'framework' 검색 결과

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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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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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 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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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 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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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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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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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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Use when a carrier needs to build an internal dispatcher training program, onboard new dispatchers, or certify dispatcher competency. Covers job description, required skills, training modules, certification frameworks (CDS, CTP), shadowing, evaluation, and career path.

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Use this skill when the user asks about driver discipline — when to coach vs warn vs suspend vs terminate, progressive discipline frameworks, at-will employment in trucking, documenting violations, separating "willful violation" from "human error," and how to handle a driver who refuses corrective action. Reference state employment law + ATA SMP.

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Use this skill when the user asks about cybersecurity for a trucking carrier — protecting ELD data, customer information, financial systems, EDI integrations, fleet telematics, ransomware risk, vendor / shipper data sharing, incident response, and FMCSA cyber-recommendations. Reference NIST + CISA cybersecurity frameworks.

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Decision-theoretic framework for agents embedded within the environments they model and act upon

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Frontend stack decisions, Cloudflare deployment patterns, component systems, and internal tools architecture. Use for framework selection, deployment strategy, design system bridging, shadcn setup. Activate on "frontend architecture", "tech stack", "Cloudflare Pages", "component library", "internal tools", "shadcn setup". NOT for writing CSS (use frontend-developer), design critique (use design-critic), or backend APIs.

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Principled action selection for autonomous agents using Expected Free Energy (EFE) under the Active Inference framework. Each candidate action is scored as G(n) = w_prag * (-E[p_n] * damping) + w_epist * (-Var[p_n] * novelty(n)), where agent beliefs are maintained as per-node Beta distributions and updated via Bayesian observation. Selection is a softmax over -gamma * G, making exploration an automatic consequence of uncertainty rather than a hardcoded epsilon. Precision weights w_prag and w_epist self-adapt via surprise history, shifting the agent between exploitation and exploration regimes without any manually tuned schedule.

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End-to-end form handling with react-hook-form, Zod schemas, validation patterns, error messaging, field arrays, and multi-step wizards. Use for complex forms, validation architecture, autosave, field dependencies. Activate on "form validation", "react-hook-form", "Zod", "form error", "multi-step form", "wizard". NOT for simple HTML forms, backend validation only, or non-React frameworks.

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Cloudflare Pages CI/CD with preview environments, edge functions, and Wrangler automation. Activate on: Cloudflare Pages, Wrangler deploy, preview environment, edge function, Pages project, Cloudflare Workers integration, custom domain on Pages. NOT for: Worker-specific development (use cloudflare-worker-dev), DNS management (use devops-automator), full-stack app frameworks (use vercel-deployment).

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Choose, compare, and decompose work into the right coordination topology: dag, workflow, manager-driven team, swarm, blackboard, team-builder, or recurring loop. Use when the coordination shape is unclear, when you need topology-native breakdown instructions instead of a generic DAG, or when planning topology and runtime topology may differ. NOT for actual execution, node-level skill matching, or framework/tool installation.

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Systematic framework for resurrecting and modernizing legacy codebases through archaeology, resurrection, and rejuvenation phases. Activate on "legacy code", "inherited codebase", "no documentation", "technical debt", "resurrect", "modernize". NOT for greenfield projects or well-documented active codebases.

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AWS CDK infrastructure builder using TypeScript with L2/L3 constructs and Well-Architected patterns. Activate on: AWS CDK, CDK construct, CDK stack, CDK pipeline, AWS infrastructure as code TypeScript, L2 construct, CDK patterns. NOT for: Terraform IaC (use terraform-module-builder), Kubernetes manifests (use kubernetes-manifest-generator), serverless framework (use devops-automator).

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Architecture and systems design for agents that retain bounded state across sessions. Covers durable event history, owned state, derived memory, retrieval indexes, framework evaluation, recovery, deletion, and rebuild behavior. Uses constructed implementation examples and workload calibration rather than universal vendor, latency, similarity, retention, or cost claims. Activate on: "always-on agent", "persistent agent architecture", "episodic memory system", "agent memory design", "long-running agent", "stateful agent", "agent that remembers", "MemGPT architecture", "Letta deployment", "/always-on-agent-architecture". NOT for: choosing what data to feed the agent (use always-on-agent-inputs), brainstorming applications (use always-on-agent-applications), safety and privacy concerns (use always-on-agent-safety), general agentic patterns (use agentic-patterns).

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Perform language and framework specific security best-practice reviews and suggest improvements. Use when the user explicitly requests security best practices guidance, a security review/report, or secure-by-default coding help. Trigger only for supported languages (python, javascript/typescript, go), and not for general debugging or non-security tasks.

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Expert knowledge of EU/EEA social security coordination regulations in melosys-api. Use when: (1) Understanding EU Regulation 883/2004 and 987/2009 framework, (2) Understanding personal and material scope of coordination, (3) Understanding coordination principles (single legislation, lex loci laboris), (4) Understanding territorial scope (EU, EEA, Switzerland, UK), (5) Understanding the relationship between Sakstyper.EU_EOS and regulations, (6) Understanding how EESSI integrates with regulation procedures.

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