78 件 ・ 関連度順
概要と使いどころ
Predict TCR-epitope specificity using ERGO-II and deep learning models for T-cell receptor antigen recognition. Match TCRs to their cognate epitopes or predict TCR targets. Use when analyzing TCR repertoire specificity or identifying antigen-reactive T-cells.
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Predict CRISPR off-target sites using Cas-OFFinder and CFD scoring algorithms. Identify potential unintended cleavage sites genome-wide and assess guide specificity. Use when evaluating guide RNA specificity or selecting guides with minimal off-target risk.
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Infer or annotate TCR antigen specificity by unsupervised clustering (TCRdist/tcrdist3, GLIPH2, clusTCR, GIANA) and database lookup (VDJdb, IEDB, McPAS-TCR), and rank candidates with supervised predictors (ERGO-II, NetTCR-2.x, pMTnet) under explicit caveats. Encodes the central truth that general TCR-epitope prediction for UNSEEN epitopes essentially does not work (collapses to near-random; IMMREP22, Grazioli 2022) because labeled data is dominated by a few immunodominant epitopes and there is no true negative set — so clustering for discovery is the honest task and de-novo binding needs wet-lab validation. Use when annotating TCR specificity or grouping a repertoire. Epitope/MHC context lives in mhc-binding-prediction.
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Design a learning sequence teaching prompt quality — comparing vague vs. refined prompts to show why specificity and context transform AI output. Use when students use AI without understanding why output quality varies.
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Writes the one sentence that makes a generic offer feel written for this one company. Produces the tail of "I think we can help you ___". Triggers on "specificity line", "make it feel specific to them", "the specifically sentence", "why would they think this is for them", "personalize the offer not the intro". Outputs one lead-level merge field, blank when the company does not fit.
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临床诊断思维 (临床诊断思维 / 临床推理 (Clinical Diagnostic Reasoning) — 医生『怎么想病』的元学科:从症状/体征/检查到诊断结论的认知操作系统,从业者(临床医生/住院医/规培生,尤其全科/急诊/大内科等以未分化主诉为生的科室)、医学生与医学教育者、诊断安全与质量改进研究者、以及做医疗 AI 辅助诊断产品的人的视角。覆盖: (a) 第一性张力 — **直觉模式识别 (System 1: illness scripts 疾病脚本 / pattern recognition / gestalt, 『资深人一眼认出 aunt Minnie』) ⇄ 分析性推理 (System 2: hypothetico-deductive 假设演绎 / Bayesian 概率更新)** 的 dual-process 双过程理论 (Kahneman→Croskerry/Norman 谱系), 资深≠更会分析而是『脚本库更大+校准更好』; 更深层论战 — **『认知去偏可教 (Croskerry: bias awareness / cognitive forcing strategies / diagnostic timeout) ⇄ 偏倚标签是马后炮、知识结构才是主因 (Norman/Sherbino/Monteiro: debiasing 干预 transfer 证据弱, bias 是 hindsight 标签)』** — 本行最核心学术对垒; 『概率思维 (验前概率 × 似然比 → 验后概率, Pauker-Kassirer test/treatment threshold 阈值模型) ⇄ 穷尽式排查 (rule-out everything / 防御性医疗 / VOMIT)』; 『临床 gestalt ⇄ 结构化临床决策规则 (Wells/PERC/HEART)』; 『诊断简约 Occam's razor ⇄ Hickam's dictum (病人可以同时得 N 个病)』; 『床旁体格检查复兴 (Verghese Stanford 25 / McGee 循证体检) ⇄ 影像检验替代床旁』; (b) 方法论正典 — illness script theory (Schmidt/Boshuizen: enabling conditions/fault/consequences 三段结构), problem representation + semantic qualifiers 问题表征与语义限定词 (Bowen NEJM 2006, 把病人翻成 one-liner), hypothetico-deductive model (Elstein 1978《Medical Problem Solving》: 早期假设生成+定向检验), Bayesian 工具箱 (sensitivity/specificity/LR/Fagan nomogram/SnNout-SpPin), threshold model (Pauker-Kassirer NEJM 1975/1980), 认知偏倚分类学 (anchoring/premature closure/availability/confirmation/base-rate neglect/search satisficing/diagnostic momentum — Croskerry 偏倚清单), 去偏与元认知策略 (diagnostic timeout/cognitive forcing/Ely checklist/calibration), schema-based reasoning (Clinical Problem Solvers schemas: 按 pivot 症状走分支), reflective practice 结构化反思 (Mamede/Schmidt), 诊断错误科学 (NAM 2015 报告定义 / Newman-Toker Big Three / Hardeep Singh e-triggers / SAFER Dx 框架); (c) 行业结构与角色 — 医学生→实习/住院医 (晨会 morning report/查房被 pimping/汇报训练)→主治 attending→master clinician (NEJM CPC discussant/晨会大师如 Dhaliwal); 配套生态: 医学教育者 (clinical reasoning curriculum + 评估: script concordance test/key features exam/OSCE), 诊断安全研究者 (SIDM/AHRQ), 诊断辅助与 CDS 工具开发者 (DDx generator/AI); (d) 核心工作流 — 数据采集 (病史为王 + 循证体检 + 针对性检验影像) → 问题表征 (one-liner + semantic qualifiers) → 鉴别诊断生成 (schema / 解剖定位法 / VINDICATE-M 病因筛, 按『常见可能 × 致命不能漏 can't-miss』双轴排序) → 假设定向检验 (按 LR 选检查 / 阈值决策) → working diagnosis + 安全网 (red flags 交代 / test of time / test of treatment) → 反馈校准 (follow-up / M&M / diagnostic timeout); 教学工作流: 晨会渐进披露汇报 / CPC / SNAPPS / one-minute preceptor / virtual morning report; AI 增强工作流 (2023-2026: LLM 鉴别诊断头脑风暴 / OpenEvidence 检索 / ambient scribe 释放认知带宽 + 自动化偏倚 guardrails); (e) 产出物 — one-liner, problem list, prioritized DDx, assessment & plan (按问题分层), 晨会/CPC 汇报, M&M 复盘, 诊断不确定性沟通 (『最可能是 X, 但出现 Y 红旗立刻回来』); (f) 教育与评估 — script concordance test / key feature exam / EPA / 里程碑; 中国语境: 人卫《诊断学》教材 / 执业医师考试 / 规培结业临床思维考核; (g) 争议/批判 — debiasing 之争 (Croskerry vs Norman-Sherbino『knowledge is the cure』, 去偏 RCT 效果弱 / bias 标签不可证伪), 诊断错误率数字之争 (『10-15%』经典估计 / Newman-Toker 79.5 万美国年严重伤害外推方法被质疑 / 尸检符合率), dual-process 二分被批过度简化 (连续谱 / 难以实证分离), 决策规则 vs gestalt (资深 gestalt 常不输 Wells 类规则 / 算法厌恶), vignette 研究外推性 + context/case specificity (推理高度内容绑定不可通用迁移 [Norman/Eva] — 对『教推理通用课』产业的根本批判), AI 辅助诊断 2023-2026 (GPT-4 在 NEJM CPC/vignette 追平或超医生 [Kanjee 2023 JAMA / Goh 2024 JAMA Netw Open『AI alone > physician+AI』悖论] / Google AMIE / OpenEvidence 爆发 vs 自动化偏倚 / 去技能化 / 真实环境验证缺失), 防御性医疗与过度检查 (incidentaloma 瀑布 / VOMIT), 体检衰亡之争, pimping 教学法争议; (h) 流派/思想谱系 — 决策科学/Bayesian 派 (Ledley-Lusted 1959 → Elstein/Kassirer/Sox/Pauker/Eddy → Brush) vs 认知心理/双过程派 (Kahneman-Tversky → Croskerry/Graber) vs 教育认知派 (Schmidt/Boshuizen illness scripts → Norman/Eva/Mamede/Durning 情境认知) vs 诊断安全/系统派 (NAM 2015 / Newman-Toker / Hardeep Singh / Graber-SIDM: 错误=系统×认知共因) vs 床旁临床派 (Osler 传统 → Tierney aphorisms / Verghese / McGee / Dhaliwal / Saint: 病史体检为王 + 刻意练习) vs AI/计算派 (INTERNIST-1/DXplain 专家系统 → Isabel → LLM 世代 Rodman/Topol)。不含: 具体专科治疗方案与手术决策深度 (足踝外科/种植牙等另有 skill), 中医辨证 (另有 skill), EBM 文献批判性评价方法学 (相关但本 skill 聚焦诊断推理本身), 护理诊断体系 (NANDA), 影像/病理知觉型读片训练 (相邻但独立), 精神科 DSM 结构化访谈细节, 医患沟通技巧全集 (只覆盖诊断不确定性沟通), 患者自查/自我诊断指
日本語の概要は準備中です。原文の説明を表示しています。
Design a learning sequence teaching prompt quality — comparing vague vs. refined prompts to show why specificity and context transform AI output. Use when students use AI without understanding why output quality varies.
日本語の概要は準備中です。原文の説明を表示しています。
Write or rewrite prose so it sounds like a human wrote it — not a frontier model. Named in homage to Rabindranath Tagore, whose prose carried what frontier models reach for and miss: a point of view, specificity over abstraction, and restraint over puffery. Merges two complementary approaches: a 29-pattern catalog of AI tells (from humanizer) plus an 8-rule operating system with an 8-dimension scoring gate (extending stop-slop). Use when drafting, editing, or reviewing any prose: essays, posts, docs, reports, emails. Detects and removes inflated symbolism, promotional language, superficial -ing analyses, vague attributions, em dash overuse, rule of three, AI vocabulary, passive voice, negative parallelisms, filler phrases, inanimate-verb constructions, narrator-from-a-distance voice, and metronomic rhythm. Adds back the things AI writing usually lacks: point of view, stakes, specificity, restraint, varied rhythm, and trust in the reader.
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Infer or annotate TCR antigen specificity by unsupervised clustering (TCRdist/tcrdist3, GLIPH2, clusTCR, GIANA) and database lookup (VDJdb, IEDB, McPAS-TCR), and rank candidates with supervised predictors (ERGO-II, NetTCR-2.x, pMTnet) under explicit caveats. Encodes the central truth that general TCR-epitope prediction for UNSEEN epitopes essentially does not work (collapses to near-random; IMMREP22, Grazioli 2022) because labeled data is dominated by a few immunodominant epitopes and there is no true negative set — so clustering for discovery is the honest task and de-novo binding needs wet-lab validation. Use when annotating TCR specificity or grouping a repertoire. Epitope/MHC context lives in mhc-binding-prediction.
日本語の概要は準備中です。原文の説明を表示しています。
Infer or annotate TCR antigen specificity by unsupervised clustering (TCRdist/tcrdist3, GLIPH2, clusTCR, GIANA) and database lookup (VDJdb, IEDB, McPAS-TCR), and rank candidates with supervised predictors (ERGO-II, NetTCR-2.x, pMTnet) under explicit caveats. Encodes the central truth that general TCR-epitope prediction for UNSEEN epitopes essentially does not work (collapses to near-random; IMMREP22, Grazioli 2022) because labeled data is dominated by a few immunodominant epitopes and there is no true negative set — so clustering for discovery is the honest task and de-novo binding needs wet-lab validation. Use when annotating TCR specificity or grouping a repertoire. Epitope/MHC context lives in mhc-binding-prediction.
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Use when reviewing a CSS architecture for specificity issues, setting up a design system, or migrating a large codebase from utility-first to a layered architecture.
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Queries 20+ bioinformatics resources through CLI/Python. Supports quick lookups of gene info, BLAST/BLAT, viral sequence downloads, PDB/mmCIF structures, G2P residue annotations, enrichment analysis, OpenTargets, COSMIC, CELLxGENE, and 8cube mouse specificity/expression data. Best for interactive exploration and simple queries. For batch processing or advanced BLAST use biopython; for multi-database Python workflows use bioservices.
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Plans, executes, and documents validation, verification, and transfer of analytical procedures under the governing framework - ICH Q2(R2) and Q14, USP <1220>/<1225>/<1226>, ICH M10 bioanalytical, CLSI EP, or ISO/IEC 17025. Use for HPLC, LC-MS/MS, GC, CE, ICP-MS, dissolution, qNMR, qPCR, NIR, and ligand binding or cell-based assays whenever the question is whether a procedure is fit for its intended purpose. Triggers include "method validation", "analytical method validation", "AMV", "validation protocol", "acceptance criteria", "linearity", "reportable range", "accuracy and precision", "repeatability", "intermediate precision", "recovery", "LOD", "LOQ", "detection limit", "quantitation limit", "specificity", "robustness", "method transfer", "method comparison", "Deming", "Passing-Bablok", "Bland-Altman", "equivalence testing", "OOS investigation", "ICH Q2", "Q2(R2)", "Q14", "USP 1225", "ICH M10", "incurred sample reanalysis", "ISR", "CLSI EP", and any request to show that an assay works.
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Investigate consistently failing SGLang CI tests by extracting the failure signature from scheduled or rerun workflows, bisecting the passing/failing commit window, checking runner or hardware specificity, and optionally reproducing on a remote GPU host.
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MANUAL TRIGGER ONLY: invoke only when user types /office-hours. YC Office Hours — two modes. Startup mode: six forcing questions that expose demand reality, status quo, desperate specificity, narrowest wedge, observation, and future-fit. Builder mode: design thinking brainstorming for side projects, hackathons, learning, and open source. Saves a design doc. Use when asked to "brainstorm this", "I have an idea", "help me think through this", "office hours", or "is this worth building". Proactively suggest when the user describes a new product idea or is exploring whether something is worth building — before any code is written.
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Transforms vague UI ideas into polished, Stitch-optimized prompts. Enhances specificity, adds UI/UX keywords, injects design system context, and structures output for better generation results.
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Extends a mechanistic or association-level biomedical finding into a staged validation pathway that moves from descriptive evidence toward stronger functional support, mechanistic specificity, and clinical relevance. Use this skill when a user has a pathway, biomarker, cell-state, target, mechanism, or association finding and needs to decide what should be validated next, in what order, and which evidence layers are necessary versus optional. Do not default to maximal validation stacks. Build a structured validation ladder with a primary route, stronger upgrade route, and optional extensions.
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Use to review a generated HTML deck or single-page artifact for visual quality and structural correctness. Especially good at catching CSS specificity bugs where slide-modifier classes (.divider, .center, .q, .flow etc.) accidentally override the base .slide{display:none} and cause one slide to stack on top of every other. Also catches missing keyboard navigation, bullet-dump / wall-of-text failure modes, broken self-containment (external link/script/img). Patches the file in place; never changes the original content (slide text, numbers, named entities are the author's work, not yours).
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Designs and ranks guide RNAs (sgRNAs) for CRISPR-Cas9/Cas12a gene knockout by scanning a target for PAM sites (NGG SpCas9, NNGRRT SaCas9, TTTV Cas12a, NG SpCas9-NG, near-PAMless SpRY), enumerating candidate spacers, applying hard filters (Pol-III TTTT terminator, 5' G, GC), ranking on-target activity with the context-appropriate model (Rule Set 2/Azimuth for U6/lentiviral, CRISPRscan for T7/embryo, DeepHF for high-fidelity variants, DeepCpf1 for Cas12a), and predicting the indel/frameshift outcome (Bae out-of-frame score, inDelphi, FORECasT, Lindel). Use when selecting sgRNAs to knock out a gene, choosing a nuclease/PAM for a constrained locus, picking which exon to target, or shortlisting guides before an off-target check. Off-target specificity, base/prime editing, and HDR donors are separate skills.
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Tracks ctDNA across serial liquid-biopsy timepoints for molecular residual disease (MRD) and treatment-response monitoring, treating MRD as a binary integrated detection call across the patient's full variant set (with a defined LoD95 and per-sample specificity) rather than a per-timepoint VAF threshold, and handling undetectable samples as left-censored at the per-sample limit of detection rather than true zeros. Covers tumor-informed bespoke vs tumor-naive design, landmark vs surveillance sampling, molecular-response definitions and their non-standardization, censoring-aware clearance kinetics, and the multiple-testing structure of repeated surveillance. Use when monitoring ctDNA during therapy, calling molecular relapse before imaging, or estimating clearance half-life from serial samples.
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Nominates and assesses CRISPR off-target sites genome-wide. Enumerates candidate sites by mismatch and bulge tolerance with Cas-OFFinder/CRISPRitz, ranks them with the published CFD score (SpCas9-only, relative ranker) or MIT/CRISTA/energy models, runs variant-aware screening against gnomAD/individual genomes (CRISPRme), and frames the empirical genome-wide discovery assays (GUIDE-seq, CIRCLE-seq, CHANGE-seq, DISCOVER-seq, Digenome-seq) and high-fidelity nuclease choice (HiFi Cas9, Sniper-Cas9, eSpCas9, SpCas9-HF1). Use when assessing guide RNA specificity, choosing among candidate guides, screening a therapeutic guide against population variation, or planning empirical off-target validation. Distinguishes predicted vs detected vs validated. On-target activity scoring and deaminase (Cas-independent) base/prime-editor off-targets are separate skills.
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Infer transcription factor regulons from single-cell RNA-seq with pySCENIC by combining GRNBoost2 co-expression, cisTarget motif-enrichment pruning, and AUCell per-cell activity scoring. Covers the motif-pruning-as-directionality principle, regulon specificity scoring, run-to-run stability, and database/species matching. Use when identifying TF regulons, scoring TF activity per cell, finding master regulators of cell identity, or comparing regulon activity across conditions. For enhancer-driven multiomic GRNs see multiomics-grn; for bulk inference and VIPER protein-activity see grn-inference.
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Discover RBP binding motifs from CLIP-seq peaks or single-nucleotide crosslink sites using HOMER, MEME/STREME, kpLogo, mCross (CL-position-registered motifs), PEKA (positional k-mer enrichment), RBPamp (affinity), and RNA Bind-n-Seq (RBNS) cross-validation. Use when characterizing RBP sequence specificity, registering motifs to crosslink positions, validating in vivo CLIP motifs against in vitro RBNS Kd, reconciling motif disagreements across tools, or correcting for the uracil crosslinking bias that contaminates raw CLIP motif logos.
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Profiles RNA-binding protein targets without antibody or UV crosslinking using STAMP (APOBEC1-RBP fusion, C-to-U editing), scSTAMP (single-cell), TRIBE/HyperTRIBE (ADAR-RBP, A-to-I editing), DART-seq (APOBEC1-YTH for m6A), or Bullseye/SAILOR edit-site detection pipelines. Use when antibody is unavailable or specificity is doubtful, when single-cell RBP profiling is needed (scSTAMP), or when in vivo RBP profiling without UV is preferred.
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