The article introduces BWA (Burrows-Wheeler Alignment), a new read alignment tool that efficiently aligns short sequencing reads against large reference sequences, such as the human genome. BWA is based on backward search with the Burrows-Wheeler Transform (BWT) and supports both base space and color space reads. It is designed to handle gapped alignment for single-end reads, which is crucial for longer reads where indels are common. Evaluations on simulated and real data show that BWA is approximately 10-20 times faster than MAQ while achieving similar accuracy. BWA outputs alignments in the SAM format, allowing for downstream analyses using SAMtools. The article also discusses the implementation details, memory usage, and performance on real data, highlighting its advantages over other alignment programs like SOAPv2 and Bowtie.The article introduces BWA (Burrows-Wheeler Alignment), a new read alignment tool that efficiently aligns short sequencing reads against large reference sequences, such as the human genome. BWA is based on backward search with the Burrows-Wheeler Transform (BWT) and supports both base space and color space reads. It is designed to handle gapped alignment for single-end reads, which is crucial for longer reads where indels are common. Evaluations on simulated and real data show that BWA is approximately 10-20 times faster than MAQ while achieving similar accuracy. BWA outputs alignments in the SAM format, allowing for downstream analyses using SAMtools. The article also discusses the implementation details, memory usage, and performance on real data, highlighting its advantages over other alignment programs like SOAPv2 and Bowtie.