「sample」の検索結果

Designs complete single-cell research plans from a user-provided biomedical direction. Always use this skill whenever a user wants to design, scope, or structure a single-cell study — including disease-focused, mechanism-focused, biomarker-focused, translational, perturbation-inspired, or validation-aware projects. It should define the research question, choose the best-fit study pattern, recommend sample grouping logic, suggest reference datasets as examples only, specify the core analysis modules, propose a validation ladder, and output four workload configurations (Lite / Standard / Advanced / Publication+). Never fabricate datasets, sample metadata, accession numbers, cohort availability, cell-type labels, external validation resources, or literature references. Always include the mandatory Dataset Disclaimer immediately before any workflow section that mentions datasets or public resources.

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Generates complete two-sample Mendelian randomization research designs from a user-provided outcome, exposure or exposure family, and robustness direction. Use when a study centers on summary-statistics causal inference with instrument selection, harmonization, IVW-primary estimation, complementary estimators, sensitivity analyses, optional multivariable upgrades, and conservative evidence interpretation. Covers five study patterns and always outputs Lite / Standard / Advanced / Publication+ with a recommended primary plan, stepwise workflow, figure plan, validation hierarchy, minimal executable version, publication upgrade path, and strictly verified literature retrieval.

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Plans sample size estimation logic, power assumptions, feasibility checks, and fallback enrollment strategies for clinical and translational study protocols.

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Use when performing sample-level dimensionality reduction and visualization on abundance or OTU-style matrices with a companion group file, generating UMAP and/or t-SNE coordinates and plots for group separation assessment. NOT for: differential expression testing, single-cell workflows requiring dedicated embeddings pipelines, or analyses without a sample grouping file.

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Use when filtering genes with high missingness and then imputing missing values in a bulk expression matrix with group-aware KNN through DMwR2, where donor samples are restricted by one annotation column before imputation. For strata with 10 or fewer samples, the script falls back to row-wise direct filling with mean or median. NOT for: single-cell data, multi-column stratification, non-tabular inputs, network access, or interactive workflows.

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Acknowledges limitations in sample, design, measurement, and validation in a professional way that improves credibility without undermining the whole paper. Use when writing the limitations paragraph of a Discussion section, preparing a grant risk assessment, responding to reviewers about study weaknesses, or framing scope boundaries for a paper. Also triggers on "write my limitations", "how should I address the limitation of", "reviewer said my sample is too small", or "help me word this limitation".

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Use this skill when writing analytical SQL over time-series data with the TimescaleDB Toolkit (timescaledb_toolkit extension) hyperfunctions: approximate percentiles, statistical summaries, time-weighted averages, counter/gauge rates, uptime/heartbeat tracking, state durations, OHLC candlesticks, approximate distinct counts, top-N, and downsampling. **Trigger when user asks to:** - Compute percentiles/medians/p95/p99 over large or rolled-up time-series data - Compute rates or deltas from monotonic counters (Prometheus-style) or gauges - Compute time-weighted averages or integrals over irregularly sampled data - Track uptime/downtime from heartbeats, or time spent in each state - Build OHLC/candlestick or VWAP data for financial ticks - Store re-aggregatable summaries in continuous aggregates (two-step aggregation, rollup) - Approximate COUNT DISTINCT, find top-N / most frequent values, or downsample for charts **Keywords:** timescaledb_toolkit, hyperfunctions, percentile_agg, uddsketch, tdigest, approx_percentile, stats_agg, time_weight, counter_agg, gauge_agg, heartbeat_agg, state_agg, candlestick_agg, hyperloglog, approx_count_distinct, min_n, max_n, mcv_agg, lttb, asap_smooth, rollup, two-step aggregation

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Compute statistical power, required sample size, and minimum detectable effect (MDE) for a study design, then write a registry-ready power section. Handles two-arm RCTs (with clustering / ICC and unequal allocation), multiple-arm corrections, and a simulation-based power option for non-standard designs (DiD/event-study, IV, panel). Use when user says "power analysis", "power calculation", "MDE", "minimum detectable effect", "how big a sample do I need", "is my study powered", "power for an RCT", or when /preregister needs a power section for an experiment. Produces a power/MDE table, power curves, and a methods paragraph to paste into a preregistration.

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Design statistically rigorous A/B tests for product features, UI changes, onboarding flows, and pricing experiments. Use when asked to set up an experiment, design an A/B test, calculate sample size, or interpret test results. Produces a complete test plan with hypothesis, variant definitions, sample size, duration estimate, guardrail metrics, and a results interpretation guide.

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Balances Hi-C contact matrices (ICE via cooler.balance_cooler, KR/SCALE/VC context), computes distance-decay expected with cooltools (expected_cis per-diagonal P(s), expected_trans scalar), builds observed/expected (O/E) matrices, and diagnoses polymer state from the P(s) log-derivative. Covers the within-matrix-vs-cross-sample distinction (balancing is NOT a normalizer), the equal-visibility assumption that CNV/aneuploidy violates (use raw counts for copy-number), cis-only balancing, mad_max/blacklist masking before balancing, multiplicative cooler weights vs divisive juicer weights, and the resolution-vs-depth budget. Use when balancing a .cool/.mcool, computing expected or P(s), making O/E matrices for compartments/loops, deciding ICE vs KR vs SCALE, choosing a resolution for a given depth, or troubleshooting NaN/all-NaN balanced matrices; route cross-sample comparison to hic-differential.

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Compares Hi-C contact maps between conditions across the right scale -- differential bin-pair contacts (multiHiCcompare, diffHic), differential A/B compartments (dcHiC), differential TAD boundaries (delta insulation), and differential loops (diffloop, DiffHiChIP) -- with distance-stratified between-sample normalization, replicate-aware NB-GLM FDR, HiCRep SCC reproducibility gating, and CNV correction for cancer/aneuploid samples. Use when comparing Hi-C between treatment and control, finding differential contacts/compartments/boundaries/loops, normalizing two maps of unequal depth, choosing a replicate-aware test, gating replicates with SCC, or correcting copy-number artifacts before a tumor-vs-normal comparison.

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Generates, normalizes, and converts bedGraph signal tracks (4-column chrom/start/end/value, 0-based half-open) with bedtools genomecov, deepTools bamCoverage/bamCompare/bigwigCompare, bedtools unionbedg, and UCSC bedGraphToBigWig. Covers why a raw coverage bedGraph is not comparable across samples until normalized, the CPM/RPKM/BPM/RPGC normalization menu and the conserved-total assumption that makes them wrong under a global perturbation, the strict sorted-non-overlapping-chrom.sizes bedGraphToBigWig contract that silently corrupts a bigWig, effective-genome-size selection, and bin-size aliasing. Use when building or normalizing a coverage/signal track from a BAM, comparing tracks across samples or conditions, converting bedGraph to a browser-ready bigWig, or diagnosing a track that looks plausible but reports wrong heights.

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Normalizes and transforms RNA-seq count matrices for DE, visualization, clustering, and ML. Covers between-sample (TMM, TMMwsp, RLE/median-of-ratios, upper quartile), within-sample (TPM, FPKM/RPKM), variance-stabilizing (VST, rlog, log-CPM), GC-content correction (cqn, EDASeq), and single-cell (scran deconvolution, scanpy normalize_total). Encodes the composition-bias rationale, the "most genes not DE" assumption and its catastrophic failure modes (MYC amplification, apoptosis, viral host shutoff, prokaryotic stress), the "lengthScaledTPM is not TPM" naming trap, the "TPM is not for DE" rule, the blind=TRUE vs FALSE decision, ERCC spike-in normalization (SBN), and the single-cell zero-inflation breakdown of TMM/RLE. Use when choosing or applying normalization, debugging shifted-MA-plot diagnostics, handling zero-heavy single-cell data, or correcting GC bias.

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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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Build OncoPrint and co-mutation matrix plots from somatic-variant cohorts using ComplexHeatmap, maftools, and comut.py with alteration-type stacking, sample ordering by mutational burden, mutual-exclusivity overlays, and clinical annotation tracks. Use when visualizing per-sample mutation patterns across recurrent driver genes, comparing alteration classes, or identifying mutually-exclusive / co-occurring driver pairs.

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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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Performs differential expression on bulk RNA-seq count data with edgeR's negative-binomial GLM and quasi-likelihood F-test framework. Covers DGEList construction, filterByExpr, TMM/TMMwsp normalization, robust dispersion estimation, glmQLFit/glmQLFTest, TREAT for magnitude-bounded hypotheses, contrasts via no-intercept designs, voom and voomWithQualityWeights for heterogeneous samples, and the edgeR v4 bias-corrected APL changes. Use when running bulk DE with edgeR, choosing edgeR over DESeq2 (small n, transcript DE via catchSalmon, large samples), needing TREAT for a fold-change-threshold hypothesis, troubleshooting v3-to-v4 reproducibility, building paired or interaction designs, or handling library-quality heterogeneity.

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Quantifies CRISPR editing outcomes with CRISPResso2 (Clement 2019 Nat Biotechnol) across Cas9-nuclease (indels, HDR), CBE and ABE base editors (target conversion + bystander), and prime editor (pegRNA-templated) modes. Covers single-amplicon (CRISPResso), multi-sample batch (CRISPRessoBatch), pooled-amplicon (CRISPRessoPooled), WGS off-target (CRISPRessoWGS), and sample-comparison (CRISPRessoCompare) workflows; quantification-window math that controls what is called edited; substitution-vs-indel diagnostic to distinguish BE from Cas9 contamination; MMEJ deletion pattern interpretation; allele-frequency tables; and failure modes from amplicon misalignment or contamination. Use when quantifying editing from amplicon sequencing, choosing CRISPResso mode by design, distinguishing intended edits from bystanders and indel byproducts, debugging low-alignment runs, or generating publication-grade editing reports.

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Segments the genome into chromatin states from combinatorial histone modification and chromatin factor ChIP-seq data. Uses ChromHMM (multivariate HMM on binarized signal, v1.27), Segway (Dynamic Bayesian Network on continuous signal), EpiSegMix (flexible-distribution HMM with duration modeling, 2024), EpiLogos (multi-biosample visualization), IDEAS (cell-type-aware joint), and full-stack ChromHMM (Vu Ernst 2022) for cross-cell-type segmentations. Handles state-count selection (15 vs 18 vs 25 states), binarization choice, OverlapEnrichment / NeighborhoodEnrichment downstream analysis, and cross-biosample integration. Use when learning chromatin states from a histone mark panel, characterizing learned states by genomic feature enrichment, or comparing chromatin landscapes across cell types.

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Computes sample size and power for clinical trials including continuous, binary, and time-to-event endpoints; superiority, non-inferiority, and equivalence designs; FDA 2016 non-inferiority margin selection with M1/M2 framework; Schoenfeld 1981 and Lakatos 1988 for survival; Schuirmann TOST and 80-125% bioequivalence; minimum clinically important difference (MCID) vs δ distinction. Use when justifying trial size in protocol or SAP per CONSORT 2025 item 16a.

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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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Queries gnomAD v4 (807k samples), v3, v2.1.1, and constraint metrics with grpmax FAF95, bottleneck-group exclusion, LOEUF interpretation, SV/CNV/mtDNA catalogs, and Whiffin max-credible-AF framework. Use when filtering rare variants, applying ACMG BS1/BA1, ranking genes by LoF intolerance, or selecting between v2 (GRCh37 + chrX/Y constraint) and v4 (GRCh38 + 807k samples).

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Analyze TF motif accessibility variability across samples or single cells using chromVAR. Use when identifying TF motifs whose accessibility correlates with conditions, computing per-sample motif z-scores after matched background correction, comparing to ArchR / Signac equivalents, or distinguishing motif-accessibility signal from per-site footprinting.

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Estimates bivariate genetic correlation (rg) between traits from GWAS summary statistics or individual-level genotypes using cross-trait LDSC, HDL, LAVA, rho-HESS, GREML-bivariate, Popcorn, and HDL-L. Use when quantifying shared genetic architecture between two traits, screening MR validity before causal inference, distinguishing global from locus-level rg, estimating trans-ancestry rg, separating partial from full causation via LCV gcp, or producing a STROBE-MR-compliant cross-trait sensitivity battery. Cross-trait LDSC intercept absorbs sample overlap and is NOT a bias; HDL is biased under sample overlap above ~5%. High rg between exposure and outcome motivates CHP-aware MR sensitivity (CAUSE, LHC-MR).

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