「ept」の検索結果

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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Aligns and QCs methylated-RNA-immunoprecipitation (MeRIP / m6A-seq) IP and input libraries using STAR or HISAT2 splice-aware mapping, samtools sort/index, IP/input matched-pair tracking, antibody-lot metadata recording, replicate concordance via deepTools multiBamSummary + plotCorrelation, IP enrichment QC via plotFingerprint and per-transcript IP/input ratio distributions, library-complexity saturation curves via PreSeq c_curve / lc_extrap, and the explicit do-NOT-deduplicate convention for standard non-UMI MeRIP. Use when preparing paired IP and input BAM files for exomePeak2 / MeTPeak / MACS3 peak calling, evaluating MeRIP replicate concordance and IP enrichment, deciding whether to deduplicate (standard MeRIP typically NOT — see Tips), choosing genome-vs-transcriptome alignment for downstream peak vs m6Anet workflows, recording antibody clone and lot metadata for downstream cross-batch reconciliation, detecting failed IPs via saturation curves and IP/input distribution shape, or generating IP-over-Input bigWig tracks for downstream visualisation.

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Estimates time-scaled phylogenies, molecular clock rates, effective reproduction number R_e (or R_t), and population dynamics from dated pathogen genomes using TreeTime (maximum-likelihood) and BEAST2 (Bayesian; strict / uncorrelated lognormal / ORC clocks; constant / exponential / Bayesian Skyline / Skygrid / BICEPS / Birth-Death-Skyline / sampled-ancestor BDSKY priors; structured coalescent via MASCOT). Covers root-to-tip clock signal QC via TempEst, date-randomisation tests (Ramsden 2009; Duchêne 2015), recombination masking via Gubbins and ClonalFrameML before clock inference for recombining bacteria, BDSKY origin-vs-rootHeight pitfalls, sampling-bias correction (Volz & Frost 2014; preferential-sampling extensions), MASCOT structured coalescent for migration, BICEPS-vs-BSP skyline choice, multi-chain BEAST2 convergence diagnostics, and reconciliation between phylodynamic R_e and case-based R_t. Use when dating outbreak origins, estimating substitution rates, inferring R_e through time, building time-calibrated Nextstrain Augur trees, choosing between strict and relaxed clocks, fitting Birth-Death-Skyline (Stadler 2013) models, diagnosing temporal-signal failure, masking recombination before clock inference for *Streptococcus pneumoniae* / *Neisseria gonorrhoeae* / *Klebsiella* / *E. coli* phylodynamics, running MASCOT for structured-population analyses, or using UShER for pandemic-scale placement.

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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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Detects acquired antimicrobial-resistance determinants and chromosomal point-mutation resistance in bacterial assemblies using AMRFinderPlus, ResFinder 4.0 (acquired + PointFinder), CARD-RGI, abritAMR, staramr, and species-specific callers (TB-Profiler, Mykrobe). Harmonises cross-tool output via hAMRonization, contextualises determinants with mobile-genetic-element annotation (MOB-suite, PlasmidFinder, MobileElementFinder, ICEberg), predicts phenotype against EUCAST or CLSI breakpoints, and translates calls into WHO GLASS reporting categories. Use when screening clinical or surveillance isolates for AMR, distinguishing acquired vs intrinsic vs point-mutation resistance, calling rpoB / katG / pncA / gyrA / mgrB mutations, reconciling AMRFinderPlus vs RGI vs ResFinder disagreement, contextualising carbapenemases or mcr alleles on plasmids, predicting susceptibility from genotype against the WHO Mtb 2nd-edition catalogue, or building a hAMRonized multi-lab AMR surveillance pipeline.

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Select colormaps and qualitative palettes for scientific figures using perceptual-uniformity, color-vision-deficiency safety, and luminance-monotonicity criteria. Covers Crameri scientific colormaps, viridis/cividis/magma, Okabe-Ito categorical, ColorBrewer, and the rainbow/jet critique. Use when choosing palettes for heatmaps, scatter, networks, or any encoding where color carries quantitative or categorical meaning.

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Analyzes single-cell pooled CRISPR screens (Perturb-seq, CROP-seq, Perturb-CITE-seq, ECCITE-seq, multiome) where each cell carries an sgRNA and a scRNA-seq / surface-protein / chromatin readout. Covers experimental design (direct-capture Perturb-seq Dixit 2016 vs CROP-seq 3'UTR-barcoded Datlinger 2017 vs ECCITE-seq vs Multiome), MOI for sgRNA assignment, escaper-cell filtering (Mixscape, Papalexi 2021), SCEPTRE NB GLM + permutation for low-MOI (Barry 2024 Genome Biol 25:124), the Pertpy framework, factor decomposition, genome-scale Perturb-seq (Replogle 2022 Cell, 2.5M cells), and per-perturbation single-cell DE. Use when running a single-cell CRISPR screen, choosing direct-capture vs CROP-seq architecture, filtering escaper cells, performing single-cell DE, integrating Perturb-seq with pathway analysis, scaling to GW CRISPRi via Replogle protocol, or analyzing multi-omics screens.

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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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Infer integer allele-specific copy number, tumor purity, and ploidy from tumor sequencing by jointly modeling read depth (logR) and B-allele frequency (BAF) with ASCAT, Sequenza, FACETS, PURPLE, and PureCN (tumor-only). Covers the purity-ploidy identifiability problem, the diploid-baseline (dipLogR) anchor, major/minor copy number, loss of heterozygosity, sunrise/contour fit diagnostics, and reconciliation of conflicting fits. Use when tumor analysis needs absolute copy number rather than relative log2, when estimating purity and ploidy, calling LOH or copy-neutral LOH, resolving whole-genome doubling, running tumor-only allele-specific calling, or choosing among ASCAT, Sequenza, FACETS, and PureCN.

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Visualize copy number profiles, segments, allele-specific tracks, and cohort patterns from CNVkit, GATK, ASCAT, FACETS, Sequenza, and other callers. Covers genome-wide and per-chromosome log2 scatter plots, B-allele-frequency/minor-allele-fraction tracks, ideograms, cohort heatmaps, circos views, and caller-native plots. Use when creating publication CNV figures, choosing which plot answers a given question, diagnosing a wrong diploid baseline visually, displaying loss of heterozygosity, or deciding what depth-only plots cannot reveal.

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Resolve the architecture of focal oncogene amplifications — extrachromosomal DNA (ecDNA), breakage-fusion-bridge (BFB) cycles, homogeneously staining regions (HSR), and linear amplification — from whole-genome sequencing with AmpliconArchitect, the AmpliconSuite pipeline, and AmpliconClassifier. Covers copy-number seed selection, breakpoint-graph reconstruction, balanced-flow optimization, ecDNA classification, and the limits of depth-only amplification calls. Use when a focal amplification needs structural characterization, when distinguishing ecDNA from chromosomal amplification, suspecting ecDNA-driven oncogene amplification or therapy resistance, or selecting copy-number seeds for amplicon reconstruction.

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Queries PharmGKB / CPIC / DPWG for drug-gene interactions; calls CYP2D6/CYP2C9/CYP2C19/DPYD/TPMT/NUDT15/UGT1A1/SLCO1B1 star alleles and phenotype with PharmCAT, Cyrius (CYP2D6 structural variants), Aldy, Stargazer; applies Caudle 2020 activity-score translation. Use when implementing pharmacogenomic-guided prescribing, applying CPIC vs DPWG guidance, screening HLA risk alleles for ICI / antiepileptics / abacavir, or interpreting compound TPMT+NUDT15 thiopurine risk.

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Estimate 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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Generates 3D conformer ensembles using RDKit ETKDGv3 with knowledge-enhanced distance geometry, MMFF94/UFF force-field optimization, CREST + GFN2-xTB semi-empirical refinement, and macrocycle-aware torsion preferences. Provides explicit decision rules for single vs ensemble conformer use, RMSD pruning, energy windows, conformer count, and force-field choice. Use when preparing 3D ligands for docking, generating descriptor input for 3D QSAR, or sampling macrocycle/peptide conformational ensembles.

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Designs PROTACs, molecular glues, and bivalent degraders with explicit handling of E3 ligase choice (VHL, CRBN, IAP, MDM2, KEAP1), linker design (length, composition, rigidity), ternary complex prediction (PRosettaC, DeepTernary, AlphaFold3 with constraints), cooperativity (alpha), DC50 / Dmax characterization, hook effect, and prediction-experiment reconciliation. Use when designing targeted protein degraders, planning linker SAR, predicting ternary complex stability, or building generative degrader workflows.

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Performs structure-based virtual screening using AutoDock Vina, SMINA, GNINA (CNN scoring), and DiffDock-L hybrid workflows with explicit choice rules across rigid vs flexible docking, cross-docking vs self-docking, binding-site detection (P2Rank, fpocket), receptor preparation (PDB2PQR, PROPKA), ligand preparation (meeko, OpenBabel), and ultralarge-library screening (ZINC22, Enamine REAL). Use when screening chemical libraries against a protein target to find candidate binders, ranking docking poses, or selecting a docking workflow for a specific scenario.

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Trains and applies base-resolution deep learning models on ChIP-seq / ChIP-nexus / CUT&RUN data. Uses BPNet (Avsec 2021 Nat Genet 53:354; soft motif syntax from ChIP-nexus), chromBPNet (Pampari A et al 2025 Nat Genet; bias-factorized base-resolution profiles), EnFormer (Avsec 2021 Nat Methods 18:1196; 196 kb input, ~100 kb effective receptive field), DeepSEA (Zhou 2015; multi-task CNN), and JASPAR 2026 deep-learning collection (1259 BPNet ChIP models). Performs in silico mutagenesis for variant-effect prediction, DeepLIFT/Grad attribution, and TF-MoDISco motif discovery from attribution scores. Use when predicting variant effects on TF binding, discovering soft motif syntax / cooperativity, integrating ChIP-seq with sequence-only predictions, or applying precomputed JASPAR Deep Learning models to new variants.

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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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Visualizes ChIP-seq data using deepTools (computeMatrix, plotHeatmap, plotProfile, bamCoverage, bamCompare), pyGenomeTracks (modern INI-driven track plots), Gviz (R browser-style), EnrichedHeatmap (ComplexHeatmap-based), ChIPseeker tag heatmaps, and IGV batch screenshots. Handles bigWig normalization choices (CPM, BPM, RPGC, spike-in scaled), bamCompare operations (log2 ratio, subtract, SES), k-means clustering of heatmaps for biological subgrouping, and spike-in-scaled tracks for global-shift experiments. Use when generating publication-quality ChIP-seq signal heatmaps, profile plots, genome-browser tracks, or comparing samples visually.

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Analyzes CUT&RUN (Skene Henikoff 2017) and CUT&Tag (Kaya-Okur 2019) chromatin profiling data. Handles SEACR vs MACS2 peak calling (with the btaf375 2025 benchmark guidance), pA-MNase vs pA-Tn5 vs pAG-Tn5 chimera differences, E. coli spike-in carryover normalization, IgG-only control logic (no input), characteristic fragment-size signatures (25-75 bp for CUT&Tag), and lower depth requirements (5M reads typical vs 25M for ChIP). Use when calling peaks from CUT&RUN/CUT&Tag, scaling by E. coli spike-in carryover, choosing SEACR norm mode, or comparing CUT&RUN/Tag results to traditional ChIP.

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Calls ChIP-seq peaks with MACS3, MACS2, HOMER, or SPP across narrow (TF) and broad (histone) modes. Handles input control matching, fragment-size modeling vs --nomodel, effective genome size, ENCODE-style IDR vs naive overlap, hyper-ChIPable artifacts, and aligner-specific shifts. Use when calling peaks from ChIP-seq alignments, choosing between narrow vs broad mode for a histone mark, deciding model vs nomodel for low-depth data, applying ENCODE pseudoreplicate IDR, or reconciling MACS vs HOMER vs SPP results.

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Reads, writes, and converts molecular file formats (SMILES, InChI, SDF V2000/V3000, MOL2, PDB, MMTF) using RDKit and Open Babel with rigorous handling of aromaticity perception, stereochemistry, implicit/explicit hydrogens, kekulization, and salt/fragment separation. Use when loading chemical libraries, debugging parse failures, or preparing molecules for downstream standardization, descriptor calculation, or docking.

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ATAC-seq library quality control -- TSS enrichment, FRiP, fragment-size periodicity, library complexity (NRF/PBC1/PBC2), mitochondrial fraction, and ENCODE 4 thresholds. Use when assessing whether an ATAC-seq library passes ENCODE acceptance criteria, diagnosing transposition artefacts, comparing Omni-ATAC vs standard prep quality, or selecting which replicates to drop before peak calling.

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Use this skill when the user asks about CMV maintenance program requirements under 49 CFR 396.3 — what records must be kept, retention periods (12-18 months on vehicle file + 1 year after disposal), what counts as systematic inspection/repair/maintenance, preventive maintenance scheduling, brake adjustment records, and what auditors look for in vehicle files. Cite 49 CFR 396.3 + 396.21.

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