「dr」の検索結果

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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Assembles a genome de novo from Illumina short reads with SPAdes (isolate/careful/sc/meta/plasmid/rna modes), MEGAHIT (low-memory, huge datasets), Unicycler (bacterial finishing/hybrid), MaSuRCA (large hybrid), ABySS (Bloom-filter), and Platanus (heterozygous diploids), using multi-k de Bruijn graphs. Covers the repeat-resolution limit, why N50 plateaus at the genome not the depth, GenomeScope2 k-mer profiling first, the heterozygosity/haplotig trap, error-correction erasing rare alleles, GC dropout, and NG50/auN/BUSCO reporting. Use when assembling a bacterial isolate, fungal, small-eukaryotic, single-cell, or metagenome genome from Illumina reads, or when deciding whether short reads can even produce the assembly being asked for.

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Compare cell-type composition and spatial features across conditions in IMC/MIBI cohorts with the patient as the experimental unit, covering pseudoreplication, per-patient aggregation, mixed models, compositional (Dirichlet/scCODA) differential abundance, diffcyt, per-image-to-patient spatial differential testing (SpaceANOVA), batch covariates, and FDR. Use when testing whether a cell type or spatial niche differs between groups, avoiding cell-level pseudoreplication, choosing a differential-abundance method, or correctly powering an IMC cohort comparison.

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Designs and ranks guide RNAs (sgRNAs) for CRISPR-Cas9/Cas12a gene knockout by scanning a target for PAM sites (NGG SpCas9, NNGRRT SaCas9, TTTV Cas12a, NG SpCas9-NG, near-PAMless SpRY), enumerating candidate spacers, applying hard filters (Pol-III TTTT terminator, 5' G, GC), ranking on-target activity with the context-appropriate model (Rule Set 2/Azimuth for U6/lentiviral, CRISPRscan for T7/embryo, DeepHF for high-fidelity variants, DeepCpf1 for Cas12a), and predicting the indel/frameshift outcome (Bae out-of-frame score, inDelphi, FORECasT, Lindel). Use when selecting sgRNAs to knock out a gene, choosing a nuclease/PAM for a constrained locus, picking which exon to target, or shortlisting guides before an off-target check. Off-target specificity, base/prime editing, and HDR donors are separate skills.

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Rank and prioritize neoantigen/epitope candidates by likely T-cell response using NeoFox feature annotation, PRIME2.0, BigMHC-IM, the Łuksza/Balachandran fitness model (agretopicity + foreignness), and pVACtools tiering. Encodes the field's hard truths that immunogenicity is the least-solved layer (dedicated scores ~AUROC 0.6-0.7, modest PPV), that scores are valid only for RANKING within one patient (never absolute go/no-go or cross-patient), that DAI has anchor-inflation and WT-denominator traps, and that stacking weak correlated scores into one number is a red flag. Use when ordering a candidate list for a vaccine. Binding lives in mhc-binding-prediction; calling in neoantigen-prediction.

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Decides whether and how to polish a draft genome assembly to raise consensus accuracy (QV) with read-type-matched tools - Racon and medaka (ONT consensus), dorado polish, Polypolish and pypolca (Illumina, repeat-aware), Pilon (legacy short-read), NextPolish/NextPolish2, Hapo-G (haplotype-aware), ntEdit, and DeepPolisher/PEPPER-Margin-DeepVariant for human. Covers the do-not-polish-HiFi rule, the medaka basecaller-model footgun, held-out Merqury QV as the only honest stop signal, and the haplotype-collapse trap. Use when correcting homopolymer indels or residual SNPs in a long-read assembly, deciding if a HiFi assembly needs polishing, or choosing an ONT vs hybrid vs short-read polishing chain.

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Parses, queries, converts, and extracts from GTF and GFF3 gene-model annotation files - walking the gene/transcript/exon/CDS hierarchy with gffutils (queryable SQLite DB), converting formats and extracting transcript/CDS/protein FASTA with gffread, slurping to dataframes with gtfparse/pyranges, and sanitizing malformed files with AGAT. Covers the 1-based-inclusive vs 0-based BED coordinate conversion (start-1 only), deriving implicit features (introns/UTRs/TSS), phase-not-frame, the stop-codon-in-or-out-of-CDS convention, and the chr1-vs-1 seqid and gene-ID-version mismatches that silently produce all-zero count matrices and dropped joins. Use when extracting features or sequences from an annotation, converting GTF<->GFF3 or GTF->BED, traversing the gene tree, or diagnosing a coordinate/provenance mismatch upstream of counting or DE.

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Infer transcription factor regulons from single-cell RNA-seq with pySCENIC by combining GRNBoost2 co-expression, cisTarget motif-enrichment pruning, and AUCell per-cell activity scoring. Covers the motif-pruning-as-directionality principle, regulon specificity scoring, run-to-run stability, and database/species matching. Use when identifying TF regulons, scoring TF activity per cell, finding master regulators of cell identity, or comparing regulon activity across conditions. For enhancer-driven multiomic GRNs see multiomics-grn; for bulk inference and VIPER protein-activity see grn-inference.

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Transfers gene annotations between genome assemblies via coordinate liftover (UCSC liftOver, CrossMap for same-species version updates) or feature/sequence projection (Liftoff for same/close species, miniprot for protein-level cross-species, TOGA/GeMoMa/CAT for distant clades). Covers the coordinate-vs-projection decision by divergence, why a successful lift is not biological confirmation, reference bias, the silent-dropping of unmapped features, build/PAR/MHC/inversion hazards, and transfer-vs-de-novo validation. Use when annotating a new assembly of a species with an existing reference, harmonizing coordinates across builds, or mapping annotations across related species.

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Infers person-to-person transmission from pathogen genomes using outbreaker2 (Campbell 2018), TransPhylo (Didelot 2017), phybreak (Klinkenberg 2017), BadTrIP (De Maio 2018), SCOTTI (De Maio 2016), BEASTLIER (Hall 2015), and SNP-distance / cluster-picker approaches (HIV-TRACE for HIV; transcluster). Defines outbreak clusters using pathogen-specific SNP thresholds (NOT a universal cutoff -- TB <=12 SNPs / Walker 2013; MRSA <=15 / Coll 2017; C. difficile <=2 / Eyre 2013; Klebsiella <=21 / Snitkin 2012), models within-host diversity and transmission bottlenecks (Worby-Lipsitch-Hanage 2014; McCrone 2018; Sobel Leonard 2017; Lythgoe 2021 SARS-CoV-2), integrates contact-tracing data, distinguishes generation interval from serial interval (Britton & Scalia Tomba 2019; Ali 2020), attributes source via Bayesian source attribution (Mather 2013 DT104; islandR), and reconciles transmission-network reconstruction with epi metadata. Use when investigating outbreaks for who-infected-whom, defining SNP-cluster outbreak definitions, accounting for unsampled intermediates, choosing between outbreaker2 (rich epi data) and TransPhylo (genomic-only after dated phylogeny), running source attribution between host populations, calling HIV-TRACE thresholds appropriate to the local subtype, or distinguishing recent transmission from reactivation in TB / chronic HIV.

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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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Estimates the minimum biological replicates (or cells/events) for a target power at a target FDR in genomics experiments using ssizeRNA, PROPER, powsimR for scRNA-seq, and pilot-data dispersion estimation from DESeq2/edgeR. Covers the biological-versus-technical replication distinction (technical replicates do not add degrees of freedom for biological inference), replicate-number-versus-sequencing-depth budgeting, scRNA-seq sample-versus-cell allocation under a pseudobulk model, and the critique that "n=3" is a publication convention rather than a power calculation. Use when budgeting a sequencing experiment, writing the sample-size justification in a grant, estimating replicates from pilot data, allocating a fixed budget between samples and depth, or planning scRNA-seq cohort size. For clinical-trial sample size see clinical-biostatistics/power-and-sample-size; for the power-given-n direction see experimental-design/power-analysis.

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Differential abundance (DA) and differential state (DS) analysis for flow and mass cytometry - tests which cell populations change in frequency or marker expression between conditions using diffcyt (edgeR/voom/GLMM for DA, limma/LMM for DS), with cydar, CITRUS, and compositional methods (sccomp, scCODA, DCATS) as alternatives. Covers the sample-is-the-experimental-unit principle, design/contrast and mixed-model formulas, compositionality of cluster proportions, and FDR across clusters. Use when comparing populations between groups, choosing a DA method, handling paired/batch designs, or deciding whether compositional correction is needed.

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Identifies differential m6A methylation between conditions from MeRIP-seq paired IP/input data using exomePeak2 with `bam_ip` + `bam_input` (control arm) and `bam_treated_ip` + `bam_treated_input` (treatment arm) for integrated GC-bias-aware differential calling (Liu 2022 *NAR Genom Bioinform* 4:lqac046), QNB beta-binomial test (Liu 2017 *BMC Bioinformatics* 18:387), MeTDiff HMM-based differential bundled with MeTPeak, RADAR (Zhang 2019 *Genome Biol* 20:294) with its `filterBins -> diffIP -> reportResult` workflow, and the defensible paired-symmetric case of edgeR / DESeq2 on featureCounts-on-peaks matrices when batch / lot covariates need explicit fixed-effect handling (exomePeak2's top-level API does NOT accept arbitrary covariates). Covers paired vs unpaired vs interaction designs, batch confounding (antibody lot, RNA prep, sequencing run) and the per-lot meta-analysis strategy when exomePeak2 is the primary caller, the stoichiometry-vs-expression-vs-IP-efficiency confound that all MeRIP differential methods inherit, normalisation choice (size factor on IP, on input, on per-sample IP/input ratio), the McIntyre 2020 reproducibility caveat, effect-size filtering as a guardrail against under-powered N=2 designs, and orthogonal-validation routes for absolute stoichiometry (GLORI / SAC-seq / m6Anet `mod_ratio`). Use when comparing m6A levels across two or more conditions, choosing between exomePeak2 / QNB / RADAR / MeTDiff for a given design, handling batch confounding when exomePeak2's API is too rigid, normalising against input properly, distinguishing real hyper- / hypo-methylation from expression-level shifts, applying effect-size thresholds, interpreting volcano plots of differential peaks, or planning a follow-up orthogonal stoichiometry validation.

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Simulate transcription factor perturbation effects on cell state in silico with CellOracle and Dynamo, and predict transcriptional responses to genetic perturbations with GEARS, scGen, and CPA. Covers the direction-not-magnitude principle, local-linear validity, the GRN/velocity error it inherits, baseline discipline (mean and additive baselines), and the validation gap. Use when predicting TF knockout or overexpression effects, ranking driver TFs for fate transitions, or planning perturbation experiments. For GRN construction see multiomics-grn; for experimental Perturb-seq see single-cell/perturb-seq.

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Aligns sample metadata with count matrices and constructs design matrices for downstream DE, handling the alphabetical-reference-level trap (relevel BEFORE DESeq), LRT reduced-model rules, the interaction-term resultsNames trap, continuous-covariate scaling and splines, repeated measures via duplicateCorrelation or dream, high-cardinality categorical pseudo-singular designs, sample swap detection via XIST/RPS4Y1 expression and somalier/NGSCheckMate genotypes, SABV (sex-as-biological-variable) mandate, Simpson's-paradox collapsing of technical replicates, and the `~ 0 + group` parameterization for clean contrasts. Use when building a design matrix, troubleshooting reversed fold-change direction, encoding paired or repeated-measures designs, detecting sample swaps, deciding sex-as-covariate, or aggregating technical replicates.

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Quality control for flow, spectral, and mass cytometry - time-based anomaly cleaning (flowAI, flowCut, PeacoQC, flowClean), margin/boundary event removal, signal-drift detection, dead-cell exclusion, CyTOF Gaussian/DNA/event-length checks, instrument calibration/standardization (MESF, CS&T, peak-2), and batch-level outlier flagging. Use when assessing acquisition quality, choosing a cleaning tool, ordering QC relative to compensation, deciding margin removal before density-based steps, or flagging problematic samples before clustering or differential analysis.

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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.

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Analyzes time-series and longitudinal RNA-seq for differential expression and trajectory structure. Covers DESeq2 LRT with reduced models, time as factor vs continuous vs natural splines, maSigPro (Nueda 2014 for RNA-seq), ImpulseDE2 with explicit impulse-model failure modes, DREAM for repeated measures via linear mixed models, pseudoreplication avoidance, conditional vs marginal modeling, and trajectory clustering with DPGP, Mfuzz (with Schwämmle 2010 fuzzifier estimation), and splines+k-means. Use when modeling time-course or longitudinal expression, choosing factor vs spline, handling repeated measures from the same subject, avoiding pseudoreplication, clustering temporal trajectories, or selecting between dedicated time-course tools and pairwise+LRT.

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Infer gene regulatory networks from bulk or general expression data with mutual-information (ARACNe) and tree-ensemble (GENIE3, GRNBoost2) methods, and infer transcription-factor protein activity from regulons with VIPER and msVIPER. Covers the activity-not-edges paradigm, the undirected-association caveat, the DREAM5 wisdom-of-crowds and method-complementarity result, AUPRC-over-AUROC evaluation, and gold-standard incompleteness. Use when inferring a regulatory network from a bulk expression matrix, finding master regulators, or scoring TF activity from a signature. For single-cell motif-pruned regulons see scenic-regulons; for co-expression modules see coexpression-networks.

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Quantifies biodiversity from species abundance/incidence tables using Hill numbers (iNEXT) with coverage-based rarefaction-extrapolation (Chao & Jost 2012), asymptotic richness via Chao1/ACE/jackknife as a lower bound, Baselga turnover/nestedness partition with the Podani alternative as sensitivity check, mandatory Hellinger transformation before ordination (Legendre & Gallagher 2001), Faith PD and SES_MPD/SES_MNTD with explicit null-model choice, and Maire 2015 functional-diversity dimensionality optimization. Use when comparing diversity across sites with unequal sampling effort, picking the right richness estimator for singleton-heavy amplicon data, partitioning beta diversity into turnover vs nestedness, reporting Hill-number effective species counts rather than raw entropies, computing SES_MPD with explicit null-model justification, or deciding whether to apply standard metrics to compositional amplicon data. Not for clinical 16S microbiome diversity (see microbiome/diversity-analysis).

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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.

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Build enhancer-driven gene regulatory networks (eGRNs) by integrating single-cell RNA-seq and ATAC-seq using SCENIC+, CellOracle base GRNs, Pando, FigR, DIRECT-NET, TRIPOD, and scMEGA. Covers the accessibility-defines-enhancers principle, peak-to-gene linking and its cell-composition confound, the paired-vs-unpaired decision, and TF-region-gene eRegulon triplets. Use when analyzing 10x multiome or paired/unpaired scRNA+scATAC to infer cis-regulatory GRNs. For RNA-only regulons see scenic-regulons; for in silico TF perturbation see perturbation-simulation.

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Download raw sequencing reads from NCBI SRA using sra-tools (prefetch, fasterq-dump, vdb-validate) or the ENA mirror. Use when pulling FASTQ for SRR/ERR/DRR accessions, deciding between SRA-direct, ENA mirror, or AWS/GCP cloud mirror (STRIDES), handling --include-technical for 10x and other single-cell records, validating with MD5/vdb-validate, navigating SRR/SRX/SRS/SRP/PRJNA hierarchy, or finding accessions via pysradb. Encodes SRA cloud-egress economics, the fasterq-dump uncompressed-scratch trap, and the --max-size default that silently truncates large prefetches.

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