Pysam

If you're working with genomic data in Python, this is the standard tool for reading and writing alignment files (BAM/CRAM), variant files (VCF/BCF), and reference sequences (FASTA/FASTQ). It wraps htslib so you get the full samtools/bcftools ecosystem with a Pythonic interface. The main thing to watch for is the coordinate system: it uses 0-based half-open intervals except when you pass region strings to fetch(), which are 1-based like samtools. You'll need index files for random access, and the documentation here covers the core workflows like calculating coverage, validating variants against reads, and filtering based on quality metrics. It's mature, well maintained, and handles the file format complexity so you don't have to.

skills.sh installs: 233
GitHub stars: 33.2K
last updated: Aug 21, 2026

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Install

$ npx -y skills add davila7/claude-code-templates --skill pysam --agent claude-code

Installs into .claude/skills of the current project.

Files

Pysam

Overview

Pysam is a Python module for reading, manipulating, and writing genomic datasets. Read/write SAM/BAM/CRAM alignment files, VCF/BCF variant files, and FASTA/FASTQ sequences with a Pythonic interface to htslib. Query tabix-indexed files, perform pileup analysis for coverage, and execute samtools/bcftools commands.

When to Use This Skill

This skill should be used when:

Working with sequencing alignment files (BAM/CRAM)
Analyzing genetic variants (VCF/BCF)
Extracting reference sequences or gene regions
Processing raw sequencing data (FASTQ)
Calculating coverage or read depth
Implementing bioinformatics analysis pipelines
Quality control of sequencing data
Variant calling and annotation workflows

Quick Start

Installation

uv pip install pysam

Basic Examples

Read alignment file:

import pysam

# Open BAM file and fetch reads in region
samfile = pysam.AlignmentFile("example.bam", "rb")
for read in samfile.fetch("chr1", 1000, 2000):
    print(f"{read.query_name}: {read.reference_start}")
samfile.close()

SKILL.md on GitHub