Test design, vulnerability assessment, and quality assurance (13K skills)
Perform differential expression analysis using edgeR in R/Bioconductor. Use for analyzing RNA-seq count data with the quasi-likelihood F-test framework, creating DGEList objects, normalization, dispersion estimation, and statistical testing. Use when performing DE analysis with edgeR.
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Identify differentially bound regions across CLIP-seq conditions (knockdown vs control, treatment vs vehicle, disease vs healthy) using DEWSeq (sliding-window DESeq2), Flipper (Skipper-downstream), ASpeak, edgeR, or limma-voom. Use when computing condition-level changes in RBP binding intensity, choosing peak-level vs window-level vs crosslink-level testing, designing replicate experiments, or distinguishing biological binding shifts from technical confounders.
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Per-CpG differential methylation testing from bisulfite sequencing count data or beta-value matrices. Covers beta and M-value computation, coverage filtering, statistical tests (Welch t-test, Mann-Whitney, limma, DSS beta-binomial), multiple testing correction, and effect size calculation. Use when comparing methylation at individual CpG sites between experimental groups from WGBS, RRBS, or targeted bisulfite sequencing.
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Differential abundance testing for microbiome data using compositionally-aware methods like ALDEx2, ANCOM-BC2, and MaAsLin2. Use when identifying taxa that differ between experimental groups while accounting for the compositional nature of microbiome data.
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Alpha and beta diversity analysis for microbiome data. Calculate within-sample richness, evenness, and between-sample dissimilarity with phyloseq and vegan. Use when comparing community composition across samples or testing for group differences in microbiome structure.
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Differential abundance and state analysis for cytometry data. Compare cell populations between conditions using statistical methods. Use when testing for significant changes in cell frequencies or marker expression between groups.
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Extract, filter, annotate, and export differential expression results from DESeq2 or edgeR. Use for identifying significant genes, applying multiple testing corrections, adding gene annotations, and preparing results for downstream analysis. Use when filtering and exporting DE analysis results.
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Detects circadian and ultradian rhythms in time-series omics data using CosinorPy cosinor models, MetaCycle (JTK_CYCLE, ARSER), and RAIN non-parametric tests. Fits cosine models to estimate phase and amplitude, tests rhythmicity significance at pre-specified periods. Use when testing for 24-hour or other known-period oscillations in circadian, feeding-fasting, or light-dark cycle experiments. Not for unknown-period discovery (see temporal-genomics/periodicity-detection).
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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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Analyzes community composition using constrained ordination (CCA, RDA, db-RDA), variance partitioning (varpart), indicator species analysis (indicspecies multipatt), and distance-based environmental gradient methods with vegan. Links species composition to environmental explanatory variables. Use when testing how environmental gradients structure species communities, identifying habitat indicator taxa, or partitioning explained variation among predictors. Not for basic unconstrained ordination and PERMANOVA (see microbiome/diversity-analysis).
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Assesses ChIP-seq quality across antibody specificity, fragmentation, enrichment, replicate concordance, and library complexity. Computes FRiP, NSC/RSC (phantompeakqualtools), library complexity (NRF/PBC1/PBC2), deepTools plotFingerprint (JS distance, AUC, synthetic JS), ChIPQC, IDR with ENCODE Nself/Nt rules, and detects hyper-ChIPable artifacts. Use when validating an antibody, diagnosing failed peak calls, deciding whether to proceed with downstream analysis, grading against ENCODE thresholds, or auditing replicate concordance.
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Test whether two or more traits share a causal variant at a locus using Bayesian colocalization (coloc.abf, coloc.susie, HyPrColoc, moloc, eCAVIAR, SMR/HEIDI, PWCoCo, SharePro). Use when integrating GWAS with eQTL/sQTL/pQTL/mQTL, distinguishing shared causal variants from LD-driven coincidence, handling allelic heterogeneity, choosing between single-causal vs multi-causal methods, picking PP.H4 thresholds, running sensitivity over p12, or harmonising summary statistics for colocalization.
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Reconstruct ancestral states at internal phylogenetic nodes for sequences (PAML codeml, IQ-TREE --ancestral, GRASP, FastML), discrete traits (corHMM hidden-rate Markov, ape::ace, phytools::make.simmap stochastic mapping, BayesTraits), and continuous traits (phytools::fastAnc, geiger Brownian/OU, RPANDA). Use when designing constructs for ancestral protein resurrection, tracing trait evolution along a tree, performing stochastic character mapping, testing models of trait evolution (BM vs OU vs EB), inferring ancestral genome content via Dollo or DTL reconciliation, or quantifying ancestral-state uncertainty for downstream comparative analyses.
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Detects allele-specific transcription factor or histone modification binding from heterozygous-variant ChIP-seq using WASP (reference-bias filter; mandatory upstream), RASQUAL (joint QTL + bias-corrected testing), BaalChIP (Bayesian beta-binomial with copy-number-aware overdispersion), and AlleleSeq (personalized diploid genome). Handles imprinted-locus awareness, X-inactivation artifacts, cancer copy-number imbalance, and integration with downstream caQTL / bQTL mapping. Use when identifying variants with allelic effects on TF binding, fine-mapping causal regulatory variants, validating deep-learning variant predictions, or characterizing cis-acting regulatory effects.
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Statistical testing for differentially abundant proteins between conditions. Covers preprocessing (log2 transformation, normalization), limma and DEqMS workflows with empirical Bayes moderation, fold change shrinkage for accurate effect size estimation, and Python alternatives. Use when identifying proteins with significant abundance changes between experimental groups.
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Genome-wide association studies (GWAS) with PLINK. Perform case-control and quantitative trait association testing using logistic/linear regression with covariates, generate Manhattan and QQ plots for result visualization. Use when running GWAS or association tests.
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Workflow for enrichment testing, ranked-gene analysis, pathway scoring, and pathway-focused visualization across omics outputs.
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Binder design ranking using ipSAE (interprotein Score from Aligned Errors). Use this skill when: (1) Ranking binder designs for experimental testing, (2) Filtering BindCraft or RFdiffusion outputs, (3) Comparing AF2/AF3/Boltz predictions, (4) Predicting binding success rates, (5) Need better ranking than ipTM or iPAE. For structure prediction, use chai or alphafold. For QC thresholds, use protein-qc.
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Grounded in first principles, rigorously examine and refine a user's plan, task, decision, goal, strategy, proposal, or idea through structured, progressively deeper questioning, in order to bridge the gap between the User and the Agent. Use when the user explicitly requests grilling, challenge, pressure-testing, cross-examination, red-team review, pre-mortem analysis, or a decision audit. The goal is to uncover unclear objectives, hidden assumptions, contradictions, weak evidence, missing information, overlooked constraints, dependencies, risks, trade-offs, failure modes, and misalignment between intended outcomes and likely real-world results. Begin by establishing a shared understanding of the user's actual intent, goals, constraints, and success criteria. Ask focused, high-leverage questions rather than broad or repetitive ones. Adapt each question based on previous answers, probing deeper where uncertainty, unsupported assumptions, or strategic weaknesses remain. Regularly summarize the current understanding of the user's intent and position to confirm alignment, expose misunderstandings, and refine the problem or goal definition. Distinguish facts, assumptions, hypotheses, and unknowns. Challenge reasoning rigorously while remaining constructive, respectful, and solution-oriented. Continue until the reasoning is internally coherent, evidence-aware, constraint-conscious, risk-assessed, and translated into a clearer, more actionable goal, decision, or plan. Ultimately, achieving the super-alignment.
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Audit a website's content, structure, SEO health, and technical setup through SandBase. Use when asked for website audit, content audit, SEO health check, site structure analysis, or technical assessment.
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Plan, implement, or review test driven development work in an existing codebase with compatibility, security, and verification controls. Use when the user explicitly requests test driven development work.
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Plan, implement, or review google cloud waf security work in an existing codebase with compatibility, security, and verification controls. Use when the user explicitly requests google cloud waf security work.
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Plan, implement, or review kubernetes security policies work in an existing codebase with compatibility, security, and verification controls. Use when the user explicitly requests kubernetes security policies work.
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Create or review audit support deliverables with traceable assumptions, decision criteria, ownership, and risk controls. Use when the user asks for audit support planning or analysis.
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