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Comprehensive backend development guide for Langfuse's Next.js 14/tRPC/Express/TypeScript monorepo. Use when creating tRPC routers, public API endpoints, BullMQ queue processors, services, or working with tRPC procedures, Next.js API routes, Prisma database access, ClickHouse analytics queries, Redis queues, OpenTelemetry instrumentation, Zod v4 validation, env.mjs configuration, tenant isolation patterns, or async patterns. Covers layered architecture (tRPC procedures → services, queue processors → services), dual database system (PostgreSQL + ClickHouse), projectId filtering for multi-tenant isolation, traceException error handling, observability patterns, and testing strategies (Jest for web, vitest for worker).

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Create and manage database migrations with reversible changes, proper naming conventions, and zero-downtime deployment strategies. Use this skill when creating database migration files, modifying schema, adding or removing tables/columns, managing indexes, or handling data migrations. Apply when working with migration files (e.g., db/migrate/, migrations/, alembic/, sequelize migrations), schema changes, database versioning, rollback implementations, or when you need to ensure backwards compatibility during deployments. Use for any task involving database structure changes, index creation, constraint modifications, or data transformation scripts.

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Define database models with clear naming, appropriate data types, constraints, relationships, and validation at multiple layers. Use this skill when creating or modifying database model files, ORM classes, schema definitions, or data model relationships. Apply when working with model files (e.g., models.py, models/, ActiveRecord classes, Prisma schema, Sequelize models), defining table structures, setting up foreign keys and relationships, configuring cascade behaviors, implementing model validations, adding timestamps, or working with database constraints (NOT NULL, UNIQUE, foreign keys). Use for any task involving data integrity enforcement, relationship definitions, or model-level data validation.

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Align protein structures using Foldseek 3Di, TM-align, US-align, DALI, or Foldmason for structural MSA. Predict, score, and superpose backbone coordinates when sequence identity is below the twilight zone or remote-homology detection is required. Use when sequence MSA fails (<25% identity), when the dark proteome is the target, when AlphaFoldDB / ESM Atlas search is needed, or when structural superposition is the goal.

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Benchling Python SDK and REST API integration for registry entities, inventory, ELN entries, workflows, Benchling Apps, and Data Warehouse queries. Use when automating lab data with benchling-sdk or the v2 API.

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Use this skill when working with Brain Imaging Data Structure (BIDS) datasets: organizing neuroscience and biomedical data (MRI, EEG, MEG, iEEG, PET, microscopy, NIRS, motion capture, EMG, MR spectroscopy, behavioral), querying BIDS layouts, validating compliance, converting DICOM to BIDS, writing metadata sidecars, or creating BIDS derivatives.

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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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Parse and analyze multiple sequence alignments using Biopython. Extract sequences, identify conserved regions, analyze gaps, work with annotations, and manipulate alignment data for downstream analysis. Use when parsing or manipulating multiple sequence alignments.

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Validate alignment quality with insert size distribution, proper pairing rates, GC bias, strand balance, and other post-alignment metrics. Use when verifying alignment data quality before variant calling or quantification.

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Treats a ctDNA assay as a molecule-counting experiment at the Poisson edge and builds its analytical-validation case the measurement-science way. Covers the genome-equivalent currency (~330 haploid copies/ng), the lambda = input_GE x VAF sampling ceiling (lambda>=3 for ~95% detection), the error-suppression ladder (raw NGS ~1e-3 -> single-strand UMI ~1e-4/1e-5 -> duplex <1e-7), the CLSI EP17 LoB/LoD/LoD95/LoQ framework, the per-locus-vs-panel-integrated LoD distinction that lets bespoke MRD reach ppm, contrived/SEQC2 reference standards, and honest LoD reporting conditioned on input mass + consensus depth + replicate detection rate. Use when stating or trusting a sensitivity claim, designing a dilution-series validation, deciding how many genome equivalents are needed at a target VAF, choosing a single-locus vs panel-integrated LoD, or auditing a "detects 0.1% VAF" claim.

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Map nucleosome center positions, occupancy, and fuzziness from ATAC-seq fragment-size patterns using NucleoATAC, ATACseqQC, DANPOS3, or scprinter. Use when characterizing nucleosome organization at promoters and enhancers, calling +1/-1 nucleosomes flanking NFRs, generating V-plots for chromatin structure visualization, or comparing nucleosome positioning between conditions.

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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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Implement authentication and authorization with Better Auth - a framework-agnostic TypeScript authentication framework. Features include email/password authentication with verification, OAuth providers (Google, GitHub, Discord, etc.), two-factor authentication (TOTP, SMS), passkeys/WebAuthn support, session management, role-based access control (RBAC), rate limiting, and database adapters. Use when adding authentication to applications, implementing OAuth flows, setting up 2FA/MFA, managing user sessions, configuring authorization rules, or building secure authentication systems for web applications.

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Search scientific papers via the BGPT MCP server and retrieve structured experimental data — methods, results, conclusions, quality scores, and 25+ metadata fields per paper.

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Search scientific papers and retrieve structured experimental data extracted from full-text studies via the BGPT MCP server. Returns 25+ fields per paper including methods, results, sample sizes, quality scores, and conclusions. Use for literature reviews, evidence synthesis, and finding experimental details not available in abstracts alone.

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Infer cis-regulatory connections (peak-to-peak co-accessibility) from scATAC-seq using Cicero, ArchR getCoAccessibility, or SCENIC+. Use when linking enhancer accessibility to promoter accessibility, identifying enhancer-gene pairs from chromatin alone (without paired RNA), running gene-regulatory inference combining ATAC + RNA, or comparing predicted regulatory contacts against Hi-C/Micro-C ground truth.

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Analyze TF motif accessibility variability across samples or single cells using chromVAR. Use when identifying TF motifs whose accessibility correlates with conditions, computing per-sample motif z-scores after matched background correction, comparing to ArchR / Signac equivalents, or distinguishing motif-accessibility signal from per-site footprinting.

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Run read-only SQL against BigQuery public datasets with local result capture, cost safeguards, and reproducibility outputs.

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Build automated billing systems for recurring payments, invoicing, subscription lifecycle, and dunning management. Use when implementing subscription billing, automating invoicing, or managing recurring payment systems.

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End-to-end binder design using BindCraft hallucination. Use this skill when: (1) Designing protein binders with built-in AF2 validation, (2) Running production-quality binder campaigns, (3) Using different design protocols (fast, default, slow), (4) Need joint backbone and sequence optimization, (5) Want high experimental success rate. For backbone-only generation, use rfdiffusion. For QC thresholds, use protein-qc. For tool selection guidance, use binder-design.

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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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Master defensive Bash programming techniques for production-grade scripts. Use when writing robust shell scripts, CI/CD pipelines, or system utilities requiring fault tolerance and safety.

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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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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.

日本語の概要は準備中です。原文の説明を表示しています。