BWA-MEM2 — DNA Short-Read Aligner

Overview

BWA-MEM2 aligns short DNA reads (Illumina, 50–250 bp) to a reference genome using the BWT-FM index. It is the standard aligner for whole-genome sequencing (WGS), whole-exome sequencing (WES), ChIP-seq, and ATAC-seq DNA alignment. BWA-MEM2 is 2× faster than the original BWA-MEM while producing identical results. It outputs SAM format with proper read group (@RG) headers required by GATK HaplotypeCaller and Picard tools. For paired-end reads, it marks proper pairs and resolves chimeric/split reads into supplementary alignments.

When to Use

• Aligning WGS or WES Illumina reads to a reference genome for variant calling (SNP, indel, SV)
• ChIP-seq or ATAC-seq DNA alignment to produce BAM files for peak calling with MACS3
• Producing GATK-compatible BAM files with @RG read group tags
• Aligning reads ≥ 50 bp; for shorter reads (< 50 bp), BWA-backtrack may be more appropriate
• Re-aligning legacy FASTQ files to an updated reference genome assembly
• Use STAR instead for RNA-seq reads that span splice junctions
• Use Bowtie2 as an alternative for local alignment or when index size must be minimized

Prerequisites