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Sparse Identification of Nonlinear Dynamics (SINDy) — discover governing equations from time-series data. Builds sparse dynamical system models dx/dt = f(x) from measurements using PySINDy. Use when you have trajectory data and want to find the underlying ODE.

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Implements multiplicity control for confirmatory clinical trials using graphical procedures (Bretz-Maurer-Hommel), gatekeeping (parallel, serial, mixed), Hochberg/Hommel/Holm with PRDS, and the closed-testing principle (Marcus-Peritz-Gabriel; Goeman 2021 admissibility). Covers FDA Multiple Endpoints Final Guidance (October 2022), graphical procedures via R gMCP, primary + key-secondary + subgroup hierarchies, and FWER vs FDR distinction. Use when designing the multiplicity strategy for confirmatory trials with multiple primary or key secondary endpoints.

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Prepares statistical reports for clinical trials following CONSORT 2025, SPIRIT 2025, ICH E9(R1) estimands, and FDA 2023 covariate adjustment guidance. Covers Table 1 generation, analysis populations (ITT/FAS/PP/Safety), the 5 ICH E9(R1) intercurrent-event strategies, MMRM under MAR (mmrm), reference-based MI (rbmi J2R/CR/CIR), Permutt tipping-point sensitivity, and Rubin's-rules vs frequentist variance debate. Use when preparing regulatory submissions, defining estimands, or implementing missing-data sensitivity analyses.

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Meta-analysis / evidence synthesis — pool effect sizes across studies (odds ratios, risk ratios, hazard ratios, mean differences, correlations, GWAS betas) with fixed- or random-effects models, quantify heterogeneity (Q, I², τ²), and build a forest plot. Use when you have results from MULTIPLE studies and need a single pooled estimate, or to synthesize evidence from a systematic review / multiple GWAS / replicated experiments. Handles the error-prone effect-size + standard-error preparation (converting OR/HR/CI, two-group means±SD, proportions, and correlations into the (effect, SE) the pooling step needs).

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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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Build genome-browser-style multi-track figures with pyGenomeTracks (config-driven), Gviz (R), and IGV batch screenshotting. Covers BigWig coverage tracks, BED/peak overlays, gene-model rendering, Hi-C matrix tracks, BedPE link arcs, spike-in-aware normalization, and the bamCoverage --normalizeUsing trap. Use when producing publication figures of genomic loci with stacked aligned tracks (coverage, peaks, genes, interactions) for ChIP-seq, ATAC-seq, RNA-seq, Hi-C, or generic locus visualization.

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Build forest plots (HR, OR, RR, beta-coefficient summaries with CIs) and funnel plots (meta-analysis publication-bias diagnostics) using forestplot, metafor, ggforest, and MendelianRandomization with proper axis-scaling, summary-diamond placement, subgroup nesting, and Egger / trim-and-fill asymmetry tests. Use when summarizing effects across subgroups, trials, or instruments — meta-analysis, Mendelian randomization, subgroup HRs.

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Designs Bayesian clinical trials including Phase I dose-finding (BOIN, CRM, EWOC, mTPI-2), meta-analytic-predictive (MAP) priors with robust mixtures for external data borrowing, EXNEX for basket trials, hierarchical models for safety AE (Berry-Berry), Bayesian platform trials (I-SPY 2, GBM AGILE, REMAP-CAP), and posterior probability stopping rules. Covers FDA Bayesian Devices Guidance (2010), FDA Bayesian Methodology in Drugs Draft (January 2026), BOIN Fit-for-Purpose qualification (December 2021), and Project Optimus dose-optimisation. Use when designing dose-finding studies, platform trials, or sensitivity analyses with informative priors.

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Mendelian randomization (MR) causal inference — does an exposure, risk factor, or biomarker CAUSALLY affect a disease/outcome, using genetic variants as instrumental variables (IEU OpenGWAS / EpiGraphDB MR-EvE). Use this whenever the user asks if X causes Y, whether an observational association is actually causal or just correlation, if a biomarker/trait is a causal risk factor, wants to triangulate epidemiology against genetic evidence, or mentions Mendelian randomization, instrumental-variable analysis, two-sample MR, or genetic causal evidence — even if they never say "MR" (e.g. "is LDL cholesterol actually causal for heart disease?", "does BMI cause type 2 diabetes or just correlate?", "is CRP a causal driver of stroke?"). Covers trait-label resolution, MR effect direction/magnitude, instrument quality (MOE score), method agreement (IVW vs MR-Egger vs weighted median), bidirectional MR for reverse causation, and distinguishing causation from genetic correlation. Not for plain GWAS association lookups (use the GWAS skills) or fitting your own instruments from raw summary statistics.

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Build clustered heatmaps for expression matrices and other features-by-samples data with rigorous distance/linkage/scaling choices, robust color mapping, optimal leaf ordering, and ComplexHeatmap/pheatmap/seaborn rendering. Covers the ward.D vs ward.D2 trap, the row-vs-column scaling decision, multi-track annotations, oncoPrint, and raster rendering for large matrices. Use when visualizing expression patterns across samples or identifying co-regulated clusters.

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Production-ready reinforcement learning algorithms (PPO, SAC, DQN, TD3, DDPG, A2C) with scikit-learn-like API. Use for standard RL experiments, quick prototyping, and well-documented algorithm implementations. Best for single-agent RL with Gymnasium environments. For high-performance parallel training, multi-agent systems, or custom vectorized environments, use pufferlib instead.

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Expert guidance for Fully Sharded Data Parallel training with PyTorch FSDP - parameter sharding, mixed precision, CPU offloading, FSDP2

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High-performance RLHF framework with Ray+vLLM acceleration. Use for PPO, GRPO, RLOO, DPO training of large models (7B-70B+). Built on Ray, vLLM, ZeRO-3. 2× faster than DeepSpeedChat with distributed architecture and GPU resource sharing.

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This skill should be used when working with genomic interval data (BED files) for machine learning tasks. Use for training region embeddings (Region2Vec, BEDspace), single-cell ATAC-seq analysis (scEmbed), building consensus peaks (universes), or any ML-based analysis of genomic regions. Applies to BED file collections, scATAC-seq data, chromatin accessibility datasets, and region-based genomic feature learning.

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Provides guidance for performing causal interventions on PyTorch models using pyvene's declarative intervention framework. Use when conducting causal tracing, activation patching, interchange intervention training, or testing causal hypotheses about model behavior.

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Provides guidance for training and analyzing Sparse Autoencoders (SAEs) using SAELens to decompose neural network activations into interpretable features. Use when discovering interpretable features, analyzing superposition, or studying monosemantic representations in language models.

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Expert guidance for distributed training with DeepSpeed - ZeRO optimization stages, pipeline parallelism, FP16/BF16/FP8, 1-bit Adam, sparse attention

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Build training datasets for LLM specialization from production data, frontier model distillation, and synthetic bootstrapping. Use when formatting production logs into SFT data, distilling from frontier APIs, or preparing data for fine-tuning. Covers JSONL formatting, data quality validation, deduplication, and train/eval splitting.

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Expert guidance for GRPO/RL fine-tuning with TRL for reasoning and task-specific model training

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Provides guidance for interpreting and manipulating neural network internals using nnsight with optional NDIF remote execution. Use when needing to run interpretability experiments on massive models (70B+) without local GPU resources, or when working with any PyTorch architecture.

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High-performance reinforcement learning framework optimized for speed and scale. Use when you need fast parallel training, vectorized environments, multi-agent systems, or integration with game environments (Atari, Procgen, NetHack). Achieves 2-10x speedups over standard implementations. For quick prototyping or standard algorithm implementations with extensive documentation, use stable-baselines3 instead.

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High-level PyTorch framework with Trainer class, automatic distributed training (DDP/FSDP/DeepSpeed), callbacks system, and minimal boilerplate. Scales from laptop to supercomputer with same code. Use when you want clean training loops with built-in best practices.

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State-of-the-art text-to-image generation with Stable Diffusion models via HuggingFace Diffusers. Use when generating images from text prompts, performing image-to-image translation, inpainting, or building custom diffusion pipelines.

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Expert guidance for fine-tuning LLMs with Axolotl - YAML configs, 100+ models, LoRA/QLoRA, DPO/KTO/ORPO/GRPO, multimodal support

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