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Sort alignment files by coordinate or read name using samtools and pysam. Use when preparing BAM files for indexing, variant calling, or paired-end analysis.

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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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Creates sashimi-style plots showing RNA-seq read coverage and splice junction counts using ggsashimi (general-purpose, condition-grouped overlays), rmats2sashimiplot (rMATS-output-aware), MAJIQ-VOILA (LSV posteriors interactive HTML), leafviz (leafcutter clusters Shiny), Jutils (tool-agnostic heatmaps and sashimi for rMATS/leafcutter/SUPPA2/MAJIQ output), or pyGenomeTracks (multi-track publication figures). Tool choice depends on the upstream differential-splicing tool's output format and the publication vs interactive use case. Use when visualizing specific splicing events, validating differential splicing calls, or producing publication-quality figures.

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Generate consensus sequences and manage reference files using samtools. Use when creating consensus from alignments, indexing references, or creating sequence dictionaries.

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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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Detects differential alternative splicing between conditions using rMATS-turbo (binomial LRT on junction counts), leafcutter (Dirichlet-multinomial GLM on intron clusters), MAJIQ V3 deltapsi/HET (Bayesian posterior on LSVs), SUPPA2 (empirical-null on TPM-derived PSI), or Shiba (junction-imbalance-corrected, 2025 SOTA at low coverage). Reports FDR-corrected significance and delta PSI effect sizes. Tools differ in statistical model, annotation dependence, calibration regime, and replicate-count requirements. Use when comparing splicing patterns between treatment groups, tissues, or disease states.

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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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Perform pairwise sequence alignment using Biopython Bio.Align.PairwiseAligner. Use when comparing two sequences, finding optimal alignments, scoring similarity, and identifying local or global matches between DNA, RNA, or protein sequences.

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Perform multiple sequence alignment using MAFFT, MUSCLE5, ClustalOmega, or T-Coffee. Guides tool and algorithm selection based on dataset size, sequence divergence, and downstream application. Use when aligning three or more homologous sequences for phylogenetics, conservation analysis, or evolutionary studies.

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Read, write, and convert multiple sequence alignment files using Biopython Bio.AlignIO. Supports Clustal, PHYLIP, Stockholm, FASTA, Nexus, and other alignment formats for phylogenetics and conservation analysis. Use when reading, writing, or converting alignment file formats.

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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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Use this skill when a driver needs to extend the 14-hour duty window using the 16-hour exception under § 395.1(o). Covers eligibility, frequency limits (once per 7 days), return-to-terminal requirement, and documentation.

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Use this skill when the user asks about driver fitness-for-duty programs — pre-trip readiness assessment, recognizing impairment from drugs/alcohol/medication/fatigue/mental health, refusing assignments when unfit, supervisor training on fitness assessment, FMCSA recommendations on duty status determination, and how to handle a driver who appears unfit. Reference 49 CFR 392.3 + 392.4.

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Use when a carrier asks how to calculate cost-per-mile (CPM) at the fleet, truck, lane, or driver level — separating fixed vs variable costs, allocating overhead, accounting for empty miles, and using CPM to negotiate rates, build pricing tiers, or evaluate lane profitability.

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Principled action selection for autonomous agents using Expected Free Energy (EFE) under the Active Inference framework. Each candidate action is scored as G(n) = w_prag * (-E[p_n] * damping) + w_epist * (-Var[p_n] * novelty(n)), where agent beliefs are maintained as per-node Beta distributions and updated via Bayesian observation. Selection is a softmax over -gamma * G, making exploration an automatic consequence of uncertainty rather than a hardcoded epsilon. Precision weights w_prag and w_epist self-adapt via surprise history, shifting the agent between exploitation and exploration regimes without any manually tuned schedule.

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Interpret and design bounded FIPA communicative-act exchanges using XC00037H semantics while keeping delivery, authority, and external effects separate. NOT for proving delivery, task authorization, or external effect completion.

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Decompose DAGs into execution chains using width bounds, stratification, virtual nodes, and matching. Use when minimizing workflow lanes in dependency graphs. NOT for cyclic graphs, generic scheduling, or one-off queries with no preprocessing payoff.

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Expert data engineer for ETL/ELT pipelines, streaming, data warehousing. Activate on: data pipeline, ETL, ELT, data warehouse, Spark, Kafka, Airflow, dbt, data modeling, star schema, streaming data, batch processing, data quality. NOT for: API design (use api-architect), ML training (use ML skills), dashboards (use design skills).

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Domain-Driven Design methodology using bounded contexts, ubiquitous language, and strategic/tactical patterns

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Master of text-based visual communication using ASCII art, Unicode box-drawing, and structured diagram notation. Creates clear, maintainable diagrams for systems, processes, hierarchies, relationships, and psychological structures. Proactively generates diagrams to enhance understanding. Activate on visualization needs, system architecture, process flows, psychological mapping, or when complex concepts would benefit from visual representation. NOT for photo editing, vector graphics, or GUI-based design tools.

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Executes DAG waves with controlled parallelism using the Task tool. Manages concurrent agent spawning, resource limits, and execution coordination. Activate on 'execute dag', 'parallel execution', 'concurrent tasks', 'run workflow', 'spawn agents'. NOT for scheduling (use dag-task-scheduler) or building DAGs (use dag-graph-builder).

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Matches natural language task descriptions to appropriate skills using semantic similarity. Handles fuzzy matching, intent extraction, and capability alignment. Activate on 'find skill', 'match task', 'semantic search', 'skill lookup', 'what skill for'. NOT for ranking matches (use dag-capability-ranker) or skill catalog (use dag-skill-registry).

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Analyze undirected cycle structure within a valid DAG using the source paper's orientation and contraction method. Use for cycle-basis analysis with explicit graph and reduction choices. NOT for directed feedback loops, workflow deadlocks, or runtime resilience claims.

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Matches natural language task descriptions to appropriate skills using semantic similarity, ranks candidates by fit and performance history, and maintains the skill catalog. Use when assigning skills to DAG nodes, searching for the right skill for a task, ranking competing skills, or browsing the skill catalog. Activate on "find skill", "match skill", "which skill", "skill for this task", "skill catalog", "rank skills", "best skill". NOT for executing DAGs (use dag-runtime), creating skills (use skill-architect), or grading skills (use skill-grader).

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。