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Validates docked / generated protein-ligand poses using PoseBusters physical-validity tests, strain energy quantification, geometric checks (planarity, vdW overlap, bond/angle distortion), and pose-energy reasonableness. Filters AI-docking outputs (DiffDock, EquiBind, NeuralPLexer) where ~50% of poses fail physical-validity tests. Use when QC-ing docking results, comparing classical vs ML docking outputs, or filtering pose lists before SAR analysis.

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Maps GWAS-implicated loci to candidate effector (causal) genes by integrating variant-to-gene (V2G) features via Open Targets L2G (Mountjoy 2021), MAGMA gene-based association (de Leeuw 2015), FUMA SNP2GENE, cS2G combined SNP-to-gene scores (Gazal 2022), Polygenic Priority Scores (PoPS, Weeks 2023), FLAMES, INQUISIT, DEPICT, and enhancer-gene predictors (ABC, ENCODE-rE2G). Use when narrowing a GWAS lead locus to a candidate causal gene, picking between proximity, eQTL-based, and similarity-based prioritizers, integrating multi-evidence streams (fine-mapping, colocalization, ABC enhancer-gene, distance, chromatin), reconciling discordant L2G vs PoPS calls, prioritizing tissue-specific eQTL evidence, or triangulating across at least three independent lines of evidence for a publication-grade effector-gene nomination.

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Calls ChIP-seq peaks with MACS3, MACS2, HOMER, or SPP across narrow (TF) and broad (histone) modes. Handles input control matching, fragment-size modeling vs --nomodel, effective genome size, ENCODE-style IDR vs naive overlap, hyper-ChIPable artifacts, and aligner-specific shifts. Use when calling peaks from ChIP-seq alignments, choosing between narrow vs broad mode for a histone mark, deciding model vs nomodel for low-depth data, applying ENCODE pseudoreplicate IDR, or reconciling MACS vs HOMER vs SPP results.

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Predicts whether a DNA variant alters mRNA splicing using sequence-based deep-learning tools — SpliceAI (10kb context dilated CNN, clinical default), Pangolin (multi-tissue), MMSplice (modular per-region CNN with calibrated ΔPSI), SpliceTransformer/TrASPr (tissue-aware transformers), SpliceVault (empirical 300K-RNA lookup of likely mis-splicing outcomes), CADD-Splice (composite score). Applies the ClinGen SVI 2023 framework for ACMG/AMP variant interpretation (PVS1, PP3, BP4 evidence codes), HGVS splicing nomenclature (c.123+1G>A, c.123-3T>G, r.spl?), extended-window scoring for deep-intronic pseudoexons, tissue-specific predictions, branchpoint variant detection (BPHunter, LaBranchoR), and splice-switching ASO design. Use when interpreting splice impact of clinical variants, prioritizing VUS, identifying deep-intronic pathogenic variants, or designing ASOs.

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Call accessible chromatin regions from ATAC-seq BAM files using MACS3, MACS2, Genrich, or HMMRATAC. Use when identifying open chromatin from aligned ATAC-seq, choosing between point-source vs HMM peak callers, applying ENCODE-style pseudoreplicate IDR, removing blacklist regions, or fixing 501bp consensus peaks for downstream differential analysis.

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Process and analyze single-cell ATAC-seq data with Signac, ArchR, SnapATAC2, or Cell Ranger ATAC. Use when handling 10X scATAC or 10X Multiome (paired RNA+ATAC) data, performing per-cell QC, choosing between ArchR/Signac/SnapATAC2 ecosystems, building per-cluster consensus peaksets, integrating with paired scRNA-seq, doublet detection (AMULET vs ArchR vs scDblFinder), or running pseudobulk differential accessibility per cluster.

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Sequence-based deep learning for ATAC-seq using chromBPNet, BPNet, scBasset, or EnFormer. Use when correcting Tn5 bias with neural networks beyond k-mer models, predicting per-base accessibility profiles, scoring in silico variant effects at GWAS or rare-variant SNPs, discovering motifs via DeepLIFT/TF-MoDISco from a trained model, or generating cell-type-specific accessibility predictions for unobserved cell states.

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Detects aberrant splicing in single rare-disease patients vs a control panel using FRASER 2.0 (Bioconductor; Beta-binomial autoencoder on Intron Jaccard Index, default delta cutoff 0.1, q hyperparameter), OUTRIDER (gene-level outlier expression via autoencoder denoising), LeafcutterMD (Dirichlet-multinomial outlier mode of LeafCutter for annotation-free junctions), and DROP (Snakemake pipeline integrating FRASER2 + OUTRIDER + monoallelic expression for clinical diagnostics). The statistical model is fundamentally different from differential splicing — single-sample-vs-cohort outlier detection rather than two-group comparison. Standard tool in EU rare-disease (Solve-RD) and NIH UDN programs. Use when applying RNA-seq to undiagnosed Mendelian disease, validating predicted splice variants in clinical samples, or detecting cryptic splicing in disease tissue.

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Predict enhancer-gene regulatory connections from ATAC-seq using ABC, ENCODE-rE2G, HiChIP, or Cicero. Use when linking distal enhancers to target genes, choosing between contact-aware (ABC, ENCODE-rE2G), accessibility-only (Cicero), and orthogonal (HiChIP H3K27ac, EpiMap) approaches, validating predictions against CRISPRi-FlowFISH gold-standard, or building cell-type-specific regulatory maps for fine-mapping or therapeutic target discovery.

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Connect a customer agent to Coval and complete a small first evaluation with inspected voice or chat results. Use when no usable evaluation exists yet; reuse existing recordings and resources when available.

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Use when the user wants to design, redesign, shape, critique, audit, polish, clarify, distill, harden, optimize, adapt, animate, colorize, extract, or otherwise improve a frontend interface. Covers websites, landing pages, dashboards, product UI, app shells, components, forms, settings, onboarding, and empty states. Handles UX review, visual hierarchy, information architecture, cognitive load, accessibility, performance, responsive behavior, theming, anti-patterns, typography, fonts, spacing, layout, alignment, color, motion, micro-interactions, UX copy, error states, edge cases, i18n, and reusable design systems or tokens. Also use for bland designs that need to become bolder or more delightful, loud designs that should become quieter, live browser iteration on UI elements, or ambitious visual effects that should feel technically extraordinary. Not for backend-only or non-UI tasks.

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Operating guide for the durable Autonomous Work Loop task fleet. Use when adding work to, coordinating, or working an Autonomous Work Loop campaign, or when calling the work_loop MCP tool.

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Scheduled patrol that finds real persistence and error bugs and fixes them. Use when running the system-error repair patrol automation, or when stuck rows, SLA breaches, the system_errors queue, or app_log ERROR rows need a repair rather than a report.

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Discovery batch that grows the Provider Access Launch queue. Use when asked to find more user-connected OAuth, API, API-key, remote MCP, marketplace, or partner-access campaigns for a capability, provider family, MCP/plugin catalog, or competitive gap. NOT for client Local Listings distribution.

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React composition patterns that scale. Use when refactoring components with boolean prop proliferation, building flexible component libraries, or designing reusable APIs. Triggers on tasks involving compound components, render props, context providers, or component architecture. Includes React 19 API changes.

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Use when the user wants to design, redesign, shape, critique, audit, polish, clarify, distill, harden, optimize, adapt, animate, colorize, extract, or otherwise improve a frontend interface. Covers websites, landing pages, dashboards, product UI, app shells, components, forms, settings, onboarding, and empty states. Handles UX review, visual hierarchy, information architecture, cognitive load, accessibility, performance, responsive behavior, theming, anti-patterns, typography, fonts, spacing, layout, alignment, color, motion, micro-interactions, UX copy, error states, edge cases, i18n, and reusable design systems or tokens. Also use for bland designs that need to become bolder or more delightful, loud designs that should become quieter, live browser iteration on UI elements, or ambitious visual effects that should feel technically extraordinary. Not for backend-only or non-UI tasks.

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This skill should be used when agents generate placeholder tokens like "pseudo-", "mock-", "temporary", "TODO", "demo-", or similar incompleteness markers. Detects substitution patterns in agent OUTPUT and triggers mandatory user interview instead of accepting incomplete work. Activates automatically on any output containing forbidden tokens.

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Generates DDD Specification for PHP 8.5. Creates reusable business rule objects for validation, filtering, and querying with composite pattern support. Includes unit tests.

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Generates Object Pool pattern for PHP 8.5. Creates reusable object containers for expensive resources like connections. Includes unit tests.

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Generate A2UI 0.8 protocol compliant UI code. Use when building agent-driven interfaces, generating JSONL messages for surfaceUpdate/dataModelUpdate/beginRendering, creating forms, lists, cards, or any UI components that render across web/mobile/desktop platforms.

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Comprehensive WCAG accessibility auditing with multi-tool testing (axe-core + pa11y + Lighthouse), TRUE PARALLEL execution with Promise.allSettled, graceful degradation, retry with backoff, context-aware remediation, learning integration, and video accessibility. Uses 3-tier browser cascade: Vibium → agent-browser → Playwright+Stealth.

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Strategic amplification mode that reveals blind spots, untapped opportunities, and hidden leverage points in any business strategy, entrepreneurship idea, or creative content project. Cuts through noise to show what others miss.

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[00] TnR ABSOLUTE RIGOR — Systemic Verification Doctrine. Forced cognitive exertion for high-stakes investigations. Mandates absolute deconstruction, mathematical proof chains, and ≥95% derived certainty. Zero-tolerance for heuristics or sentiment-based reasoning. Shortcuts are defined as intentional hallucinations.

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Date and time formatting for OneKey applications. Use when displaying dates, timestamps, or formatting time in UI components. Always use OneKey utilities instead of native JS date methods. Triggers on date, time, timestamp, formatDate, formatTime, toLocaleDateString, toLocaleString, dateUtils, locale, format, display date, show time, datetime, calendar.

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