Pysam

If you're processing NGS data, this is the Python wrapper around htslib you'll reach for constantly. It handles SAM/BAM/CRAM alignments, VCF/BCF variants, and FASTA/FASTQ sequences with a clean interface for fetching regions, running pileups, and calculating coverage. The 0-based coordinates take a minute to internalize (except when using region strings, which are 1-based like samtools), but once you do, it's straightforward. You'll need index files for random access, which is standard for this domain. It really shines when you're chaining operations across file types, like validating variants against aligned reads or extracting reference context around mutation sites.

skills.sh installs: 2K
GitHub stars: 56.6K
last updated: Aug 21, 2026

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Install

$ npx -y skills add k-dense-ai/scientific-agent-skills --skill pysam --agent claude-code

Installs into .claude/skills of the current project.

Files

pysam

Overview

Use pysam for low-level, streaming access to HTSlib-supported genomic formats:

AlignmentFile and AlignedSegment for SAM/BAM/CRAM
VariantFile, VariantHeader, and VariantRecord for VCF/BCF
FastaFile for indexed FASTA and FastxFile for sequential FASTA/FASTQ
TabixFile for BGZF-compressed, tabix-indexed BED/GFF/GTF/custom tables
pysam.samtools and pysam.bcftools for wrapped command dispatchers

Current upstream baseline: pysam 0.24.1 (7 September 2026), wrapping HTSlib/samtools/bcftools 1.24. Read references/sources.md before updating version-specific guidance.

Installation

Use the pinned release for reproducible work:

uv pip install "pysam==0.24.1"

Confirm the runtime:

import pysam

print(pysam.__version__)           # 0.24.1
print(pysam.__samtools_version__)  # 1.24

Prebuilt wheels are available for supported macOS and Linux platforms. A source build needs a C compiler and HTSlib build dependencies; read the official installation guide linked from references/sources.md.