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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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Profiles RNA-binding protein targets without antibody or UV crosslinking using STAMP (APOBEC1-RBP fusion, C-to-U editing), scSTAMP (single-cell), TRIBE/HyperTRIBE (ADAR-RBP, A-to-I editing), DART-seq (APOBEC1-YTH for m6A), or Bullseye/SAILOR edit-site detection pipelines. Use when antibody is unavailable or specificity is doubtful, when single-cell RBP profiling is needed (scSTAMP), or when in vivo RBP profiling without UV is preferred.

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Analyzes chemical libraries by scaffold using Bemis-Murcko scaffolds, generic frameworks, cyclic skeletons, matched molecular pair (MMP) analysis via mmpdb, R-group decomposition, Free-Wilson analysis, scaffold hopping, and chemotype-aware ML train/test splits. Use when identifying chemotype clusters in a library, deriving SAR transformation rules, decomposing series into R-groups, performing scaffold-balanced QSAR splits, or planning analog campaigns.

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Normalizes ChIP-seq data using exogenous spike-in (ChIP-Rx with Drosophila chromatin per Orlando 2014 / Egan 2016; E. coli carryover for CUT&RUN/CUT&Tag). Distinguishes RRPM from Rx-Input scaling, integrates with DiffBind / DESeq2 / edgeR / csaw via sizeFactors and DiffBind library-size vectors, and applies the Patel et al 2024 *Nat Biotechnol* review's failure-mode framework to validate that normalization is correctly applied at the read level (not peak counts). Use when global signal shifts are expected (HDACi, BETi, EZH2i, dosage, target knockdown), when ChIPseqSpikeInFree detects post-hoc shifts, or when validating internal-control regions before publication.

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Performs retrosynthetic planning using AiZynthFinder (MCTS, template-based), Chemformer (template-free transformer), ASKCOS, and emerging RetroSynFormer with explicit handling of route scoring, building-block availability (eMolecules, Enamine, Mcule), forward prediction validation (Molecular Transformer), and disconnection-aware multi-objective search (MO-MCTS). Use when assessing synthetic feasibility of generated or selected molecules, planning multi-step syntheses, building synthesis-aware design pipelines, or screening libraries for retro-route feasibility.

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Enumerates virtual chemical libraries via reaction SMARTS transformations using RDKit and Reaction templates, with explicit handling of atom mapping, template extraction (RDKit reaction mining), product validation, RECAP/BRICS fragmentation, R-group decomposition, matched molecular pair analysis (MMPA), and Free-Wilson analysis. Use when generating combinatorial libraries from building blocks, enumerating analog series, deriving structure-activity rules, or extracting transformations from reaction data.

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Analyzes alternative splicing at single-cell resolution. The first decision is library chemistry — 10X 3' is fundamentally limited (RT primes from poly-A, R2 falls in 3' UTR, <0.1 junction read per cell per AS event). Plate-based full-length methods (Smart-seq3, FLASH-seq, VASA-seq, STORM-seq) and single-cell long-read (MAS-Iso-seq, scISOr-Seq2) are the chemistries that give per-cell isoform structure. Tools include MARVEL (R, Smart-seq integrated), BRIE2 (Bayesian PSI with regulatory features and ELBO_gain test), scQuint (junction-cluster, plate-based; not for 10X), SpliZ (annotation-free Z-score), Psix (graph-smoothness regulated AS), and Sierra (alternative polyadenylation, often confused with AS). Use when analyzing isoform usage in scRNA-seq, identifying cell-type-specific splicing, or determining whether scRNA-seq chemistry supports splicing analysis at all.

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Quantifies alternative splicing as PSI (percent spliced in) from RNA-seq using rMATS-turbo (BAM-based event), SUPPA2 (TPM-based event), MAJIQ V3 (LSV-based Bayesian), leafcutter (annotation-free intron clusters), VAST-TOOLS (cross-species with microexon support), Shiba (junction-imbalance-corrected, 2025 SOTA at low coverage), or IRFinder-S (intron retention coverage-aware). Distinguishes the five canonical event classes (SE, A5SS, A3SS, MXE, RI), special classes (microexons, exitrons, AFE/ALE), intron retention subtypes (canonical RI vs detained introns), and applies effective-length normalization. Use when measuring splice-site usage or isoform inclusion ratios from short-read RNA-seq.

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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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Biopython is a comprehensive set of freely available Python tools for biological computation. It provides functionality for sequence manipulation, file I/O, database access, structural bioinformatics, phylogenetics, and many other bioinformatics tasks.

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A hard-edged writing style contract for timeless, forceful English prose without modern AI tics. Use when users ask for prose or rewrites that must be clean, exact, concrete, and free of AI cadence, filler, or therapeutic tone.

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Auri: assistente de voz inteligente (Alexa + Claude claude-opus-4-20250805). Visao do produto, persona Vitoria Neural, stack AWS, modelo Free/Pro/Business/Enterprise, roadmap 4 fases, GTM, north star WAC e analise competitiva.

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Format Haskell package descriptions and cabal project files with cabal-gild: *.cabal, cabal.project, cabal.project.local, and cabal.project.freeze. Use after editing dependencies or stanzas, when refreshing cabal-gild discover module lists, or when checking cabal file formatting.

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When the user wants to optimize signup, registration, account creation, or trial activation flows. Also use when the user mentions "signup conversions," "registration friction," "signup form optimization," "free trial signup," "reduce signup dropoff," "account creation flow," "people aren't signing up," "signup abandonment," "trial conversion rate," "nobody completes registration," "too many steps to sign up," or "simplify our signup." Use this whenever the user has a signup or registration flow that isn't performing. For post-signup onboarding, see onboarding-cro. For lead capture forms (not account creation), see form-cro.

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Full safety mode: destructive command warnings + directory-scoped edits. Combines /careful (warns before rm -rf, DROP TABLE, force-push, etc.) with /freeze (blocks edits outside a specified directory). Use for maximum safety when touching prod or debugging live systems. Use when asked to "guard mode", "full safety", "lock it down", or "maximum safety". (gstack)

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Elite frontend image-direction skill for generating premium, conversion-aware website design references. CRITICAL OUTPUT RULE — generate ONE separate horizontal image FOR EVERY section. A landing page with 8 sections produces 8 images. Never compress multiple sections into one image. Enforces composition variety (not always left-text / right-image), background-image freedom, varied CTAs, varied hero scales (giant / mid / mini minimalist), narrative concept spine, second-read moments, and a single consistent palette across all images. Optimized for landing pages, marketing sites, and product comps that developers or coding models can accurately recreate.

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Keep responsive shared interactions deterministic and free of duplicated side effects while server authority wins.

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Strip a problem to its irreducible fundamental truths and rebuild the solution from the ground up — free from analogy, convention, and inherited assumptions. Load when the user feels constrained by how something has always been done, when existing solutions feel expensive or inefficient for no good reason, when the user asks to think from first principles, challenge the fundamentals, or rebuild this from scratch. Also triggers on "why does it have to work this way", "what are the actual constraints here", "ignore what everyone else does", or when deep-thinking diagnoses a convention-break frame. Based on Aristotle's first principles method, popularised by Musk and Feynman. Produces genuinely novel solutions by eliminating convention.

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Instrument a shipped product's AI agents with tracing and observability so you can see what they did, why outputs happened, and what each run cost. Plain-language primer plus free-tier-first backend selection (Langfuse, Phoenix, LangSmith, Braintrust) and OpenTelemetry/OpenInference instrumentation. Load when the user asks to add observability, add tracing, instrument my agents, see what my agent is doing in production, set up Langfuse or Phoenix or LangSmith, debug why my agent gave a bad answer, or track LLM cost per request. Also fires when agent-system-architecture or setup-evaluation requires an observability plan for an agent-chain product. NOT for tracing the coding agent itself — that is run-trace. Precondition for runtime-learning-loop.

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。

A hard-edged writing style contract for timeless, forceful English prose without modern AI tics. Use when users ask for prose or rewrites that must be clean, exact, concrete, and free of AI cadence, filler, or therapeutic tone.

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。

Biopython is a comprehensive set of freely available Python tools for biological computation. It provides functionality for sequence manipulation, file I/O, database access, structural bioinformatics, phylogenetics, and many other bioinformatics tasks.

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。

Auri: assistente de voz inteligente (Alexa + Claude claude-opus-4-20250805). Visao do produto, persona Vitoria Neural, stack AWS, modelo Free/Pro/Business/Enterprise, roadmap 4 fases, GTM, north star WAC e analise competitiva.

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Evaluates genome assembly quality across the three orthogonal axes - contiguity (QUAST auN/NG50/NGx, not bare N50), completeness (BUSCO/compleasm gene-space plus Merqury k-mer completeness), and correctness (reference-free Merqury QV, Inspector/CRAQ structural errors, asmgene false-duplication/collapse). Covers why N50 is the most-gamed metric, why QV measured on the polishing reads is circular, distinguishing uncollapsed haplotigs from real WGD, and the EBP/VGP 6.C.Q40 standard. Use when judging whether an assembly is good enough to annotate or publish, comparing assemblers, diagnosing a fragmented or duplicated assembly, or assessing a phased diploid assembly.

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。

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.

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。