Fast gapped-read alignment with Bowtie 2
Open accessAbstract
As the rate of sequencing increases, greater throughput is demanded from read aligners. The full-text minute index is often used to make alignment very fast and memory-efficient, but the approach is ill-suited to finding longer, gapped alignments. Bowtie 2 combines the strengths of the full-text minute index with the flexibility and speed of hardware-accelerated dynamic programming algorithms to achieve a combination of high speed, sensitivity and accuracy.
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Bowtie2, BWA, HISAT2, STAR or any tool wrapping one of these aligners are confirmed to work for alignment to N-masked genomes.
“Software confirmed to be working for this approach include (but are not limited to) Bowtie2 11, BWA 12, HISAT2 13, STAR 14 or any tool wrapping one of these aligners.”
From SNPsplit: Allele-specific splitting of alignments between genomes with known SNP genotypes (2016) · cites this paper as [11]
The paper’s Abstract (page not provided) identifies Bowtie 2 as a read aligner and reports its use with a human reference genome, supporting its identification in the list. It does not say that Bowtie 2 was tested or confirmed to work with N-masked genomes; searches for masked bases and ambiguous reference characters found no such passage. The other aligners have separate citations in the citing sentence and are not assessed here. (LLM, conf=0.84)
Experimental — accuracy not yet measuredRaw reads were processed and mapped to the Mus musculus reference genome (Ensembl release 99) using bowtie with an average mapping rate of 87.1%.
“Raw reads were processed and mapped to the Mus musculus reference genome (Ensembl release 99) using bowtie with an average mapping rate of 87.1% [96]”
From Rapid changes in plasma corticosterone and medial amygdala transcriptome profiles during social status change reveal molecular pathways associated with a major life history transition in mouse dominance hierarchies (2025) · cites this paper as [96]
The paper’s main text describes Bowtie 2 as a read aligner, so it supports citing an alignment method. It explicitly compares Bowtie 2 with Bowtie as a separate tool, however, and its experiments use a human reference genome; it does not report the citing study’s mouse reference or 87.1% mapping rate. (LLM, conf=0.83)
Experimental — accuracy not yet measuredPoullet et al. find that end-to-end mode is optimal for Bowtie2 in an aDNA context.
“and Poullet et al. find that –end-to-end mode is optimal for Bowtie2 [12] in an aDNA context [13].”
From <tt>SAFARI</tt> : pangenome alignment of ancient DNA using purine/pyrimidine encodings (2025) · cites this paper as [12]
Using Bowtie2 in end-to-end mode without allowing gaps guarantees that all merged reads that can be mapped to the reference genome are correctly merged.
“This guarantees that all merged reads that can be mapped to the reference genome are correctly merged.”
From PEAR: a fast and accurate Illumina Paired-End reAd mergeR (2014) · cites this paper as Langmead and Salzberg, 2012
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- Authors
- Langmead, B., & Salzberg, S. L.
- Affiliations
- University of Maryland, College Park (US)
- Johns Hopkins University (US)
- Corresponding author
- Langmead, Ben
- Venue
- Nature Methods
- Published
- 2012-03-04
- Volume
- 9
- Issue
- 4
- Pages
- 357-359
- ISSN
- 1548-7091 (ISSN-L)
- 1548-7105
- PMC
- PMC3322381
- OpenAlex
- W2170551349
- Cited by
- 56,400
- References
- 14
- Citations by year
- 2026: 4721 · 2025: 6064 · 2024: 6626 · 2023: 5993 · 2022: 6184 · 2021: 6377 · 2020: 5187 · 2019: 4093 · 2018: 3406 · 2017: 2791 · 2016: 2000 · 2015: 1529 · 2014: 955 · 2013: 385 · 2012: 56
- FWCI
- 376.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Methods (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Human Genome Research Institute (R01HG006102, R01HG006677)
- National Institute of General Medical Sciences (R01GM083873)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Physical Sciences › Computer Science › Artificial Intelligence › Algorithms and Data Compression
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fractal and DNA sequence analysis
- Keywords
- memory-efficient alignment
- MeSH terms
- Algorithms, Humans, Genome, Human, Sequence Alignment, Sequence Analysis, DNA, Computational Biology, Databases, Genetic
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