SAMtools

SAMtools is a portable, open-source software suite for interacting with high-throughput sequencing data stored in the SAM (Sequence Alignment/Map), BAM (Binary Alignment/Map), and CRAM formats. It provides a collection of tools for extracting, converting, sorting, indexing, and manipulating alignments, as well as utilities for computing statistics and generating read-depth information. SAMtools is widely used in genomic data processing pipelines to manage large alignment datasets efficiently.

Key programs include samtools view, which can display or convert between SAM and BAM; samtools sort and samtools index for ordering and indexing alignments; samtools flagstat and samtools stats for summary metrics; samtools depth and samtools coverage for per-base depth statistics; samtools merge for combining files; samtools reheader and samtools calmd for metadata and MD tag updates; and samtools tview for interactive text-based visualization. The mpileup command historically provided per-base read data for variant calling and is commonly used with variant callers such as bcftools, which is part of the same software ecosystem.

SAMtools depends on the HTSlib library for input/output and file format support, and is typically used in conjunction with bcftools. It supports indexing with .bai or .csi formats, enabling rapid access to reads from large BAM and CRAM files. It is cross-platform and widely included in bioinformatics distributions and pipelines.

Originating with Heng Li and collaborators, SAMtools has become a de facto standard in the processing of alignment data within the SAM/BAM ecosystem. It is released as free, open-source software under a permissive license and is actively maintained with regular updates.