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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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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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Analyzes CRISPR drug-modifier (chemogenomic) screens with drugZ (Colic et al. 2019 Genome Med), a bidirectional Z-score method that identifies synthetic-lethal sensitizing genes and resistance-conferring suppressor genes from vehicle vs drug comparisons. Covers vehicle-anchored design (not Day-0), the bidirectional Z math giving greater sensitivity to small-effect hits than MAGeCK / STARS / edgeR / RIGER on drug screens, per-gene sumZ and normZ, synth (sensitizer) vs supp (suppressor) FDR, multi-dose handling, integration with control sgRNAs, and comparison with MAGeCK MLE with dose covariate. Use when running a drug-modifier CRISPR screen, identifying sensitizing or resistance genes for a drug candidate, choosing drugZ vs MAGeCK MLE for chemogenomic analysis, troubleshooting low-effect drug screens where MAGeCK lacks sensitivity, or designing a drug-screen layout (vehicle vs drug arms).

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Designs and analyzes combinatorial CRISPR screens covering paired-Cas9 (Big Papi, Najm 2018), enhanced AsCas12a multiplex (enCas12a, DeWeirdt 2021), in4mer 4-guide-array Cas12a (Esmaeili Anvar N et al 2024 Nat Commun 15:3577) and the Inzolia paralog-pair library, paralog-buffering detection (Dede 2020 Genome Biol; Thompson 2021 Nat Commun 12:1302), genetic-interaction (GI) scoring as observed_double_LFC minus expected_additive_double_LFC, synthetic-lethal and synthetic-rescue interaction interpretation, the half-of-essentiality buffered by paralogs phenomenon, multiplex screen statistical analysis with MAGeCK MLE interaction terms, and the relationship to single-cell combinatorial Perturb-seq. Use when designing a paralog or pathway-pair screen, choosing between paired-Cas9 (Big Papi) and Cas12a multiplex (Inzolia), interpreting genetic interaction scores, identifying synthetic-lethal targets for drug development, or scaling beyond single-gene CRISPR screens.

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Summarize a sprint's worth of Claude Code activity — sessions grouped by project (cwd), per-model cost breakdown, token efficiency (cache hit rate, compaction baselines), subagent effectiveness from workflow API, velocity metrics (turn_count, turn_duration_ms), and tool diversity across the sprint.

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Fast, lightweight 2D rendering engine for creating interactive graphics, particle effects, and canvas-based applications using WebGL/WebGPU. Use this skill when building 2D games, particle systems, interactive canvases, sprite animations, or UI overlays on 3D scenes. Triggers on tasks involving PixiJS, 2D rendering, sprite sheets, particle effects, filters, or high-performance canvas graphics. Alternative to Canvas2D with WebGL acceleration for rendering thousands of sprites at 60 FPS.

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Data-driven Scrum Master for sprint health scoring, Monte Carlo velocity forecasting, retrospective analysis, capacity planning, and Tuckman team coaching. Use when facilitating sprint planning, diagnosing velocity, or running retrospectives.

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Agile product ownership for backlog management and sprint execution. Use for writing user stories and acceptance criteria, planning sprints, estimating story points, breaking down epics, or prioritizing a backlog.

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A switch whose knob springs across on toggle — a tactile, satisfying on/off state change. Use for settings/form switches. Honors prefers-reduced-motion (quick linear slide). Trigger on user intent only; keep the spring subtle — never to convey loading/progress.

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Provides R wrappers of several on-target and off-target scoring methods for CRISPR guide RNAs (gRNAs). The following nucleases are supported: SpCas9, AsCas12a, enAsCas12a, and RfxCas13d (CasRx). The available on-target cutting efficiency scoring methods are RuleSet1, Azimuth, DeepHF, DeepCpf1, enPAM+GB, and CRISPRscan. Both the CFD and MIT scoring methods are available for off-target specificity prediction. The package also provides a Lindel-derived score to predict the probability of a gRNA to

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Expert knowledge for Azure Spring Apps development including troubleshooting, best practices, decision making, architecture & design patterns, limits & quotas, security, configuration, integrations & coding patterns, and deployment. Use when configuring ASA networking/security, Tanzu tools, observability/APM, CI/CD deployments, or blue‑green releases, and other Azure Spring Apps related development tasks. Not for Azure App Service (use azure-app-service), Azure Container Apps (use azure-container-apps), Azure Kubernetes Service (AKS) (use azure-kubernetes-service), Azure Functions (use azure-functions).

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Spring Boot best practices and patterns. Use when creating controllers, services or repositories, or when the user asks about Spring Boot layering, wiring, configuration or exception handling. For JPA and Hibernate behaviour, use jpa-patterns instead.

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根据用户提供的页面列表和业务需求，生成基于Vue前端和Java Spring Boot后端的网站构成文档及详细实现方案。

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Configure scheduled tasks and distributed locking with ShedLock in Spring Boot. Use when implementing @Scheduled tasks or distributed locking with ShedLock in Spring Boot.

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Standards for Feign clients and asynchronous messaging with Spring Cloud Stream. Use when implementing Feign HTTP clients or async event messaging in Spring Boot microservices.

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Structure Spring Boot 3+ projects with feature packaging and clean layering. Use when structuring Spring Boot 3 projects, defining layers, or applying architecture patterns.

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Deploy Spring Boot apps with Docker, GraalVM native images, and graceful shutdown. Use when deploying Spring Boot apps as GraalVM native images, containers, or configuring shutdown.

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Write unit, integration, and slice tests for Spring Boot 3 applications. Use when writing unit tests, integration tests, or slice tests for Spring Boot 3 applications.

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Design Spring Boot APIs with OpenAPI, Versioning, and Global Error Handling. Use when designing Spring Boot APIs with OpenAPI specs, versioning, or global error handling.

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Instrument Spring Boot with Micrometer metrics, distributed tracing, and structured logging. Use when adding Micrometer metrics, distributed tracing, or structured logging to Spring Boot.

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Optimize JPA, Hibernate, and database interactions in Spring Boot. Use when implementing JPA entities, repositories, or database access in Spring Boot.

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Spring Boot architecture patterns, REST API design, layered services, data access, caching, async processing, and logging. Use for Java Spring Boot backend work.

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Spring Security best practices for authn/authz, validation, CSRF, secrets, headers, rate limiting, and dependency security in Java Spring Boot services.

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Open, create, read, analyze, edit, or validate Excel/spreadsheet files (.xlsx, .xlsm, .csv, .tsv). Use when the user asks to create, build, modify, analyze, read, validate, or format any Excel spreadsheet, financial model, pivot table, or tabular data file. Covers: creating new xlsx from scratch, reading and analyzing existing files, editing existing xlsx with zero format loss, formula recalculation and validation, and applying professional financial formatting standards. Triggers on 'spreadsheet', 'Excel', '.xlsx', '.csv', 'pivot table', 'financial model', 'formula', or any request to produce tabular data in Excel format.

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