「tia」の検索結果

Discovers de novo motifs and tests known motif enrichment in ChIP-seq, ATAC-seq, or other peak sequences using HOMER, MEME-ChIP (STREME, CentriMo, TOMTOM, FIMO), monaLisa, and AME. Handles background selection (GC-matched, dinucleotide-shuffled, Markov order-2, peak-flanks), motif databases (JASPAR 2024 CORE PWMs, JASPAR 2026 deep-learning collection, HOCOMOCO v12, HOMER built-in), centrally-enriched motif testing, and differential motif analysis. Use when identifying TF binding motifs in peaks, testing for known TF enrichment, scanning for motif instances, comparing motif content between conditions, or interpreting motifs from deep learning models.

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Builds and applies 3D pharmacophore models using RDKit Pharm3D, the apo2ph4 receptor-based workflow (Heider et al. 2023), Pharmer / Pharmit for search, and PharmacoForge for protein-pocket-conditioned pharmacophore generation (Flynn et al. 2025), covering ligand-based pharmacophores from active-set alignment and receptor-based pharmacophores from binding-pocket geometry. Explicitly handles feature types, geometric tolerances, partial matching, and pharmacophore-based virtual screening. Use when identifying scaffold-hopping candidates, building shape-and-feature search queries, or transferring SAR across chemotypes.

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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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Calculates molecular fingerprints (ECFP/Morgan, FCFP, MACCS, RDKit, AtomPair, TopologicalTorsion, Avalon, MAP4, MHFP6) and physicochemical descriptors (Lipinski, QED, TPSA, Crippen LogP, 3D shape) with explicit choice tables, bit vs count semantics, and partial-charge model selection. Use when featurizing molecules for similarity, QSAR, virtual screening, or ML, or selecting the correct fingerprint for a chemotype-aware task.

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Performs alchemical free-energy calculations including relative binding free energy (RBFE / FEP+) and absolute binding free energy (ABFE) via OpenFE, FEP+, GROMACS, AMBER pmemd, and OpenMM with explicit lambda scheduling, soft-core potentials, MBAR/BAR analysis, cycle-closure validation, and protocol-appropriate enhanced sampling. Compares ML alternatives (Boltz-2 affinity, DeepDock). Use when ranking analogs by binding affinity beyond docking accuracy, performing prospective lead optimization, or validating SAR predictions.

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Estimates bivariate genetic correlation (rg) between traits from GWAS summary statistics or individual-level genotypes using cross-trait LDSC, HDL, LAVA, rho-HESS, GREML-bivariate, Popcorn, and HDL-L. Use when quantifying shared genetic architecture between two traits, screening MR validity before causal inference, distinguishing global from locus-level rg, estimating trans-ancestry rg, separating partial from full causation via LCV gcp, or producing a STROBE-MR-compliant cross-trait sensitivity battery. Cross-trait LDSC intercept absorbs sample overlap and is NOT a bias; HDL is biased under sample overlap above ~5%. High rg between exposure and outcome motivates CHP-aware MR sensitivity (CAUSE, LHC-MR).

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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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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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Decompose total effects into direct and indirect paths through mediators using mediation, CMAverse 4-way, HIMA/HIMA2 high-dimensional, BAMA, two-step / MVMR mediation, or double-ML medDML. Use when testing whether a molecular phenotype (expression, methylation, protein) mediates a treatment-outcome relationship, decomposing exposure-mediator interaction via VanderWeele 4-way, screening high-dimensional EWAS mediators, or running MR-based mediation when sequential ignorability is implausible.

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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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Detect transcription factor binding footprints in ATAC-seq using TOBIAS, HINT-ATAC, Wellington, or scprinter. Use when identifying bound TF sites within accessible regions, correcting Tn5 insertion bias before footprinting, choosing between cleavage-based and aggregate-based footprinters, or comparing differential TF activity between conditions.

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Use when the user mentions security review, App Store submission prep, Privacy Manifest requirements, hardcoded credentials, or sensitive data storage.

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Use when storing credentials securely, encrypting data, implementing passkeys, securing AI/agentic features against prompt injection, code signing, or managing certificates and provisioning profiles.

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Workflow skill for KiCAD PCB layout and routing via MCP tools. Triggers on: "layout the board", "route traces", "PCB", "place footprints", "copper pour", "board outline", "differential pair", "board setup", "track width", "via", "zone", "design rules", "stackup", "silkscreen".

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Use when working with iOS/macOS Keychain Services (SecItem queries, kSecClass, OSStatus errors), biometric authentication (LAContext, Face ID, Touch ID), CryptoKit (AES-GCM, ChaChaPoly, ECDSA, ECDH, HPKE, ML-KEM), Secure Enclave, secure credential storage (OAuth tokens, API keys), certificate pinning (SecTrust, SPKI), keychain sharing across apps/extensions, migrating secrets from UserDefaults or plists, or OWASP MASVS/MASTG mobile compliance on Apple platforms.

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Builds multiplayer spatial board games using TabletopKit on visionOS. Use when creating tabletop game experiences with boards, pieces, cards, or dice; managing seats, turns, equipment state, TabletopAction flows, or TabletopInteraction delegates; synchronizing gameplay through FaceTime Group Activities; rendering with RealityKit; or implementing snapping, tosses, and physics on a virtual table surface.

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Implement, review, or improve data visualizations using Swift Charts. Use when building bar, line, area, point, pie, donut, or iOS 26 3D charts; when adding chart selection, scrolling, annotations, axes, scales, legends, or foregroundStyle grouping; when plotting functions with BarPlot, LinePlot, AreaPlot, PointPlot, Chart3D, or SurfacePlot; or when creating heat maps, Gantt charts, grouped bars, sparklines, threshold lines, or spatial visualizations.

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Apply modern Swift language patterns and idioms for non-concurrency, non-SwiftUI code. Covers if/switch expressions (Swift 5.9+), typed throws (Swift 6+), result builders, property wrappers, opaque and existential types (some vs any), guard patterns, Never type, Regex builders (Swift 5.7+), basic Codable shaping (CodingKeys, custom decoding, nested containers), modern collection APIs (count(where:), contains(where:), replacing()), basic FormatStyle usage, and string interpolation patterns. Use when writing core Swift code involving generics, protocols, enums, closures, or modern language features; route deep Codable to swift-codable, detailed formatting/localization to swift-formatstyle, and API naming to swift-api-design-guidelines.

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Build and audit SwiftUI, UIKit, and AppKit accessibility for VoiceOver, Voice Control, Switch Control, Full Keyboard Access, Dynamic Type, focus restoration, labels/traits/actions, traversal, custom rotors, NSAccessibility, XCTest checks, adaptive system preferences, and App Store accessibility declarations. Use when implementing accessible UI, fixing an accessibility audit, testing assistive-technology behavior, or substantiating App Store Accessibility Nutrition Labels.

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Support automatic audio switching for paired third-party Bluetooth headphones or earbuds with AudioAccessoryKit. Use when a companion app registers an audio accessory, an app extension reports worn/removed placement or connected source-device changes, or AccessoryControlDevice capabilities and errors need handling. Do not use for general AVAudioSession routing, Bluetooth transport, or initial accessory pairing.

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This skill should be used when the user asks to "set up paper search", reports "paper-search command not found", wants to "replace paper search MCP", or needs help with paper search credentials.

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Manages MongoDB Atlas Stream Processing (ASP) workflows. Handles workspace provisioning, data source/sink connections, processor lifecycle operations, debugging diagnostics, and tier sizing. Supports Kafka, Atlas clusters, S3, HTTPS, and Lambda integrations for streaming data workloads and event processing. NOT for general MongoDB queries or Atlas cluster management. Requires MongoDB MCP Server with Atlas API credentials.

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Optimize MongoDB client connection configuration (pools, timeouts, patterns) for any supported driver language. Use this skill when working/updating/reviewing on functions that instantiate or configure a MongoDB client (eg, when calling `connect()`), configuring connection pools, troubleshooting connection errors (ECONNREFUSED, timeouts, pool exhaustion), optimizing performance issues related to connections. This includes scenarios like building serverless functions with MongoDB, creating API endpoints that use MongoDB, optimizing high-traffic MongoDB applications, creating long-running tasks and concurrency, or debugging connection-related failures.

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Guide users through configuring key MongoDB MCP server options. Use this skill when a user has the MongoDB MCP server installed but hasn't configured the required environment variables, or when they ask about connecting to MongoDB/Atlas and don't have the credentials set up.

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