huang-sh

Diagnostic test / biomarker accuracy — sensitivity, specificity, PPV, NPV, likelihood ratios, accuracy from a 2x2 table; ROC curve, AUC, and the optimal cutoff (Youden) for a continuous biomarker; and post-test probability via Bayes. Use when you have test results vs a gold standard (binary 2x2, or a continuous score + true labels) and need to judge how good the test is, pick a threshold, or compute the probability of disease given a result. Emphasizes the prevalence-dependence of PPV/NPV.

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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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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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Creative research ideation and exploration. Use for open-ended brainstorming sessions, exploring interdisciplinary connections, challenging assumptions, or identifying research gaps. Best for early-stage research planning when you do not have specific observations yet. For formulating testable hypotheses from data use hypothesis-generation.

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Produce and interpret PCA, t-SNE, UMAP, and PHATE plots for high-dimensional omics data with rigor about which method preserves what (variance, local structure, manifold, transitions), hyperparameter sensitivity, and the well-documented limits of 2D embeddings. Covers PCA biplot/scree/loadings, t-SNE PCA initialization (Kobak-Berens 2019), UMAP n_neighbors/min_dist trade-offs, and the Chari-Pachter 2023 critique. Use when visualizing high-dimensional data — bulk PCA, single-cell embeddings, multi-omics integration projections.

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Build publication-quality figures in R with ggplot2 using the grammar of graphics (data + aesthetics + geometries + scales + facets + themes) with CVD-safe palettes, cairo_pdf TrueType embedding, programmatic aes via tidy evaluation, and the theme_classic publication baseline. Use when producing static figures in R for papers, presentations, or reports.

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Quantum physics simulation library for open quantum systems. Use when studying master equations, Lindblad dynamics, decoherence, quantum optics, or cavity QED. Best for physics research, open system dynamics, and educational simulations. NOT for circuit-based quantum computing—use qiskit, cirq, or pennylane for quantum algorithms and hardware execution.

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Reads, validates, and prepares CDISC SDTM and ADaM clinical trial data for analysis. Covers SDTM domain joins (DM, AE, EX, VS, LB, DS), ADaM architecture (ADSL, BDS, OCCDS, ADTTE) with traceability, treatment-emergent AE conventions, baseline derivation, SUPPQUAL/NSV handling, Define-XML 2.1, and Pinnacle 21 / CORE validation. Use when working with clinical trial datasets in CDISC SDTM/ADaM format, preparing analysis-ready data, or validating for regulatory submission.

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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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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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Statistical modeling — linear/logistic/ordinal/Poisson regression, ANOVA, Kruskal-Wallis, chi-square, Mann-Whitney, Cox survival, spline fits (R `ns()`), odds ratios, Cohen's d, F-statistic, p-value computation. Specializes in clinical-trial AE analysis (SDTM DM/AE), severity ordinal regression, and per-feature stat workflows.

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Build circular genome visualizations using circlize (R), pyCirclize (Python), or Circos (Perl CLI) with ideogram tracks, multi-data tracks (scatter, histogram, heatmap), chord/link arcs for interactions, and explicit circos.clear() between plots. Covers when circular is appropriate vs when Cartesian wins (Cleveland-McGill 1984), karyograms, and chromosome adjacency in chord diagrams. Use when adjacency on the circle conveys meaning — chromosome-level overview, structural variants, Hi-C interactions, cross-genome comparisons.

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Plot per-group distributions of continuous data using boxplots, violins, beeswarms, quasirandom jitter, and raincloud plots with sample-size honesty (Weissgerber 2015), KDE-bandwidth awareness, and N-aware encoding choices. Use when comparing distributions across a small number of groups — expression per cluster, biomarker per arm, scores per condition — and the bar-of-mean default is misleading.

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Build Sankey, alluvial, river, and CONSORT-style flow diagrams to visualize cohort transitions, cell-state changes, or pipeline filtering using ggalluvial, networkD3, plotly, and consort. Use when showing how entities move between categories across timepoints (cell states, drug response classes, patient flow through a trial) or filtering pipelines (variants filtered through QC stages).

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Hardware-agnostic quantum ML framework with automatic differentiation. Use when training quantum circuits via gradients, building hybrid quantum-classical models, or needing device portability across IBM/Google/Rigetti/IonQ. Best for variational algorithms (VQE, QAOA), quantum neural networks, and integration with PyTorch/JAX/TensorFlow. For hardware-specific optimizations use qiskit (IBM) or cirq (Google); for open quantum systems use qutip.

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IBM quantum computing framework. Use when targeting IBM Quantum hardware, working with Qiskit Runtime for production workloads, or needing IBM optimization tools. Best for IBM hardware execution, quantum error mitigation, and enterprise quantum computing. For Google hardware use cirq; for gradient-based quantum ML use pennylane; for open quantum system simulations use qutip.

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Designs adaptive clinical trials including group-sequential (O'Brien-Fleming, Pocock, Lan-DeMets spending), sample-size re-estimation (blinded Friede-Kieser, unblinded Cui-Hung-Wang, Mehta-Pocock promising zone), seamless Phase 2/3 with treatment-arm selection, population enrichment, and response-adaptive randomisation. Covers FDA 2019 Final Adaptive Designs Guidance, FDA 2022 Master Protocols, and ICH E20 Step 2b/3 draft (June 2025, NOT final). Use when planning interim analyses, sample-size re-estimation, or master/platform-trial designs.

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Tests associations between categorical variables in clinical data using chi-square, Fisher's exact, Boschloo, Cochran-Mantel-Haenszel, and modern McNemar variants with calibrated confidence intervals (Wilson, Newcombe, Miettinen-Nurminen). Use when analyzing categorical outcomes, paired binary endpoints, or testing treatment-outcome independence in confirmatory or exploratory clinical trials.

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Google quantum computing framework. Use when targeting Google Quantum AI hardware, designing noise-aware circuits, or running quantum characterization experiments. Best for Google hardware, noise modeling, and low-level circuit design. For IBM hardware use qiskit; for quantum ML with autodiff use pennylane; for physics simulations use qutip.

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Controls error rates across thousands of simultaneous tests in genomics discovery using false-discovery-rate methods (Benjamini-Hochberg 1995; Benjamini-Yekutieli 2001 for arbitrary dependence; Storey q-value with pi0 estimation; local FDR; independent filtering Bourgon 2010; covariate-weighted FDR via IHW Ignatiadis 2016), plus family-wise error control (Bonferroni, Holm) and the GWAS genome-wide threshold. Covers the FDR-versus-FWER choice as the discovery-versus-confirmatory distinction, the dependence assumptions behind BH (PRDS) versus BY, pi0 estimation, the independent-filtering and false-coverage-rate traps, and reproducibility ranking via IDR (Li 2011). Use when correcting p-values from genome-wide tests, choosing between BH/BY/q-value/Bonferroni, setting an FDR threshold, applying IHW or independent filtering, or interpreting q-values. For confirmatory trials with few pre-specified endpoints (closed testing, graphical/gatekeeping), see clinical-biostatistics/multiplicity-graphical.

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Simulate wave propagation — acoustic, electromagnetic, elastic, and quantum waves. FDTD, spectral methods, and absorbing boundary conditions for 1D/2D/3D wave equations with sources, scattering, and dispersion.

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Discover governing equations from data using PySR (evolutionary symbolic regression). Physics-constrained search with dimensional analysis, custom operators, and complexity-accuracy tradeoffs. Use when you need an interpretable equation, not a black-box model.

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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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Plot per-gene mutation distributions on a protein-domain map (lollipop / needle plots) showing mutation position, recurrence count, and variant classification with maftools, g3-lollipop, trackViewer, and ProteinPaint. Use when visualizing recurrent mutation hotspots on a single gene's protein, marking domain boundaries from UniProt/Pfam, comparing missense vs truncating distributions, or contrasting two cohorts on the same lollipop.

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