Tangermeme is a PyTorch library for post-training interpretability of sequence-based deep learning models in regulatory genomics. It provides a comprehensive suite of functions for analyzing what a trained model has learned about cis-regulatory elements, including attribution methods (DeepLIFT/SHAP, saturation mutagenesis, PISA), sequence perturbation experiments (marginalization, ablation, variant effect, spacing analysis), motif discovery via seqlet calling (recursive and TF-MoDISco-style), and sequence design (greedy/beam search substitution). The library is designed to be assumption-free, extensible to any alphabet, and works with any PyTorch model that operates on one-hot encoded sequences. Key entry points are the `deep_lift_shap`, `predict`, `ersatz`, `marginalize`, `ablate`, `seqlet`, `annotate`, and `design` subpackages, all exposed through a consistent API that accepts a `func=` argument for composability. The library includes a built-in Claude Code skill installer for AI-assisted development, extensive unit tests with toy models, and documentation with tutorials and vignettes. Tangermeme is actively developed (semantic versioning, regular releases) and targets bioinformaticians working with models like BPNet, Enformer, Beluga, or ChromBPNet.
AlphaGenome is a Python client library and SDK for interacting with Google DeepMind's AlphaGenome cloud service, a deep learning model that predicts molecular properties (gene expression, splicing, chromatin accessibility, histone marks, contact maps) from DNA sequence. The library provides gRPC-based clients for sequence, interval, and variant prediction, along with precomputed variant scores via the Atlas service. It includes rich data containers (TrackData, JunctionData), modular visualization components (tracks, transcripts, sashimi plots), and interpretation tools like in-silico mutagenesis. The repository also contains a set of Colab notebooks demonstrating end-to-end workflows for variant scoring, haplotype analysis, splicing quantification, and batch processing. The architecture is a thin client layer over a remote API, with protobuf definitions for service contracts and tensor serialization. Core modules handle genomic data types (Interval, Variant, Transcript), gene annotation parsing, ontology mapping, and efficient tensor packing. The variant scoring framework is extensible via dataclass-based scorers (center mask, gene mask LFC, splicing, polyadenylation) and includes utilities to tidy AnnData results into pandas DataFrames. Visualization is component-based, allowing composition of tracks, contact maps, and annotations into publication-quality figures. While primarily an application library, the repo has a strong data research character due to its focus on genomic analysis and the included notebooks. The code is well-structured, with extensive unit tests and CI/CD pipelines. However, it is tightly coupled to the AlphaGenome API and protobuf definitions, limiting standalone reuse. The most reusable components are the data containers (TrackData, JunctionData), tensor packing utilities, and the variant scorer dataclass pattern, which could be extracted for other genomic scoring tasks.
Smudgeplot is a bioinformatics CLI tool for reference-free ploidy inference from whole genome sequencing data. It operates on FastK k-mer databases, identifying heterozygous k-mer pairs (hetmers) using a high-performance C backend, then aggregates them into 'smudges' via a local clustering algorithm in Python. The tool infers haploid coverage through a grid search and produces 2D histogram plots (smudgeplots) that reveal haplotype structure. The codebase is a hybrid of a Python package (command-line interface, data analysis, matplotlib-based visualization) and a custom C library (parallelized k-mer pair detection). It follows a clean architecture with well-separated concerns, a comprehensive CLI, and CI/CD pipelines for distribution. The project is actively maintained, with recent support for Python 3.14 and cross-platform wheel builds.
The Genome Analysis Toolkit (GATK4) is a production-grade bioinformatics framework developed by the Broad Institute for variant discovery and genotyping in high-throughput sequencing data. It provides a comprehensive suite of command-line tools for germline and somatic variant calling (HaplotypeCaller, Mutect2), copy number variation analysis (GermlineCNVCaller), structural variant detection (FindBreakpointEvidenceSpark), functional annotation (Funcotator), base quality score recalibration (BQSR), and read processing. The architecture is built around a plugin-style engine with walker base classes (ReadWalker, VariantWalker, LocusWalker) that define traversal patterns over genomic data, with extensive use of Apache Spark for distributed execution on clusters and cloud platforms (GCS, HDFS). Key entry points include the `gatk` wrapper script and individual tool classes registered via the Barclay argument parser, with workflows orchestrated through WDL/Cromwell pipelines. External dependencies include htsjdk for BAM/VCF I/O, BWA for alignment, PyMC3 for Bayesian CNV modeling, and PyTorch for deep learning-based variant scoring. The codebase is heavily tested with unit and integration tests, and supports both local and cloud-based execution.
This repository is a curated collection of 177+ domain-specific scientific 'skills' for AI agents, following the Agent Skills standard. Each skill is a self-contained module providing a CLI tool, documentation, and tests for a specific scientific or technical task—ranging from single-cell RNA-seq analysis (scanpy) and molecular docking (diffdock) to clinical report validation and ISO standards readiness. The architecture is a monorepo of independent skills, each with its own scripts/, references/, assets/, and tests/. Skills are designed to be safe, bounded, and reproducible: they validate inputs before execution, enforce resource limits, avoid network access unless explicitly required, and produce structured JSON reports. The repository also includes a shared test infrastructure (skill_contract) and a meta-skill (autoskill) that can automatically propose new skills from screen activity. While primarily an application library for AI agents, it has strong data/research characteristics due to its heavy use of scientific data formats and validation of research artifacts.
htsjdk is a comprehensive Java library for reading, writing, and manipulating high-throughput sequencing (HTS) data formats, including SAM, BAM, CRAM, VCF, BCF, FASTQ, FASTA, BED, and GFF3. It provides format-specific codecs, indexing (BAI, CRAI, CSI, Tabix, tribble), block-compressed I/O (BGZF with libdeflate acceleration), and a plugin-based codec registry (beta package). The library is used by major bioinformatics tools like Picard, GATK, and IGV. It includes extensive CRAM compression support (rANS, FQZComp, range coding, name tokenisation) and versioned codec implementations for CRAM 3.0/3.1 and VCF 4.0-4.3. The architecture follows a layered design: low-level I/O streams, format-specific readers/writers, and a higher-level plugin framework for content-type decoupling. While the codebase is actively maintained and well-tested, it contains some deprecated APIs, experimental beta code, and a few unimplemented code paths, reflecting its long evolution and breadth of format support.
PyRanges (version 0, legacy) is a Python library for genomic interval operations, analogous to Bioconductor's GenomicRanges. It provides a comprehensive set of tools for manipulating, comparing, and analyzing genomic intervals and annotations. The library supports reading and writing common bioinformatics file formats (BED, GTF, GFF3, BAM, BigWig), and implements a wide range of operations including merging, intersection, subtraction, join, nearest neighbor, clustering, coverage, and statistical methods like Jaccard and Fisher exact. Internally, PyRanges represents intervals as a dictionary of pandas DataFrames keyed by chromosome and optionally strand. This design enables efficient per-chromosome parallelism and easy integration with the Python data science stack. Operations are implemented as modular functions in separate files under the `methods/` directory, each accepting a DataFrame and keyword arguments from a central dispatcher. The library also provides a parallel execution framework using Ray via `pyrange_apply` and related functions, allowing users to apply custom functions to each chromosome/strand group in parallel. Although primarily a software library, this repository has a strong research character: it includes built-in example datasets (e.g., ChIP-seq peaks, CpG islands, Ensembl annotations), a bookdown tutorial with executable R Markdown, property-based tests that compare results against the bedtools suite, and statistical methods designed for colocalization and annotation enrichment. This makes it equally valuable as a research tool for bioinformatics analysis. Maintenance note: This is the legacy version 0 of PyRanges, superseded by a redesigned version 1 (pyranges1). Despite the deprecation, the codebase is mature, well-tested, and still functional. The design patterns (modular operations, per-chromosome dispatch, property-based testing against a reference tool) are noteworthy and could be reused in other bioinformatics and data engineering projects.
This is an R/Bioconductor package for making enriched heatmaps, primarily used in epigenomics to visualize enrichment of genomic signals (e.g., histone modifications, DNA methylation) around target regions (e.g., transcription start sites). The package provides a workflow: normalize signals to a matrix via `normalizeToMatrix()`, then draw a heatmap with `EnrichedHeatmap()`, which is a subclass of ComplexHeatmap. It includes specialized annotation (`anno_enriched()`), row ordering by enrichment scores, smoothing, and support for categorical signals. The architecture leverages S3 classes (normalizedMatrix) and integrates with GenomicRanges for genomic interval operations. It is well-documented with vignettes and a pkgdown site, and includes Rcpp for performance-critical distance calculations. While the package is actively maintained, there are some signs of technical drift such as deprecated arguments and an old CI configuration.
maftools is an R/Bioconductor package for the analysis and visualization of somatic mutations in cancer genomics, primarily using Mutation Annotation Format (MAF) files. It provides a comprehensive suite of functions for reading, summarizing, and plotting mutation landscapes (oncoplots, lollipop plots, rainfall plots), detecting driver genes, analyzing mutational signatures via NMF, assessing tumor heterogeneity (MATH score), comparing cohorts, and integrating copy number alterations from GISTIC or ASCAT. The package also includes tools for converting other formats (ANNOVAR, ICGC) to MAF, querying cancer hotspots directly from BAM files via a C backend, and detecting sample swaps. It is widely used by cancer researchers and relies on Bioconductor infrastructure, with extensive bundled reference data (COSMIC signatures, cancer hotspots, TCGA burden). While primarily a software library, its heavy use of precompiled research data and domain-specific pipelines gives it a hybrid character. The codebase is well-structured with S4 classes and data.table for performance, though some functions have long parameter lists and a few deprecated modules.
SequenceServer is a Ruby/Sinatra web application that provides a graphical interface for running NCBI BLAST+ and DIAMOND sequence similarity searches against custom databases. It manages BLAST database formatting, job submission with background execution, result parsing, and interactive visualization of alignments using D3.js and Circos-style plots. The backend uses a thread pool for concurrent job processing, YAML-based job persistence, and a plugin system for extensibility. The frontend is built with React and includes components for database selection, query input, and result exploration with export to SVG/PNG. The application is designed for bioinformatics researchers who need a self-hosted BLAST server with a modern web UI, supporting multiple BLAST programs (blastn, blastp, blastx, tblastn, tblastx) and DIAMOND. It includes comprehensive test suites for multiple BLAST versions and CI/CD pipelines for Docker and AppImage deployment.