测试与安全技能

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.

中文简介正在准备中。当前显示原文说明。

Performs differential expression on bulk RNA-seq count data with DESeq2's negative-binomial GLM, Wald and LRT testing, apeglm/ashr/normal LFC shrinkage, independent filtering, Cook's outlier handling, VST/rlog transforms, and design formulas including paired, batch, and interaction terms. Use when running bulk DE, choosing DESeq2 over edgeR or limma-voom, building a paired or interaction design, applying LFC shrinkage for ranking or GSEA, choosing Wald vs LRT, troubleshooting padj=NA, picking VST vs rlog, importing salmon/kallisto via tximport, or analyzing prokaryotic RNA-seq.

中文简介正在准备中。当前显示原文说明。

Analyzes pooled CRISPR screens with MAGeCK (Li et al 2014), covering count generation (mageck count), the RRA two-condition workflow (mageck test using alpha-RRA over per-sgRNA negative-binomial p-values), the MLE multi-condition workflow (mageck mle with explicit design matrix and beta-score output), normalization choice (median vs total vs control-sgRNA vs spike-in), sgRNA efficiency injection, paired-sample testing, time-course design, drug-screen versus dropout-screen design matrices, MAGeCKFlute and MAGeCK-VISPR downstream visualization, and decision logic for when to use MAGeCK vs JACKS / BAGEL2 / drugZ / Chronos. Use when running a fresh CRISPR screen analysis, picking RRA vs MLE for the experimental design, choosing a normalization method from QC signatures, debugging MLE convergence failure or NaN beta scores, comparing MAGeCK output across tools, or building a batch-aware multi-cell-line / multi-condition MLE design matrix.

中文简介正在准备中。当前显示原文说明。

Analyzes species-environment relationships with constrained ordination (CCA, RDA, db-RDA), variance partitioning, indicator species (indicspecies IndVal.g group-equalized), PERMANOVA paired MANDATORILY with PERMDISP (Anderson & Walsh 2013; dispersion confounds centroid tests), Joint Species Distribution Models (HMSC, sjSDM, gjam) with explicit rejection of "residual covariance equals biotic interaction", phylogenetic community ecology (SES_MPD/MNTD), trait-environment via RLQ + fourth-corner with corrected modeltype=6 (Dray 2014), bipartite network metrics (NODF, modularity) with curveball null (Strona 2014), and Mantel-test replacements (dbRDA, GDM) for spatial data. Use when testing how environmental gradients structure communities, identifying habitat indicator taxa, partitioning variance among predictors, deciding whether PERMANOVA significance is location vs dispersion, picking among HMSC/sjSDM/gjam, or replacing Mantel tests for landscape data.

中文简介正在准备中。当前显示原文说明。

Extracts, filters, annotates, and exports differential expression results from DESeq2 or edgeR with proper handling of padj=NA (independent filtering, Cook's outliers, all-zero), multiple-testing correction choice (BH vs Storey q-value vs IHW vs lfsr), TREAT vs post-hoc fold-change filtering, p-value histogram diagnostics, gene annotation via org.db/biomaRt/mygene, GSEA preranked input, ORA background construction, replication reality (Schurch 2016 small-n result), and SABV/sex-stratified reporting. Use when extracting and interpreting DE results, troubleshooting padj=NA, choosing FDR method, preparing ranked lists for pathway analysis, annotating gene IDs, or comparing DESeq2 vs edgeR outputs.

中文简介正在准备中。当前显示原文说明。

Handles batch effects in bulk RNA-seq via design-matrix inclusion (the correct path for DE), ComBat/ComBat-seq for visualization, SVA for unknown latent factors, RUVSeq for negative-control-gene-anchored unwanted variation, and limma::removeBatchEffect for plotting only. Encodes the Nygaard 2016 cardinal sin against testing on a batch-corrected matrix, the choice between SVA/RUVg/RUVs/RUVr, the confounding non-identifiability problem, the single-cell boundary (Harmony/MNN are NOT for bulk), and the Goh 2017 harmonization critique. Use when designing a DE analysis with batch structure, troubleshooting batch-dominated PCA, choosing ComBat vs ComBat-seq, handling unknown batch via SVA, integrating across studies, or deciding when (rarely) to subtract batch.

中文简介正在准备中。当前显示原文说明。

Detect, date, and contextualize whole-genome duplication (WGD / paleopolyploidy) events using wgd v2 (Chen et al 2024), KsRates (Sensalari 2022 substitution-rate-corrected Ks dating), DupGen_finder (Qiao 2019), MAPS (Li 2018 phylogenomic), POInT (Conant 2008 ordered-block), SLEDGe (2024 ML-based), Whale.jl (Bayesian DL+WGD), and synteny-anchored paranome construction. Use when identifying ancient polyploidy from Ks distributions and synteny block analysis, positioning WGD events relative to speciation, distinguishing tandem from segmental from WGD duplications, dating the 2R/3R vertebrate / fish / salmonid WGDs, building paranome and Ks-age mixture models, applying KsRates substitution-rate correction across lineages, or testing alternative biased-fractionation / dosage-balance models post-WGD.

中文简介正在准备中。当前显示原文说明。

Cross-method decision tree for calling hits in pooled CRISPR screens. Catalogs statistical models (MAGeCK RRA, MAGeCK MLE, BAGEL2, drugZ, JACKS, Chronos, CERES), experimental designs each is built for, failure modes outside design domain, reconciliation when methods disagree, multiple-testing and effect-size thresholds, the order of operations (count -> QC -> CN-correct -> hit-call -> validate), the second-best-sgRNA conservative rule, and consensus-hit strategy. Use when choosing among MAGeCK / BAGEL2 / drugZ / JACKS / Chronos for a given design, reconciling disagreement across two or three methods on the same screen, deciding whether to require consensus, gating downstream validation by hit-confidence tier, or interpreting unstable hit lists across reruns.

中文简介正在准备中。当前显示原文说明。

Model gene-family birth-death dynamics across a species tree using CAFE5 (Mendes et al 2020 Bioinformatics 36:5516 gamma-distributed rate categories), CAFE5-error (annotation-error-aware), Count (Csurös 2010 ancestral state reconstruction), BadiRate (Librado 2012 likelihood + parsimony), DupliPHY-Family, and ALE/AleRax (for per-family DTL; see [[gene-tree-species-tree-reconciliation]]). Test lineage-specific gene-family expansions and contractions, distinguish biological dynamics from annotation artifacts, account for assembly fragmentation, identify functional enrichment in expanded / contracted families. Use when correlating gene-family changes with phenotype evolution, ranking lineages by adaptive gene-family-rate shifts, post-WGD dosage-balance analysis, or building Birth-death models from OrthoFinder presence/absence matrices.

中文简介正在准备中。当前显示原文说明。

Detect introgression and admixture between species or populations using Dsuite (Malinsky 2021 fast D-statistics), Patterson's D / ABBA-BABA test (Green 2010; Durand 2011), f4-ratio and f-branch statistic (Malinsky 2018), TreeMix (Pickrell & Pritchard 2012), HyDe (Blischak 2018), QuIBL (Edelman 2019), sprime (Browning 2018), Twisst (Martin 2017), PhyloNet (Than 2008) for explicit phylogenetic networks, and qpAdm / qpGraph (Patterson 2012). Distinguish introgression from incomplete lineage sorting (ILS), ancestral structure, ghost-lineage admixture, and rate variation. Use when testing inter-species gene flow, dating admixture events, identifying introgressed segments, building phylogenetic networks for reticulate evolution, or applying the ABBAclustering (Koppetsch-Malinsky-Matschiner 2024) framework for divergent-species gene flow.

中文简介正在准备中。当前显示原文说明。

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.

中文简介正在准备中。当前显示原文说明。

Detect positive (diversifying / episodic / pervasive) selection using codon dN/dS frameworks. Implements PAML codeml site models (M0/M1a/M2a/M7/M8/M8a), branch models, branch-site model A (Zhang 2005), and HyPhy methods (BUSTED, BUSTED-S, BUSTED-MH, BUSTED-PH, MEME, FEL, FUBAR, aBSREL, SLAC, RELAX, GARD, FUBAR-MH). Includes McDonald-Kreitman framework (asymptotic alpha, impMKT, polyDFE, DFE-alpha, GRAPES) for within-species + divergence inference, RERconverge for trait-correlated rate shifts, CSUBST for convergent substitution, and PhyloAcc for accelerated noncoding evolution. Use when testing adaptive evolution at codons, branches, or full gene; running GARD recombination pre-screen; controlling alignment-error and gBGC false positives; reconciling PAML vs HyPhy results; or performing genome-scale selection scans.

中文简介正在准备中。当前显示原文说明。

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.

中文简介正在准备中。当前显示原文说明。

Build and analyze pangenomes for prokaryotes (Panaroo, PPanGGOLiN, PEPPAN, GET_HOMOLOGUES, anvi'o pangenomics) and eukaryotes (Minigraph-Cactus, PGGB, vg pangenome graphs). Implement Tettelin core/accessory/cloud genome decomposition (Tettelin 2005), Heap's law open/closed pangenome modeling, gene presence/absence GWAS (Scoary, pyseer), pangenome graph variant calling (vg, PanGenie), and structural-variation graph indexing. Use when assembling species- or genus-level pan-gene catalogs, separating core from accessory/shell/cloud genes, testing gene-content associations with phenotypes, building pangenome graphs from haplotype-resolved assemblies, calling SVs from pangenome graphs, or selecting between bacterial-pangenome and eukaryotic-pangenome workflows.

中文简介正在准备中。当前显示原文说明。

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.

中文简介正在准备中。当前显示原文说明。

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.

中文简介正在准备中。当前显示原文说明。

Validates docked / generated protein-ligand poses using PoseBusters physical-validity tests, strain energy quantification, geometric checks (planarity, vdW overlap, bond/angle distortion), and pose-energy reasonableness. Use when QC-ing docking results, comparing classical vs ML docking outputs, or filtering pose lists before SAR analysis.

中文简介正在准备中。当前显示原文说明。

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.

中文简介正在准备中。当前显示原文说明。

Discovers de novo motifs and tests known motif enrichment in ChIP-seq, ATAC-seq, or other peak sequences using HOMER, MEME-ChIP (STREME, CentriMo, TOMTOM, FIMO), monaLisa, and AME. Handles background selection (GC-matched, dinucleotide-shuffled, Markov order-2, peak-flanks), motif databases (JASPAR 2024 CORE PWMs, JASPAR 2026 deep-learning collection, HOCOMOCO v12, HOMER built-in), centrally-enriched motif testing, and differential motif analysis. Use when identifying TF binding motifs in peaks, testing for known TF enrichment, scanning for motif instances, comparing motif content between conditions, or interpreting motifs from deep learning models.

中文简介正在准备中。当前显示原文说明。

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.

中文简介正在准备中。当前显示原文说明。

Decompose total effects into direct and indirect paths through mediators using mediation, CMAverse 4-way, HIMA/HIMA2 high-dimensional, BAMA, two-step / MVMR mediation, or double-ML medDML. Use when testing whether a molecular phenotype (expression, methylation, protein) mediates a treatment-outcome relationship, decomposing exposure-mediator interaction via VanderWeele 4-way, screening high-dimensional EWAS mediators, or running MR-based mediation when sequential ignorability is implausible.

中文简介正在准备中。当前显示原文说明。

Estimate causal effects of an exposure on an outcome from GWAS summary statistics using genetic instruments. Implements IVW (fixed/random), MR-Egger, weighted median/mode, MR-RAPS, CAUSE, GSMR-HEIDI, MR-PRESSO, MVMR, MR-Clust, LCV, and LHC-MR via TwoSampleMR, MendelianRandomization, MR-PRESSO, cause, and lhcMR. Use when testing causal direction between traits, evaluating drug-target effects via cis-pQTL/cis-eQTL, performing multivariable mediation MR, distinguishing causation from correlated horizontal pleiotropy, or producing STROBE-MR-compliant sensitivity batteries.

中文简介正在准备中。当前显示原文说明。

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.

中文简介正在准备中。当前显示原文说明。

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.

中文简介正在准备中。当前显示原文说明。