MySQL, PostgreSQL) with Spring Boot applications. Configures HikariCP connection pools, implements read/write splitting, sets up IAM database authentication, enables SSL connections, and integrates with AWS Secrets Manager. Use when setting up RDS connections in Spring Boot, configuring connection pooling, or managing database credentials securely.

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Generates strictly typed Drizzle ORM schemas for PostgreSQL with indexes, foreign keys, and Zod schema deduction.

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Create distinctive, production-grade frontend interfaces with high design quality. Generates creative, polished code that avoids generic AI aesthetics. Use when the user asks to build web components, pages, artifacts, posters, or applications, or when any design skill requires project context.

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Writing style guide for technical content, social media, blog posts, READMEs, git commits, and developer documentation. Optimized to avoid AI detection patterns. Use when writing any content beyond code.

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Guide for building and refactoring a FastAPI + Prefect + PostgreSQL/pgvector analytics pipeline that extracts insights from chat data using LLM classification, embeddings, UMAP/HDBSCAN clustering, and narrative generation. Use this skill whenever working on this project's codebase — including adding features, refactoring, debugging, creating new endpoints, modifying pipeline stages, or reviewing architecture decisions. Also trigger when the user asks about project structure, stack decisions, async migration, or best practices for this specific system.

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Revisa cambios de performance de queries ClickHouse y Postgres (vambe-datascience, CRM, réplicas) contra los errores y aprendizajes de la ronda

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Run Playwright tests at scale with cloud-hosted browsers and integrated Azure portal reporting.

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Companion to atlas-contract. Auto-invoked by its Final Audit on caught drift; also use after Post Reviews or user requests to record a mistake. Distills drift into WHEN/DON'T/INSTEAD clauses, writes to Atlas.md after confirmation.

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Forensic root cause analyzer for Antigravity sessions. Classifies scope deltas, rework patterns, root causes, hotspots, and auto-improves prompts/health.

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Orchestrates Android development tasks including project creation, deployment, SDK management, and enprojectnment diagnostics using the `android` command-line tool.

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Orchestrate autonomous AI development pipelines through your Kanban board (Asana, GitHub Projects, Linear). Manages multi-worker Claude Code dispatch, deterministic quality gates, adversarial review, per-task cost tracking, and crash-proof pipeline execution.

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Arquitecto de Soluciones Principal y Consultor Tecnológico de Andru.ia. Diagnostica y traza la hoja de ruta óptima para proyectos de IA en español.

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Fetch any X/Twitter post as clean LLM-friendly JSON. Converts x.com, twitter.com, or adhx.com links into structured data with full article content, author info, and engagement metrics. No scraping or browser required.

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