BWA is a fast and accurate short read aligner based on the Burrows-Wheeler Transform (BWT), designed for efficient alignment of short sequencing reads against large reference sequences like the human genome. It supports both base space and color space reads, allowing for mismatches and gaps. BWA is approximately 10–20 times faster than MAQ while maintaining similar accuracy. It outputs alignments in the SAM format, enabling downstream analyses with SAMtools. BWA uses a backward search approach with BWT to efficiently find SA intervals for exact and inexact matches. It reduces memory usage by storing only a fraction of the occurrence and suffix arrays, calculating the rest on the fly. BWA also supports paired-end mapping and generates mapping quality scores. It handles ambiguous bases and allows for a maximum number of differences in alignments. For SOLiD reads, BWA converts the reference genome to a color space and uses dynamic programming to decode color reads into nucleotide sequences. BWA is evaluated on simulated and real data, showing high accuracy and efficiency. It is faster than MAQ, SOAPv2, and Bowtie, with similar accuracy. BWA supports gapped alignment for single-end reads and is suitable for longer reads with indels. It is memory-efficient and supports multi-threading, making it suitable for large-scale sequencing data. BWA provides accurate and efficient alignment, with the ability to handle various types of reads and reference sequences.BWA is a fast and accurate short read aligner based on the Burrows-Wheeler Transform (BWT), designed for efficient alignment of short sequencing reads against large reference sequences like the human genome. It supports both base space and color space reads, allowing for mismatches and gaps. BWA is approximately 10–20 times faster than MAQ while maintaining similar accuracy. It outputs alignments in the SAM format, enabling downstream analyses with SAMtools. BWA uses a backward search approach with BWT to efficiently find SA intervals for exact and inexact matches. It reduces memory usage by storing only a fraction of the occurrence and suffix arrays, calculating the rest on the fly. BWA also supports paired-end mapping and generates mapping quality scores. It handles ambiguous bases and allows for a maximum number of differences in alignments. For SOLiD reads, BWA converts the reference genome to a color space and uses dynamic programming to decode color reads into nucleotide sequences. BWA is evaluated on simulated and real data, showing high accuracy and efficiency. It is faster than MAQ, SOAPv2, and Bowtie, with similar accuracy. BWA supports gapped alignment for single-end reads and is suitable for longer reads with indels. It is memory-efficient and supports multi-threading, making it suitable for large-scale sequencing data. BWA provides accurate and efficient alignment, with the ability to handle various types of reads and reference sequences.