'hpc' 검색 결과

Stores and operates on sparse expression matrices for single-cell and large bulk RNA-seq, covering dgCMatrix/dgRMatrix/dgTMatrix when-each-is-fast, the dgCMatrix (CSC, R) <-> CSR (Python) implicit transpose, AnnData (cells-rows) <-> SingleCellExperiment (cells-cols) orientation flip, HDF5/h5ad vs Zarr cloud-native shift, HDF5SummarizedExperiment + DelayedArray for out-of-memory bulk, scanpy backed mode for large h5ad, the ~10-15% density crossover where dense beats sparse, 10X format proliferation (MTX vs CellRanger H5 vs h5ad), the dense-conversion memory blow-up, and Dask + Zarr for consortium-scale matrices. Use when choosing sparse format, working with single-cell-sized matrices, importing/exporting 10X, debugging R/Python interop transposes, processing matrices too large for RAM, or building cloud-native pipelines.

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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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Bead-based signal normalization and cross-batch harmonization for CyTOF and high-parameter cytometry - EQ four-element bead normalization of instrument sensitivity drift (CATALYST normCytof, premessa), and reference-anchor cross-batch normalization (CytoNorm, per-cluster quantile splines). Covers the distinction between within-run drift correction and between-batch correction, the mandatory anchor/reference sample, why normalization is per-cluster with many quantiles, and the over-correction risk. Use when correcting CyTOF signal drift, harmonizing multi-batch or multi-site studies, or deciding whether to normalize data versus model batch in the design.

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Unsupervised clustering and cell-type identification for high-dimensional flow, spectral, and mass cytometry - FlowSOM, PhenoGraph, FlowSOM-via-CATALYST, with UMAP/tSNE for visualization. Covers the type-vs-state marker distinction (cluster on lineage, test state within clusters), over-provision-then-metacluster, the Weber-Robinson benchmark, seed dependence and metacluster stability, why embeddings are for looking not measuring, and median-heatmap annotation/merging. Use when discovering populations without predefined gates, choosing a clustering algorithm, selecting the number of metaclusters, or annotating clusters into cell types.

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Corrects fluorophore spillover (conventional compensation) or spectral overlap (spectral unmixing) and applies variance-stabilizing transforms (logicle/biexponential, arcsinh, log) for flow and mass cytometry. Covers spillover-matrix estimation from single-stain controls, AutoSpill, the spillover spreading matrix and why panel design (not compensation) bounds resolution, compensate-then-transform ordering, and arcsinh cofactor choice (5 for CyTOF, ~150 for fluorescence, per-channel via flowVS). Use when correcting spectral overlap, preparing data for gating/clustering, choosing logicle vs arcsinh, deciding a cofactor, or distinguishing compensation from spectral unmixing.

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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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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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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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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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Assigns isolate identity at the right resolution for the question -- ANI / Mash species triage, 7-locus MLST historical comparability, cgMLST / wgMLST outbreak resolution (chewBBACA, BIGSdb, Ridom SeqSphere, EnteroBase HierCC), in-silico serotyping (SISTR, SeqSero2 for Salmonella; SerotypeFinder for E. coli; Kaptive K/O for Klebsiella; SeroBA for pneumococcus; spa + SCCmec for S. aureus), and lineage callers (TB-Profiler / Mykrobe Coll-Napier barcode for MTBC, Pangolin + Nextclade for SARS-CoV-2, PopPUNK GPSC for S. pneumoniae). Use when typing bacterial isolates for surveillance or outbreak investigation, choosing between cgMLST allele distance and core-SNP distance for cluster definition, harmonising calls across schemas / database versions (chewBBACA vs Ridom vs EnteroBase), assigning MTBC lineage with the Napier 2020 90-SNP barcode, calling Salmonella serovar via SISTR with monophasic Typhimurium awareness, running Pangolin UShER mode with explicit pangolin-data version pinning, or selecting a typing resolution to match the surveillance question.

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Detects and removes doublets/aggregates from flow, spectral, and mass cytometry before clustering or quantification. Covers FSC-A vs FSC-H singlet discrimination (the Area-Height non-proportionality, not a 1D area gate), FSC-W/SSC width gating, CyTOF Gaussian discrimination parameters (Center/Offset/Width/Residual/Event_length) and DNA intercalator gating, and the residual heterotypic conjugates that survive scatter gating and masquerade as double-positive populations. Use when filtering aggregates before phenotyping, choosing a doublet method for flow vs CyTOF, or diagnosing a suspicious double-positive cluster.

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Reads, inspects, and writes Flow Cytometry Standard (FCS) files from conventional, spectral, and mass cytometry (CyTOF), and parses FlowJo/Cytobank/Diva workspaces. Covers FCS 2.0/3.0/3.1/3.2 internals ($PnE linear-vs-log, $DATATYPE, $SPILLOVER vs SPILL vs $COMP, $TIMESTEP), channel/parameter metadata, the silent linearize/truncate defaults, and R (flowCore, flowWorkspace, CytoML) plus Python (FlowKit, readfcs) readers. Use when loading flow or mass cytometry data, mapping detector channels to antibodies, extracting the event matrix, choosing a reader, or bridging FCS to the scanpy/AnnData ecosystem before preprocessing.

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Defines cell populations in flow and spectral cytometry through manual gates (rectangle, polygon, quadrant, boolean) and reproducible automated gating (openCyto gating templates, flowDensity data-driven thresholds, flowClust model-based gates), organized as a hierarchical GatingSet (flowWorkspace) and round-tripped with FlowJo via CytoML. Covers the canonical gate order (time -> debris -> singlets -> live -> lineage), FMO-vs-isotype boundary setting, gate-order dependence and recompute semantics, rare-event/MRD gating, and per-population statistics. Use when building a gating strategy, automating a manual FlowJo scheme across samples, choosing manual vs data-driven gates, or extracting population frequencies.

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Assesses genetic health of populations for conservation with Ne estimation across time horizons (LDNe NeEstimator V2 option-file API + SNeP physical-linkage correction; recent trajectory via GONE/GONE2; deep history via Stairway Plot 2 / dadi / fastsimcoal2 / PSMC), F-statistics, runs of homozygosity binned by length class to date inbreeding, genetic-load decomposition (Bertorelle 2022 realized vs masked), the modern 100/1000 Ne rule (Frankham 2014), Ne/Nc 2-6 orders of magnitude in marine fish (Hauser & Carvalho 2008), tree-sequence forward simulations (SLiM 4 + pyslim + tskit), and the Sukumaran-Knowles caveat against MSC methods for management-unit definition. Use when estimating Ne by time horizon, detecting inbreeding via F_ROH, decomposing genetic load, justifying conservation thresholds, distinguishing ESU/MU/DPS, configuring NeEstimator V2, or correcting LDNe physical linkage.

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Build weighted gene co-expression networks to identify modules of co-regulated genes, relate them to phenotypes, and find hub genes using WGCNA, hdWGCNA, MEGENA, CEMiTool, and Gaussian graphical models. Covers signed-network choice, soft-threshold selection, module preservation, and the marginal-vs-partial-correlation distinction. Use when finding co-expression modules, identifying hub genes, relating gene networks to clinical or experimental traits, or building single-cell co-expression networks. For directed TF-target inference see scenic-regulons and grn-inference; for condition rewiring see differential-networks.

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Compare gene co-expression and regulatory networks between biological conditions to find rewired relationships using DiffCorr, DiffCoEx, DINGO/iDINGO, and CoDiNA. Covers the differential-connectivity-is-not-differential-expression distinction, the pairwise multiple-testing explosion, marginal vs partial (direct) rewiring, and the underpowered-rewiring failure mode. Use when comparing co-expression networks between disease vs control, treatment, or developmental stages, or finding hub genes that rewire without changing mean expression. For single-condition modules see coexpression-networks; for differential expression of means see differential-expression/de-results.

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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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Tests genotype-environment associations and identifies adaptive loci while correcting for the four-confound landscape (structure, demography, background selection, sampling design) using LFMM2 with mandatory K via sNMF cross-entropy elbow (LEA 3), BayPass Core/AUX/C2/IS with Omega covariance matrix, RDA / pRDA for polygenic adaptation (Forester 2018; requires imputed genotypes), OutFLANK with trimmed FST null, pcadapt, gradient forests (Ellis-Smith-Pitcher 2012, NOT mis-cited Ellis-Manel), Capblancq & Forester 2021 RDA Swiss-army-knife, genomic-offset prediction with Lind & Lotterhos 2025 three-regime caveat, Lotterhos-Whitlock sampling optima, Wang & Bradburd 2014 IBD vs IBE, and Circuitscape + ResistanceGA. Use when identifying adaptive loci across gradients, choosing K for LFMM2, deciding among GEA methods, predicting maladaptation with the novel-environment caveat, distinguishing IBD vs IBE, or optimizing sampling design.

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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.

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Search NCBI databases using Biopython Bio.Entrez (ESearch, EInfo, EGQuery, ESpell). Use when finding records by keyword, building reproducible field-qualified queries, navigating the Entrez Query Translator, exploiting the history server for large result sets, handling retmax caps, or interpreting weekly index lag. Covers PubMed, Nucleotide, Protein, Gene, SRA, GEO, Assembly, Taxonomy, ClinVar, dbSNP.

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Build sequence logos from aligned DNA, RNA, or protein motifs using ggseqlogo (R), Logomaker (Python), or WebLogo with explicit bits vs probability encoding, background-frequency correction, custom alphabets, and multi-logo stacking. Use when visualizing motif PWMs (TF binding, splice sites, CRISPR spacers), aligned-position composition, or comparing two motif sets.

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Run remote BLAST searches against NCBI servers using Biopython Bio.Blast.NCBIWWW. Use when identifying unknown sequences, finding homologs, picking the correct BLAST program (blastn/blastp/blastx/tblastn/tblastx/psiblast/megablast/dc-megablast), interpreting Karlin-Altschul E-values, avoiding the max_target_seqs trap (Shah 2019), choosing composition-based statistics, or limiting searches by organism. Covers RID lifecycle, database choice (nt/nr/refseq_select/swissprot), word-size and CBS taxonomy.

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Query the Ensembl REST API for gene/transcript/protein lookup, sequence retrieval, comparative genomics (Compara), variant effect prediction (VEP), regulatory features, and cross-species ortholog/paralog calls. Use when pulling Ensembl-native data (Ensembl Gene IDs, version-pinned releases, archive endpoints for reproducibility), gene/transcript/exon structure with stable IDs, or VEP for variant annotation. Encodes the 15 req/sec rate limit, archive (e110.rest.ensembl.org) for reproducibility, Ensembl divisions (vertebrates / plants / fungi / metazoa / bacteria), and the symbol-vs-ID stability problem.

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Retrieve records from NCBI databases using Biopython Bio.Entrez (EFetch, ESummary). Use when downloading sequences, fetching GenBank/GenPept records, getting document summaries, parsing nested XML, navigating GI deprecation, choosing between rettype+retmode combinations, and parsing into Biopython SeqRecord/SwissProt objects. Covers nucleotide, protein, gene, pubmed, sra, gds, taxonomy, snp, clinvar.

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