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概要と使いどころ
Specify algorithms for Model-Based Design: system specs, architecture specs, implementation plans, test plans. Use when creating specifications for controllers, signal processing, diagnostics, estimators, or other algorithms authored in Simulink, Stateflow, System Composer, or MATLAB Function blocks.
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Specify plant models for closed-loop simulation: system specs, architecture, build plans, validation plans. Use when creating, updating, or reviewing plant model specifications, planning plant model architecture, or planning plant model validation.
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Manages MATLAB projects for Simulink workflows: path management, file registration, labels, source control configuration, and project lifecycle. Use when creating projects, adding models/dictionaries/requirements to projects, configuring labels for automation, fixing broken model references, or setting up source control for Simulink artifacts.
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Register, add, or update existing custom Simulink block libraries and configure block policy and knowledge index. Use when a user wants to register, set up, configure, or add existing .slx library files for agent-assisted model building. Do NOT use when the user wants to create or author a new library from scratch — that requires building-simulink-models.
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Use this skill to run multiple Simulink simulations in parallel with parsim, batchsim, and DesignStudy. TRIGGER when: user asks for parameter sweep, sweeping/varying parameters across simulations, Monte Carlo study, batch simulation, running multiple simulations, parallel simulations, large-scale multiple simulations, any task involving repeated simulations with different parameter values, user mentions having an existing script/function for parameter sweeps, or user wants to migrate from parfor/set_param/for-loop patterns to recommended workflows.
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Configures Simulink simulations non-destructively using SimulationInput objects — parameter overrides without modifying the model, batch sweeps via parsim, custom input signals via Dataset, and simulation data retrieval via logsout. Use when running sim()/parsim() with setVariable, setBlockParameter, setExternalInput, or when performing parameter sweeps and multi-run analysis. Not needed for one-shot simulations without configuration.
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Design stable, compatible public APIs using extend-only design principles. Manage API compatibility, wire compatibility, and versioning for NuGet packages and distributed systems.
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Provides guidance for implementing OpenTelemetry instrumentation in .NET codebases, covering tracing (Activities/Spans), metrics, logs, naming conventions, error handling, performance, SDK setup, resources, context propagation, and API design best practices.
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Guidelines for introducing and using nullable reference types (NRT) and System.Diagnostics.CodeAnalysis nullable attributes in C# / .NET codebases. Covers the nullability model, flow analysis, the null-forgiving operator, API design rules, the full attribute catalog (AllowNull, DisallowNull, MaybeNull, NotNull, NotNullWhen, MaybeNullWhen, NotNullIfNotNull, MemberNotNull, MemberNotNullWhen, DoesNotReturn, DoesNotReturnIf), the C# 14 field keyword, incremental migration of legacy codebases, and a code-generation checklist.
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Design .NET types for performance. Seal classes, use readonly structs, prefer static pure functions, avoid premature enumeration, and choose the right collection types.
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Designs pegRNAs and nicking guides for prime editing (PE) -- choosing the nick/strand, tuning the primer-binding site (PBS) and reverse-transcription template (RTT) as a per-locus panel, selecting the PE system (PE2/PE3/PE3b/PE4/PE5/PEmax/PE7), adding MMR-evading and PAM-disrupting silent edits, appending epegRNA 3' motifs (tevopreQ1/mpknot), and ranking with PRIDICT/DeepPrime. Covers twinPE/PASTE for large insertions and the prime-vs-base-editing decision. Use when designing a scarless point mutation, small insertion/deletion, or any of the 12 base conversions without a double-strand break, when efficiency is low and MMR inhibition or pegRNA stabilization is needed, or when routing a large insertion to an integrase method. Generic guide scoring and base editing are separate skills.
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Predict B-cell and T-cell epitopes for vaccine antigen design and epitope mapping with BepiPred-3.0, DiscoTope-3.0, the IEDB tools, and EL-mode MHC presentation. Encodes the load-bearing asymmetry that T-cell epitope prediction is mature (it reduces to MHC presentation, AUC>0.9) while B-cell prediction is unreliable (linear predictors ~AUC 0.6 because ~90% of real epitopes are conformational) — so structure-based DiscoTope-3.0 on AlphaFold models is the only defensible B-cell path, propensity scales are obsolete, and NetChop is largely redundant on EL-trained models. Use when mapping epitopes or selecting vaccine antigens. MHC binding lives in mhc-binding-prediction.
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Designs donor/repair templates for precise CRISPR knock-ins -- choosing the format (ssODN, long-ssDNA/Easi-CRISPR, dsDNA/plasmid, AAV6), sizing homology arms, placing the cut within ~10 bp of the edit, and adding a mandatory codon-checked blocking (PAM/seed) mutation so the edited allele is not re-cut. Frames the HDR-vs-NHEJ-vs-MMEJ pathway competition, the MMEJ (PITCh) and homology-independent (HITI/HMEJ) alternatives for post-mitotic cells, ssODN strand/asymmetry choice, phosphorothioate end-protection, and ranked HDR enhancers. Use when designing a donor for a point mutation, epitope/fluorophore tag, allele replacement, or knock-in, or when HDR efficiency is low. Guide design and base/prime editing are separate skills.
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Designs and ranks guide RNAs (sgRNAs) for CRISPR-Cas9/Cas12a gene knockout by scanning a target for PAM sites (NGG SpCas9, NNGRRT SaCas9, TTTV Cas12a, NG SpCas9-NG, near-PAMless SpRY), enumerating candidate spacers, applying hard filters (Pol-III TTTT terminator, 5' G, GC), ranking on-target activity with the context-appropriate model (Rule Set 2/Azimuth for U6/lentiviral, CRISPRscan for T7/embryo, DeepHF for high-fidelity variants, DeepCpf1 for Cas12a), and predicting the indel/frameshift outcome (Bae out-of-frame score, inDelphi, FORECasT, Lindel). Use when selecting sgRNAs to knock out a gene, choosing a nuclease/PAM for a constrained locus, picking which exon to target, or shortlisting guides before an off-target check. Off-target specificity, base/prime editing, and HDR donors are separate skills.
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Designs cytosine (CBE, C-to-T) and adenine (ABE, A-to-G) base-editor guides by positioning the target base at the activity-peak of the editing window (protospacer positions ~5-7, PAM-distal numbering), minimizing bystander edits for product purity, reading dinucleotide context (APOBEC1 TC favored / GC disfavored), and selecting the editor variant (BE4max, ABEmax, ABE8e, YE1/SECURE, TadCBE, CGBE, SpG/SpRY-BE). Covers knockout by premature stop (CRISPR-STOP/iSTOP) and splice-site disruption, the three off-target classes (Cas-dependent, Cas-independent DNA, RNA), outcome prediction (BE-Hive/DeepBE), and the base-vs-prime-vs-HDR decision. Use when installing a transition mutation without a double-strand break, knocking out a gene without indels, or choosing CBE vs ABE. Generic guide scoring, prime editing, and HDR donors are separate skills.
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Aligns sample metadata with count matrices and constructs design matrices for downstream DE, handling the alphabetical-reference-level trap (relevel BEFORE DESeq), LRT reduced-model rules, the interaction-term resultsNames trap, continuous-covariate scaling and splines, repeated measures via duplicateCorrelation or dream, high-cardinality categorical pseudo-singular designs, sample swap detection via XIST/RPS4Y1 expression and somalier/NGSCheckMate genotypes, SABV (sex-as-biological-variable) mandate, Simpson's-paradox collapsing of technical replicates, and the `~ 0 + group` parameterization for clean contrasts. Use when building a design matrix, troubleshooting reversed fold-change direction, encoding paired or repeated-measures designs, detecting sample swaps, deciding sex-as-covariate, or aggregating technical replicates.
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Structures biological experiments so inference is valid by construction, covering Fisher's principles (randomization, replication, local control), the experimental-vs-observational unit distinction and pseudoreplication (Hurlbert 1984; Lazic 2018), randomization mechanics (complete, restricted, stratified, rerandomization, run-order), blocking layouts (randomized complete block, Latin square, incomplete block), factorial designs and interactions, and the split-plot/nested error strata hidden inside multi-batch genomics. Use when deciding the experimental unit and what counts as a replicate, planning randomization and run order, choosing a blocked/factorial/split-plot/nested layout, avoiding pseudoreplication in cell-culture or animal studies, or specifying the random-effects structure of the analysis model. For assigning samples to sequencing batches/lanes/plates and batch-effect correction see experimental-design/batch-design; for regulated clinical-trial randomization see clinical-biostatistics.
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Estimates the minimum biological replicates (or cells/events) for a target power at a target FDR in genomics experiments using ssizeRNA, PROPER, powsimR for scRNA-seq, and pilot-data dispersion estimation from DESeq2/edgeR. Covers the biological-versus-technical replication distinction (technical replicates do not add degrees of freedom for biological inference), replicate-number-versus-sequencing-depth budgeting, scRNA-seq sample-versus-cell allocation under a pseudobulk model, and the critique that "n=3" is a publication convention rather than a power calculation. Use when budgeting a sequencing experiment, writing the sample-size justification in a grant, estimating replicates from pilot data, allocating a fixed budget between samples and depth, or planning scRNA-seq cohort size. For clinical-trial sample size see clinical-biostatistics/power-and-sample-size; for the power-given-n direction see experimental-design/power-analysis.
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Designs genomics experiments so technical nuisance variation (batch, lane, plate, flow cell, operator, reagent lot, processing day) is balanced against the biological variable of interest and therefore estimable rather than confounded, using constrained sample-to-batch assignment (designit, OSAT), the confounder/mediator/collider distinction, and the principle that no post-hoc correction recovers a fully confounded design. Covers detecting hidden batches with surrogate variable analysis, a decision table for downstream correction (ComBat-seq, RUVSeq, SVA) whose execution is deferred to differential-expression/batch-correction, and reproducibility metadata. Use when assigning samples to sequencing batches/lanes/plates, avoiding batch-condition confounding, deciding whether a design is salvageable by correction, choosing a correction method, or estimating the number of hidden batches. For the experimental unit, randomization, and blocking concepts see experimental-design/randomization-blocking.
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Calculates statistical power for high-dimensional genomics experiments (bulk RNA-seq, scRNA-seq, ATAC-seq, ChIP-seq, methylation, proteomics) under negative-binomial count models using RNASeqPower, PROPER, and simulation via powsimR, distinguishing per-gene from marginal (transcriptome-wide) power, the role of mean expression and dispersion, and the sequencing-depth-versus-replicate tradeoff. Covers simulation as the honest default for overdispersed counts, FDR-aware average power versus single-test power, observed/post-hoc power as an anti-pattern, and the winner's-curse / Type-S / Type-M consequences of underpowering. Use when planning replicate number for a sequencing experiment, deciding whether to add depth or samples, choosing closed-form versus simulation power, estimating power from pilot dispersions, or justifying replication in a grant. For clinical-trial power see clinical-biostatistics/power-and-sample-size; for the inverse sample-size question see experimental-design/sample-size.
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Analyzes single-cell pooled CRISPR screens (Perturb-seq, CROP-seq, Perturb-CITE-seq, ECCITE-seq, multiome) where each cell carries an sgRNA and a scRNA-seq / surface-protein / chromatin readout. Covers experimental design (direct-capture Perturb-seq Dixit 2016 vs CROP-seq 3'UTR-barcoded Datlinger 2017 vs ECCITE-seq vs Multiome), MOI for sgRNA assignment, escaper-cell filtering (Mixscape, Papalexi 2021), SCEPTRE NB GLM + permutation for low-MOI (Barry 2024 Genome Biol 25:124), the Pertpy framework, factor decomposition, genome-scale Perturb-seq (Replogle 2022 Cell, 2.5M cells), and per-perturbation single-cell DE. Use when running a single-cell CRISPR screen, choosing direct-capture vs CROP-seq architecture, filtering escaper cells, performing single-cell DE, integrating Perturb-seq with pathway analysis, scaling to GW CRISPRi via Replogle protocol, or analyzing multi-omics screens.
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Designs pooled sgRNA libraries for CRISPR knockout, interference (CRISPRi), activation (CRISPRa), Cas12a multiplex, base-editor, and prime-editor screens. Covers on-target scoring (Rule Set 2, Azimuth, DeepSpCas9, CRISPRon), off-target scoring (CFD, MIT), TSS-relative positioning for CRISPRi/a (Horlbeck, Dolcetto, Calabrese), PAM-variant chemistries, control-guide composition, oligo cloning architecture, and library QC. Use when choosing a genome-wide library (GeCKOv2 vs Avana vs Brunello vs TKOv3 vs Inzolia), designing a focused or paralog-focused custom library, picking CRISPRi vs CRISPRa TSS windows, deciding control-guide proportions, or diagnosing library skew and dropout in a freshly cloned pool.
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Designs and analyzes in vivo CRISPR screens in animal tumor models, organoids, and immune-cell adoptive transfers. Covers bottleneck math (250x cells/sgRNA requires ~25M cells implanted; impossible for most syngeneic models, forcing focused libraries), focused library design (Manguso 2017 Nature 547:413 immune screen; Chen 2015 tumor screens), CRISPR-StAR intrinsic-control screening (Uijttewaal 2025 Nat Biotechnol 43:1848), clonal-dynamics-limited detection, tumor-explant DNA recovery, syngeneic vs xenograft vs PDX considerations, and the relationship to downstream MAGeCK / drugZ analysis. Use when designing in vivo CRISPR screens for tumor / immune / metastasis biology, choosing focused vs genome-wide for animal models, addressing bottleneck-induced clonal collapse, picking the syngeneic / xenograft / PDX model, integrating in vivo with in vitro results, or applying CRISPR-StAR for animal experiments.
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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 for predicting per-pegRNA editing efficiency, pegRNA architecture (spacer + scaffold + PBS + RTT), PE2/PE3/PE3b/PEmax variants, MOSAIC in situ saturation mutagenesis, the PRIME pooled-screen methodology (Ren 2023; ~3,699 ClinVar variant screens), chromatin context as a major locus-level 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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