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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 (Mathis 2023/2024) for predicting per-pegRNA editing efficiency, pegRNA architecture (spacer + scaffold + PBS + RTT), PE2 / PE3 / PE3b / PEmax / PEAR variants, MOSAIC in situ saturation mutagenesis (Hsu JY et al 2024 bioRxiv), the PRIME pooled-screen methodology (Erwood/Doman 2023 Nat Biotechnol 41:885; ~3,699 ClinVar variant screens), chromatin context as a primary 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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Plot per-group distributions of continuous data using boxplots, violins, beeswarms, quasirandom jitter, and raincloud plots with sample-size honesty (Weissgerber 2015), KDE-bandwidth awareness, and N-aware encoding choices. Use when comparing distributions across a small number of groups — expression per cluster, biomarker per arm, scores per condition — and the bar-of-mean default is misleading.

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Cross-method decision tree for calling hits in pooled CRISPR screens. Catalogs statistical models (MAGeCK RRA, MAGeCK MLE, BAGEL2, drugZ, JACKS, Chronos, CERES), experimental designs each is built for, failure modes outside design domain, reconciliation when methods disagree, multiple-testing and effect-size thresholds, the order of operations (count -> QC -> CN-correct -> hit-call -> validate), the second-best-sgRNA conservative rule, and consensus-hit strategy. Use when choosing among MAGeCK / BAGEL2 / drugZ / JACKS / Chronos for a given design, reconciling disagreement across two or three methods on the same screen, deciding whether to require consensus, gating downstream validation by hit-confidence tier, or interpreting unstable hit lists across reruns.

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Performs gene-level association from GWAS summary statistics via genetically predicted tissue expression using FUSION, PrediXcan, S-PrediXcan, S-MultiXcan, UTMOST, MOSTWAS, kTWAS, EpiXcan, TIGAR-V2, and probabilistic fine-mapping with FOCUS and MA-FOCUS. Use when running TWAS from GWAS sumstats, prioritising candidate causal genes from a GWAS lead locus, picking single-tissue vs cross-tissue models, identifying LD-induced TWAS false positives, choosing ancestry-matched prediction weights, fine-mapping co-regulated TWAS hits, or triangulating TWAS with cis-eQTL Mendelian randomization and colocalization to nominate a causal gene.

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Identifies super-enhancers from H3K27ac, MED1, or BRD4 ChIP-seq using ROSE, ROSE2, LILY, HOMER -style super, and ENCODE dELS cross-referencing. Handles peak stitching parameters, ranking choices, hockey-stick inflection, marker choice (H3K27ac vs MED1/BRD4), and cross-condition comparison with spike-in normalization. Constructs core regulatory circuitry (Saint-Andre 2016) from SE-encoded TFs. Use when identifying cell-identity / cancer-associated regulatory domains, comparing super-enhancers between conditions, identifying master transcription factor networks, or predicting BET-inhibitor responsiveness.

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Detect and adjust for horizontal pleiotropy in two-sample Mendelian randomization by distinguishing uncorrelated (UHP) from correlated (CHP) pleiotropy and choosing among Egger, MR-PRESSO, MR-RAPS, CAUSE, LHC-MR, LCV, MR-Clust, MR-Mix, and contamination-mixture methods. Use when validating an MR causal claim, running the STROBE-MR sensitivity battery, suspecting a shared heritable confounder, working under weak-instrument or polygenic-exposure regimes, or reconciling discordant estimates across robust methods.

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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 ADMET properties using ADMETlab 3.0 (119 endpoints with uncertainty), ADMET-AI, DeepChem MolNet, and chemprop D-MPNN with explicit handling of OECD QSAR principles, applicability domain assessment, calibration, hERG/CYP/AMES gold-standard endpoints, and PAINS / Lipinski / Ro5 / Veber / BBB druglikeness filters. Use when filtering compounds for drug-likeness, prioritizing leads by predicted safety, or building an in-house ADMET QSAR model.

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Reads, validates, and prepares CDISC SDTM and ADaM clinical trial data for analysis. Covers SDTM domain joins (DM, AE, EX, VS, LB, DS), ADaM architecture (ADSL, BDS, OCCDS, ADTTE) with traceability, treatment-emergent AE conventions, baseline derivation, SUPPQUAL/NSV handling, Define-XML 2.1, and Pinnacle 21 / CORE validation. Use when working with clinical trial datasets in CDISC SDTM/ADaM format, preparing analysis-ready data, or validating for regulatory submission.

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Designs adaptive clinical trials including group-sequential (O'Brien-Fleming, Pocock, Lan-DeMets spending), sample-size re-estimation (blinded Friede-Kieser, unblinded Cui-Hung-Wang, Mehta-Pocock promising zone), seamless Phase 2/3 with treatment-arm selection, population enrichment, and response-adaptive randomisation. Covers FDA 2019 Final Adaptive Designs Guidance, FDA 2022 Master Protocols, and ICH E20 Step 2b/3 draft (June 2025, NOT final). Use when planning interim analyses, sample-size re-estimation, or master/platform-trial designs.

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Create and use BAI/CSI indices for BAM/CRAM files using samtools and pysam. Use when enabling random access to alignment files or fetching specific genomic regions.

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Analyzes differential transcript usage (DTU) and isoform switches with functional consequence prediction (NMD via 50nt rule, ORF disruption, protein domain loss/gain, signal peptide changes, IDR alterations, coding-potential shifts). Tools include IsoformSwitchAnalyzeR v2 (auto-selects satuRn for >5 reps else DEXSeq), the manual DRIMSeq -> DEXSeq/satuRn -> stageR DTU pipeline, and fishpond/swish for inferential-uncertainty-aware DTE. Distinguishes DTU from DGE and DTE; integrates external annotators (CPC2, Pfam, SignalP, IUPred2A or DeepTMHMM). Use when investigating how splicing differences alter protein function or trigger NMD-mediated degradation.

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Live SEO data via DataForSEO MCP server: SERP analysis, keyword research (volume, difficulty, intent, trends), backlink profiles, on-page analysis, competitor and content analysis, business listings, AI visibility (LLM mention tracking), and domain analytics. Requires DataForSEO extension installed. Use when user says "dataforseo", "live SERP", "keyword volume", "backlink data", "AI visibility check", or "real search data".

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Ahrefs API analyst (extension). Reads referring domains, backlinks, organic keywords, and content explorer data via the tested @ahrefs/mcp@0.0.11 server. Pairs with seo-backlinks for multi-source confidence weighting.

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Printing and PDF export for AI response blocks and messages via @ai-matrx/print. Use when adding a print button or BlockPrinter to a render block, wiring PrintOptionsDialog/usePrintOptions, captureBlockElement, or useDomCapturePrint, or when a print window shows no images or a print fails silently.

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Relocating a live, still-used table to another Postgres schema with every reference intact. Use when asked to move or rehome a table into a schema, or to pull a table out of public into a domain schema. NOT for retiring a table (use db-deprecate-table).

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Create algorithmic art using p5.js with seeded randomness and interactive parameter exploration. Use when users request generative art, algorithmic art, flow fields, or particle systems. Create original works rather than copying existing artists.

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Elite UX/UI & Advanced GSAP Motion Engineer. Enforces Python-driven true randomization for layout variance, strict AIDA page structure, wide editorial typography (bans 6-line wraps), gapless bento grids, strict GSAP ScrollTriggers (pinning, stacking, scrubbing), inline micro-images, and massive section spacing.

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Elite frontend image-direction skill for generating premium, conversion-aware website design references. CRITICAL OUTPUT RULE — generate ONE separate horizontal image FOR EVERY section. A landing page with 8 sections produces 8 images. Never compress multiple sections into one image. Enforces composition variety (not always left-text / right-image), background-image freedom, varied CTAs, varied hero scales (giant / mid / mini minimalist), narrative concept spine, second-read moments, and a single consistent palette across all images. Optimized for landing pages, marketing sites, and product comps that developers or coding models can accurately recreate.

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Convex is the backend agents get right on the first try: an all-TypeScript reactive platform where the database, server functions, scheduling, file storage, auth, and realtime sync are one type-safe system, every function is a transaction, and `tsc` catches most mistakes before deploy. Ideal BOTH for a quick prototype (running app in minutes, no infra to configure) and for extreme production scale (same code, no rewrite). Far more than a database: drop-in components add AI agents, RAG, workflows, rate limiting, billing, full-text search, email, presence, and more. Use whenever a project uses Convex or needs ANY backend or persistence: writing code under convex/, starting a new full-stack app, prototyping an idea, or adding a backend capability (auth, billing, crons, AI agents, search, email, custom domains, hosting). Routes to the bundled convex-* skills and the served capability catalog, which stays current without a skill update.

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DDD architecture knowledge base. Provides patterns, antipatterns, and PHP-specific guidelines for Domain-Driven Design audits.

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Generates Application Use Cases for PHP 8.5. Creates orchestration services that coordinate domain objects, handle transactions, and dispatch events. Includes unit tests.

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Analyzes PHP code for immutability violations. Checks Value Objects, Events, DTOs for readonly properties, no setters, final classes, and wither patterns. Ensures domain objects maintain invariants.

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Generates DDD Factory for PHP 8.5. Creates factories for complex domain object instantiation with validation and encapsulated creation logic. Includes unit tests.

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