「method」の検索結果

Detect positive (diversifying / episodic / pervasive) selection using codon dN/dS frameworks. Implements PAML codeml site models (M0/M1a/M2a/M7/M8/M8a), branch models, branch-site model A (Zhang 2005), and HyPhy methods (BUSTED, BUSTED-S, BUSTED-MH, BUSTED-PH, MEME, FEL, FUBAR, aBSREL, SLAC, RELAX, GARD, FUBAR-MH). Includes McDonald-Kreitman framework (asymptotic alpha, impMKT, polyDFE, DFE-alpha, GRAPES) for within-species + divergence inference, RERconverge for trait-correlated rate shifts, CSUBST for convergent substitution, and PhyloAcc for accelerated noncoding evolution. Use when testing adaptive evolution at codons, branches, or full gene; running GARD recombination pre-screen; controlling alignment-error and gBGC false positives; reconciling PAML vs HyPhy results; or performing genome-scale selection scans.

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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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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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Normalize read-depth copy-ratio profiles and segment them into copy-number regions using circular binary segmentation (CBS, DNAcopy), hidden Markov models, HaarSeg, and fused-lasso methods. Covers GC-content, mappability, and replication-timing (wave-artifact) bias correction, panel-of-normals/PCA denoising, diploid-baseline centering, and algorithm selection by sequencing depth and event size. Use when choosing a segmentation algorithm, correcting depth bias, diagnosing oversegmentation or a mis-centered baseline, tuning CBS or HMM parameters, or understanding why a downstream CNV caller produced fragmented or shifted segments.

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Detect single-nucleotide crosslink (CL) sites in CLIP-seq data using truncation patterns (iCLIP/eCLIP CITS), crosslink-induced mutations (HITS-CLIP CIMS deletions, PAR-CLIP T-to-C), or HMM/kernel-density methods (PureCLIP, PARalyzer, CTK). Use when single-nucleotide resolution is required for motif registration (mCross), allele-specific binding (BEAPR), variant-effect prediction, or comparing crosslink chemistry across CLIP variants.

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Designs Bayesian clinical trials including Phase I dose-finding (BOIN, CRM, EWOC, mTPI-2), meta-analytic-predictive (MAP) priors with robust mixtures for external data borrowing, EXNEX for basket trials, hierarchical models for safety AE (Berry-Berry), Bayesian platform trials (I-SPY 2, GBM AGILE, REMAP-CAP), and posterior probability stopping rules. Covers FDA Bayesian Devices Guidance (2010), FDA Bayesian Methodology in Drugs Draft (January 2026), BOIN Fit-for-Purpose qualification (December 2021), and Project Optimus dose-optimisation. Use when designing dose-finding studies, platform trials, or sensitivity analyses with informative priors.

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Performs molecular similarity searching using Tanimoto, Tversky, Dice, and cosine coefficients on bit/count fingerprints with explicit choice rules for symmetric vs asymmetric measures, scaffold-hopping vs lead-optimization regimes, activity-cliff diagnosis, and large-library nearest-neighbor methods (BulkTanimoto, Annoy MHFP6, USRCAT). Use when ranking compounds by structural resemblance to a query, clustering libraries, finding analogs, or diagnosing activity cliffs.

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Trains and applies base-resolution deep learning models on ChIP-seq / ChIP-nexus / CUT&RUN data. Uses BPNet (Avsec 2021 Nat Genet 53:354; soft motif syntax from ChIP-nexus), chromBPNet (Pampari A et al 2025 Nat Genet; bias-factorized base-resolution profiles), EnFormer (Avsec 2021 Nat Methods 18:1196; 196 kb input, ~100 kb effective receptive field), DeepSEA (Zhou 2015; multi-task CNN), and JASPAR 2026 deep-learning collection (1259 BPNet ChIP models). Performs in silico mutagenesis for variant-effect prediction, DeepLIFT/Grad attribution, and TF-MoDISco motif discovery from attribution scores. Use when predicting variant effects on TF binding, discovering soft motif syntax / cooperativity, integrating ChIP-seq with sequence-only predictions, or applying precomputed JASPAR Deep Learning models to new variants.

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Analyzes alternative splicing at single-cell resolution. The first decision is library chemistry — 10X 3' is fundamentally limited (RT primes from poly-A, R2 falls in 3' UTR, <0.1 junction read per cell per AS event). Plate-based full-length methods (Smart-seq3, FLASH-seq, VASA-seq, STORM-seq) and single-cell long-read (MAS-Iso-seq, scISOr-Seq2) are the chemistries that give per-cell isoform structure. Tools include MARVEL (R, Smart-seq integrated), BRIE2 (Bayesian PSI with regulatory features and ELBO_gain test), scQuint (junction-cluster, plate-based; not for 10X), SpliZ (annotation-free Z-score), Psix (graph-smoothness regulated AS), and Sierra (alternative polyadenylation, often confused with AS). Use when analyzing isoform usage in scRNA-seq, identifying cell-type-specific splicing, or determining whether scRNA-seq chemistry supports splicing analysis at all.

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Test whether two or more traits share a causal variant at a locus using Bayesian colocalization (coloc.abf, coloc.susie, HyPrColoc, moloc, eCAVIAR, SMR/HEIDI, PWCoCo, SharePro). Use when integrating GWAS with eQTL/sQTL/pQTL/mQTL, distinguishing shared causal variants from LD-driven coincidence, handling allelic heterogeneity, choosing between single-causal vs multi-causal methods, picking PP.H4 thresholds, running sensitivity over p12, or harmonising summary statistics for colocalization.

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Provides comprehensive testing patterns for Spring Boot applications covering unit, integration, slice, and container-based testing with JUnit 5, Mockito, Testcontainers, and performance optimization. Use when writing tests, @Test methods, @MockBean mocks, or implementing test suites for Spring Boot applications.

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Use when implementing authentication, authorization, JWT tokens, security filters, password encoding, or any Spring Security configuration. Covers stateless JWT auth, token rotation, RBAC, and method-level security.

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Reflection-first problem solving methodology for Convex development. Use before implementing any solution to ensure proper root cause analysis, 98% code confidence, and minimal change scope.

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Parameter-efficient fine-tuning for LLMs using LoRA, QLoRA, and 25+ methods. Use when fine-tuning large models (7B-70B) with limited GPU memory, when you need to train <1% of parameters with minimal accuracy loss, or for multi-adapter serving. HuggingFace's official library integrated with transformers ecosystem.

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Remove refusal behaviors from open-weight LLMs using OBLITERATUS — mechanistic interpretability techniques (diff-in-means, SVD, whitened SVD, LEACE, SAE decomposition, etc.) to excise guardrails while preserving reasoning. 9 CLI methods, 28 analysis modules, 116 model presets across 5 compute tiers, tournament evaluation, and telemetry-driven recommendations. Use when a user wants to uncensor, abliterate, or remove refusal from an LLM.

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Use this skill when the user requests to review, analyze, critique, or summarize academic papers, research articles, preprints, or scientific publications. Supports comprehensive structured reviews covering methodology assessment, contribution evaluation, literature positioning, and constructive feedback generation. Trigger on queries involving paper URLs, uploaded PDFs, arXiv links, or requests like "review this paper", "analyze this research", "summarize this study", or "write a peer review".

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Use this skill instead of WebSearch for ANY question requiring web research. Trigger on queries like "what is X", "explain X", "compare X and Y", "research X", or before content generation tasks. Provides systematic multi-angle research methodology instead of single superficial searches. Use this proactively when the user's question needs online information.

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Set up GitHub authentication for the agent using git (universally available) or the gh CLI. Covers HTTPS tokens, SSH keys, credential helpers, and gh auth — with a detection flow to pick the right method automatically.

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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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Use when the user wants a full feature action plan (backend + frontend + tests) with the PWDEVIA 7-question method before any code is written — 'planejar a feature X', 'criar plano de feature', 'plan the user CRUD'. Interviews the human (max 2 rounds) and writes .planning/feat/features/{slug}/plan.md. Do NOT use to write code (feat-exec), for small 1–3 file changes (feat-quick), backend-only or UI-only scope (feat-backend / feat-frontend), tests for existing code (feat-test) or code review (feat-review).

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Use when the user wants a backend-only action plan — API endpoints, services, models, migrations, jobs and their tests — 'plano de backend para o endpoint X', 'plan the orders API'. Writes .planning/feat/features/{slug}/plan.md with the PWDEVIA method. Do NOT use for UI work (feat-frontend), full features spanning backend and UI (feat-feature), writing code (feat-exec) or quick 1–3 file fixes (feat-quick).

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Introduce the cross-section read interface boundary (I<Section>ServiceRead) for one section's service per memory/architecture/section-read-write-split.md. Audits the surface, evaluates which methods belong on the read interface, sets up the workspace, dispatches a subagent that introduces the interface and migrates non-section callers, opens a PR. Use when the user says 'read split for X', 'split <Section>Service', 'add I<Section>ServiceRead boundary', 'apply the section-read-write-split rule to <Section>', or any variation of carving the cross-section read surface out of a section's full service interface. Reference implementation is Teams (PR 678). Operates on one section per invocation.

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Review a local diff or PR for unnecessary durable surface: new files, public types, interface methods, DTOs/view models, helpers, routes, DI registrations, services, repositories, and dependencies that should reuse existing owners instead.

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Break a stuck or complex problem into the smallest sub-question that, if answered, unlocks the next step — then answer it and repeat until the path forward is clear. Load when a problem feels genuinely stuck, when reasoning keeps circling, or when deep-thinking diagnoses a Socratic frame. Also triggers on "I keep going in circles", "what is the real question here", "help me reason through this step by step", "unstick my thinking", "recursive questioning", "what is the root question". Based on the recursive Socratic questioning method (EMNLP 2023) which outperforms CoT and Tree-of-Thought on complex reasoning tasks.

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