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Designs and analyzes pooled prime-editor (PE) screens for installing precise genetic variants without bystander confounding. Covers pegRNA design with PRIDICT and PRIDICT2 for predicting per-pegRNA editing efficiency, pegRNA architecture (spacer + scaffold + PBS + RTT), PE2/PE3/PE3b/PEmax variants, MOSAIC in situ saturation mutagenesis, the PRIME pooled-screen methodology (Ren 2023; ~3,699 ClinVar variant screens), chromatin context as a major locus-level determinant of PE efficiency, scaffold-incorporation and indel byproduct quantification with CRISPResso2, and the cross-modal validation strategy of PE + base-editor screens for variant function. Use when designing a pegRNA library for variant installation, choosing between BE and PE for a specific edit, predicting pegRNA efficiency before library synthesis, analyzing PE screen output, distinguishing intended-edit from scaffold-incorporation, or scaling PE screens to thousands of variants.

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Infer integer allele-specific copy number, tumor purity, and ploidy from tumor sequencing by jointly modeling read depth (logR) and B-allele frequency (BAF) with ASCAT, Sequenza, FACETS, PURPLE, and PureCN (tumor-only). Covers the purity-ploidy identifiability problem, the diploid-baseline (dipLogR) anchor, major/minor copy number, loss of heterozygosity, sunrise/contour fit diagnostics, and reconciliation of conflicting fits. Use when tumor analysis needs absolute copy number rather than relative log2, when estimating purity and ploidy, calling LOH or copy-neutral LOH, resolving whole-genome doubling, running tumor-only allele-specific calling, or choosing among ASCAT, Sequenza, FACETS, and PureCN.

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Build a differential-ready consensus peakset from per-replicate ATAC-seq peaks using iterative overlap removal, fixed-width re-centering, and majority-rule overlap. Use when generating a stable peak coordinate system for downstream differential accessibility, ML feature engineering, cross-sample comparison, or fixed-width peak counts; covers Corces 2018 iterative overlap (501 bp), DiffBind summit re-centering, and ENCODE consistency rules.

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Determines whether a patient meets the minimum age requirement (≥18 years or legal age of majority) for genital surgery that includes gonadectomy and/or hysterectomy. Trigger phrase: patient requests gonadectomy or hysterectomy as part of gender-affirming genital surgery.

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Recommends hydrocortisone stress dosing during the active phase of labor for pregnant patients with primary adrenal insufficiency, using a regimen similar to major surgical stress. Trigger phrases: "active phase of labor", "cervix dilation ≥4 cm", "contractions every 5 minutes", "PAI patient in labor".

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Recommends adjusting glucocorticoid doses on the day of surgery based on illness severity and magnitude of surgical stress. Triggers when managing a patient requiring surgery needing perioperative glucocorticoid management, such as "patient on HC for central AI undergoing major abdominal surgery" or "patient with hypopituitarism scheduled for minor procedure".

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AI-driven data extraction from 55+ Actors across all major platforms. This skill automatically selects the best Actor for your task.

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Architect systems like Fable 5 — deep understanding before design, modular thinking, iterative refinement. Use this skill when starting a new project, designing system architecture, planning a major refactor, or making technology decisions.

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Use when completing tasks, implementing major features, or before merging to verify work meets requirements

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Validates a plan before committing to it - checks whether the ranking survives the assumptions, finds the most likely way it fails, and makes the trade-offs explicit via a Pareto frontier instead of an invented single score. Use before a launch, price change, migration, infrastructure change or major commitment, when running a premortem, when two objectives conflict, or when a decision depends on an assumption nobody has tested.

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Bump the package version and create an annotated git tag. Accepts a semantic version number (1.2.0) or a bump type (patch, minor, major). Does not push — use the publish skill to push. Use as part of a release workflow.

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Use when completing tasks, implementing major features, or before merging to verify work meets requirements

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Domain-Driven Design system for software development. Use when designing new systems with DDD principles, refactoring existing codebases toward DDD, generating code scaffolding (entities, aggregates, repositories, domain events), facilitating Event Storming sessions, creating bounded context maps, or performing code reviews with a DDD lens. Covers both strategic design (bounded contexts, subdomains, context maps, ubiquitous language) and tactical design (entities, value objects, aggregates, domain services, repositories). Supports all major architecture patterns (Hexagonal/Ports & Adapters, CQRS, Event Sourcing, Clean Architecture) with language-agnostic guidance and concrete examples in Python and TypeScript.

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学术论文审稿意见回复信。输入是审稿人意见全文、reviewer comments、major/minor revision letter、或既有的 rebuttal 草稿时使用。功能包括：意见拆解 + ID 分配 + 行动映射（classify）、起草 point-by-point 回复（draft）、润色既有草稿（polish）、防御性与真实性审查（audit）、起草给编辑的 cover letter（cover）。覆盖期刊与会议 rebuttal、4 种困难场景（矛盾意见、不可能实验、缺关键证据、minor revision）。不适用于：正文段落写作（用 academic-writing）、图表生成（用 academic-figure）、参考文献格式（用 academic-citation）。

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All agents have equal voice; decisions made by majority vote.

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Use when completing tasks, implementing major features, or before merging to verify work meets requirements

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SOP for locating, auditing, and importing production-tested reference patterns and peer-reviewed literature. Trigger when: - Designing or implementing non-trivial algorithms, system protocols, design patterns, or major library integrations. - Prompt contains: prior art, reference implementation, research patterns, standard implementation, arXiv, RFC.

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The case-law chronicle of this repo's major failures — symptom, root cause, evidence, status, and the rule each battle minted — so nobody re-fights a settled battle or re-proposes a rejected fix. Use when a bug/incident looks familiar ("didn't this happen before?"), when you're about to propose an approach that may have been tried and rejected (e.g. shipping a migration from a package), when someone asks "why does rule X exist" / "why is done-by-lgtm a thing" / "what was incident 988", or when a bug-archaeology run hits the shallow-clone wall and needs the pre-June-2026 history. Trigger phrases: "has this broken before", "why can't packages ship migrations", "why did graduation fail", "why is the green-build lesson a rule", "what did we learn from incident NN". (For a live "build is green but the app is broken" symptom, start at crouton-diagnostics-index. NB keep this description free of any space-then-hash sequence — an unquoted YAML scalar treats space-hash as a comment start and silently truncates.)

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Stress-test plans before committing by imagining they've already failed. Three modes. Diagnostic mode runs a full pre-mortem session — vivid failure scene-setting, six failure categories, the monkey test, and concrete plan adjustments. Review mode checks previous findings monthly for changed probabilities and new failure modes. Alert Triggers mode defines and monitors early warning signals across four trigger categories. Use before any major commitment — strategy, investment, product launch, partnership — or regularly to keep assumptions honest. The planning fallacy is real. The spreadsheet looked great so everyone stopped thinking. This is the antidote. Based on practice by Eterdis (eterdis.com).

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AI-driven data extraction from 55+ Actors across all major platforms. This skill automatically selects the best Actor for your task.

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Simulates academic peer review, evaluating papers across Originality, Methodology, Results, and Writing to provide Major/Minor Revision recommendations with actionable feedback. Triggers when a user asks to "review my paper," "simulate peer review," or "give my paper a peer review.

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Conduct a defensible cybersecurity risk assessment using the NIST SP 800-30 Rev 1 methodology: prepare scope and a risk model, identify threat sources and threat events, identify vulnerabilities and predisposing conditions, determine likelihood and impact, compute risk, and communicate results as a prioritized risk register. Use when an organization needs an actual risk *assessment* (not a maturity score), when a control framework (CSF, ISO 27001, RMF, SOC 2, PCI) requires a documented risk analysis as input, when leadership asks "what are our top risks and how bad are they", when assessing risk for a new system or major change, or when building a risk register from scratch. This is the methodology that feeds framework selection, ATO packages, and treatment decisions. Keywords: risk assessment, NIST 800-30, threat modeling, likelihood and impact, risk register, risk analysis, threat sources, vulnerabilities, risk determination, qualitative risk, risk matrix, residual risk, risk treatment.

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Create, verify, transfer, and resume compact project handoff packets for long-running Codex work. Use after a second observed automatic context compaction, immediately after a third compaction, when attention or constraints degrade, a major phase ends, the user asks to move work into a fresh task, work must pause, or an existing handoff needs to be imported. Do not interrupt after the first normal compaction. Always ask before creating a new task, transfer the global roadmap only after explicit consent, preserve the old task title when available, then require the fresh task to ask what work matters most. Preserve objectives, constraints, decisions, evidence, approval boundaries, workspace state, validation, and risks without treating an old summary as current truth.

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Analyze a local codebase and infer the architecture it is actually using, including repo kind, best-fit dominant architecture, directly evidenced coexisting patterns, major subsystem exceptions, confidence, docs-vs-code drift, and repo-fit hints for downstream agents. Use when prompts ask what architecture a repo uses, whether it is really hexagonal or just layered, what subtle patterns shape a repo or slice, how a target slice fits a hybrid monorepo, whether documented architecture matches implementation, or when `/tw-tk` needs a repo-dialect preflight before making a minimal change.

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