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Processes environmental DNA metabarcoding data from raw amplicon reads to species occurrence tables using OBITools3, DADA2, and taxonomic assignment against BOLD, MIDORI2, or MitoFish databases. Handles COI, 12S, rbcL, and ITS barcode regions with primer removal, denoising, chimera detection, and contamination filtering via decontam. Includes occupancy modeling (occumb) for detection probability correction. Use when analyzing eDNA from water, soil, or bulk samples for biodiversity monitoring. Not for 16S human microbiome (see microbiome/amplicon-processing).

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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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Detect and remove doublets from flow and mass cytometry data. Covers FSC/SSC gating and computational doublet detection methods. Use when filtering out cell aggregates before clustering or quantitative analysis.

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Analyzes CRISPR drug-modifier (chemogenomic) screens with drugZ (Li & Hart 2019 Genome Med), a bidirectional Z-score method that identifies synthetic-lethal sensitizing genes and resistance-conferring suppressor genes from vehicle vs drug comparisons. Covers vehicle-anchored design (not Day-0), the bidirectional Z math giving 2-3x sensitivity over MAGeCK / STARS / edgeR / RIGER on drug screens, per-gene sumZ and normZ, synth (sensitizer) vs supp (suppressor) FDR, multi-dose handling, integration with control sgRNAs, and comparison with MAGeCK MLE with dose covariate. Use when running a drug-modifier CRISPR screen, identifying sensitizing or resistance genes for a drug candidate, choosing drugZ vs MAGeCK MLE for chemogenomic analysis, troubleshooting low-effect drug screens where MAGeCK lacks sensitivity, or designing a drug-screen layout (vehicle vs drug arms).

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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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Find cross-database references between NCBI databases using Biopython Bio.Entrez (ELink). Use when navigating gene to protein/structure, sequence to publication, PubMed to GEO, BioProject to SRA runs, or discovering all link relationships for a record. Covers linkname semantics, cmd= variants, asymmetric link warnings, neighbor_history for >200 input IDs, and per-database link tables.

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End-to-end eDNA metabarcoding from raw amplicons to community ecology. Covers QC, primer removal, denoising with OBITools3 or DADA2, contamination filtering, taxonomy assignment, Hill number diversity, and constrained ordination. Use when processing environmental DNA samples for biodiversity assessment or ecological surveys.

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Comprehensive variant filtering including GATK VQSR, hard filters, bcftools expressions, and quality metric interpretation for SNPs and indels. Use when filtering variants using GATK best practices.

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Analyzes cfDNA fragment size distributions and fragmentomics features using FinaleToolkit or Griffin. Extracts nucleosome positioning patterns, fragment ratios, and DELFI-style fragmentation profiles for cancer detection. Use when leveraging fragment patterns for tumor detection or tissue-of-origin analysis.

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Perform flux balance analysis (FBA) and flux variability analysis (FVA) on genome-scale metabolic models using COBRApy. Predict growth rates, metabolic fluxes, and optimal resource utilization. Use when predicting metabolic phenotypes or optimizing flux distributions.

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Predict enhancer-gene regulatory connections from ATAC-seq using ABC, ENCODE-rE2G, HiChIP, or Cicero. Use when linking distal enhancers to target genes, choosing between contact-aware (ABC, ENCODE-rE2G), accessibility-only (Cicero), and orthogonal (HiChIP H3K27ac, EpiMap) approaches, validating predictions against CRISPRi-FlowFISH gold-standard, or building cell-type-specific regulatory maps for fine-mapping or therapeutic target discovery.

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Visualize enrichment results using enrichplot package functions. Use when creating publication-quality figures from clusterProfiler results. Covers dotplot, barplot, cnetplot, emapplot, gseaplot2, ridgeplot, and treeplot.

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Perform differential expression analysis using edgeR in R/Bioconductor. Use for analyzing RNA-seq count data with the quasi-likelihood F-test framework, creating DGEList objects, normalization, dispersion estimation, and statistical testing. Use when performing DE analysis with edgeR.

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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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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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Select restriction enzymes by criteria using Biopython Bio.Restriction. Find enzymes that cut once, don't cut, produce specific overhangs, are commercially available, or have compatible ends for cloning. Use when selecting restriction enzymes for cloning or analysis.

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Maps GWAS-implicated loci to candidate effector (causal) genes by integrating variant-to-gene (V2G) features via Open Targets L2G (Mountjoy 2021), MAGMA gene-based association (de Leeuw 2015), FUMA SNP2GENE, cS2G combined SNP-to-gene scores (Gazal 2022), Polygenic Priority Scores (PoPS, Weeks 2023), FLAMES, INQUISIT, DEPICT, and enhancer-gene predictors (ABC, ENCODE-rE2G). Use when narrowing a GWAS lead locus to a candidate causal gene, picking between proximity, eQTL-based, and similarity-based prioritizers, integrating multi-evidence streams (fine-mapping, colocalization, ABC enhancer-gene, distance, chromatin), reconciling discordant L2G vs PoPS calls, prioritizing tissue-specific eQTL evidence, or triangulating across at least three independent lines of evidence for a publication-grade effector-gene nomination.

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Workflow from differential expression results to functional enrichment analysis. Covers GO, KEGG, Reactome enrichment with clusterProfiler and visualization. Use when taking DE results to pathway enrichment.

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Performs alchemical free-energy calculations including relative binding free energy (RBFE / FEP+) and absolute binding free energy (ABFE) via OpenFE, FEP+, GROMACS, AMBER pmemd, and OpenMM with explicit lambda window scheduling, soft-core potentials, REST2 enhanced sampling, MBAR/BAR analysis, and cycle closure validation. Compares ML alternatives (Boltz-2 affinity, DeepDock). Use when ranking analogs by binding affinity beyond docking accuracy, performing prospective lead optimization, or validating SAR predictions.

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Mark and remove PCR/optical duplicates using samtools fixmate and markdup. Use when preparing alignments for variant calling or when duplicate reads would bias analysis.

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Exports publication-ready figures in various formats with proper resolution, sizing, and typography. Use when preparing figures for journal submission, creating vector graphics for presentations, or ensuring consistent figure styling across analyses.

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Filter and select sequences by criteria (length, ID, GC content, patterns) using Biopython. Use when subsetting sequences, removing unwanted records, or selecting by specific criteria.

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Computes and interprets treatment effect measures (OR, RR, RD, HR, NNT) with calibrated confidence intervals (Wilson, Newcombe, Miettinen-Nurminen, MOVER, profile likelihood, Bender NNT) and reports marginal vs conditional estimands per FDA 2023 covariate adjustment guidance. Use when reporting treatment effects in confirmatory trials, comparing effect sizes across studies, or constructing forest plots.

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Predict B-cell and T-cell epitopes using BepiPred, IEDB tools, and structure-based methods for vaccine and antibody design. Identify immunogenic regions in antigens. Use when designing vaccines, mapping antibody binding sites, or predicting immunogenic peptides.

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