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Fast and accurate long-read alignment with Burrows-Wheeler transform.
Open accessAbstract
Motivation: Many programs for aligning short sequencing reads to a reference genome have been developed in the last 2 years. Most of them are very efficient for short reads but inefficient or not applicable for reads >200 bp because the algorithms are heavily and specifically tuned for short queries with low sequencing error rate. However, some sequencing platforms already produce longer reads and others are expected to become available soon. For longer reads, hashing-based software such as BLAT and SSAHA2 remain the only choices. Nonetheless, these methods are substantially slower than short-read aligners in terms of aligned bases per unit time. Results: We designed and implemented a new algorithm, Burrows-Wheeler Aligner's Smith-Waterman Alignment (BWA-SW), to align long sequences up to 1 Mb against a large sequence database (e.g. the human genome) with a few gigabytes of memory. The algorithm is as accurate as SSAHA2, more accurate than BLAT, and is several to tens of times faster than both. Availability: http://bio-bwa.sourceforge.net Contact: rd@sanger.ac.uk
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“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 [12]
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“Mapping reads to specific genes is relatively straightforward with the bioinformatics tools available today [10-13], but using these tools to distinguish between reads derived from alternative alleles of the same gene remains challenging [9].”
From Sources of bias in measures of allele-specific expression derived from RNA-seq data aligned to a single reference genome (2013) · cites this paper as [11]
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The Sequence Alignment/Map format and SAMtools
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Self-citationFast and accurate short read alignment with Burrows-Wheeler transform
Li, H., & Durbin, R. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp324 · Cited by 58,607
Self-citationUltrafast and memory-efficient alignment of short DNA sequences to the human genome.
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Influential<tt>BLAT</tt> —The <tt>BLAST</tt> -Like Alignment Tool
Kent, W. J. (2002) · Genome Research · doi:10.1101/gr.229202 · Cited by 8,480 · cited 1×
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SOAP: Short oligonucleotide alignment program
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- Burrows, 1994, A block-sorting lossless data compression algorithm
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Rahimnahal, S., Yousefizadeh, S., & Mohammadi, Y. S. (2026) · PLoS ONE · doi:10.1371/journal.pone.0334662 · Cited by 1
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InfluentialYao, K. T., Yepié, O. F., Fofana, B., Koffi, K. K., Kouakou, K. L., Akaffou, D. S., & Zoro, B. I. A. (2026) · Euphytica · doi:10.1007/s10681-026-03681-1 · Cited by 1
“Using the Burrows-Wheeler Alignment (BWA), BWA MEM algorithm version 0.7.13r1126 (Li and Durbin 2010; Li 2013), the reads were then aligned and mapped against the publicly available high-con-tiguity cashew ( Anacardium occidentale ) reference genome (https:// phyto zome. jgi. doe. gov/ pz/ portal.…”
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“7.17 (Li and Durbin 2010), followed by duplication removal using Picard (https:// sourc eforge. net/ proje cts/ picard/ ).”
InfluentialSelf-citationZhang, Z., Wang, Y., Abid, F. B., Salah, H., Ismail, K. A., Eldos, H. I., Samuel, B. G., Zhou, R., Sundararaju, S., Suleimen, M., et al. (2026) · Microbial Genomics · doi:10.1099/mgen.0.001653 · Cited by 2
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InfluentialLin, L., Neves, A. L. A., Ominski, K., & Guan, L.-L. (2026) · ISME Communications · doi:10.1093/ismeco/ycaf251 · Cited by 1
“The mRNA transcripts from each sample were aligned to the gene catalog using BWA-MEM [22] (v.0.7.17) with a minimum alignment length of 50 bp and a sequence identity threshold of 95%.”
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“Indices for the two MAGs sequences were built using BWA-index, and the reads were mapped to these indices using BWA-MEM [46] (v0.”
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“7.10 (Li & Durbin, 2010).”
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“7.17 (Li and Durbin, 2010; Li, 2013) to remove residual host sequences.”
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“WES reads were aligned to the reference human genome, GRCh37, using BWA-MEM [17].”
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“In the bioinformatic processing, adapter sequences were removed with leeHom (Renaud et al. 2014), and the sequencing reads were mapped to the human reference genome hs37d5 using bwa aln (Li & Durbin 2010), with parameters adjusted for aDNA ( -n 0.01 -o 2 -l 16500).”
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“Rough reads were processed using the fastp tool (Chen, 2023) and mapped against the Nicotiana tabacum reference genome (Nitab v.1.0 Scf Edwards 2017; Edwards et al ., 2017) using B WA (Li & Durbin, 2010).”
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“SRR13005646) and mapped the reads to the final assembly using Burrows– Wheeler Aligner v.0.7.17-r1188 following default parameters (Li and Durbin 2010), and the read mapping statistics were generated using SAMtools v1.”
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“We used Burrows-Wheeler Aligner (BWA) mem version 0.7.17 (Li and Durbin 2010) to map the reads to the reference genomes.”
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“Sequencing reads were aligned against the GRCh38/hg38 build using the Borrows-Wheeler Aligner version 2.2.1 [23].”
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Luck, J. N., D’Mello, A., Chembilikandy, V., Lane, J. R., Kruckow, K. L., Martínez, E., Rodriguez, E., Mohasin, M., Berg, I., Porter, K. D., et al. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.116574 · Cited by 1
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Integrated genomic analysis and CRISPRi implicates EGFR in Alzheimer’s disease risk
Leung, Y. Y., Kuksa, P. P., Carter, L., Cifello, J., Greenfest‐Allen, E., Valladares, O., Boateng, L., Laub, S., Tulina, N. M., Moura, S., et al. (2025) · npj Dementia · doi:10.1038/s44400-025-00049-5 · Cited by 4
“Sequencing data were processed using BWA 76 to map each read end separately to the GRCh38 reference genomes.”
Li, X.-C., San, L., Wang, G.-X., Li, B.-B., He, Z.-W., Liu, Y.-F., Ren, Y.-Q., Hou, J.-L., & Zhang, X.-Y. (2025) · Aquaculture · doi:10.1016/j.aquaculture.2025.743582 · Cited by 1
Xiong, Y.-L., Yu, Q., Xiong, Y., You, M.-H., He, L., Wu, G.-C., Peng, J., Yan, L.-J., Deng, D., Ma, X., et al. (2025) · Journal of genetics and genomics = Yi chuan xue bao · doi:10.1016/j.jgg.2025.12.011 · Cited by 1
Social Stratification Without Genetic Differentiation at the Xisima Site in the Late Shang Dynasty
Tang, J., Wang, R., Wei, Q., He, H., Deng, C., Tao, L., Mao, X., Ma, H., Wang, X., Zou, X., et al. (2025) · Molecular Biology and Evolution · doi:10.1093/molbev/msaf316 · Cited by 1
“…were aligned against the human reference genome hs37d5 (GRCh37 with decoy sequences) using the aln and samse modules in the Burrows-Wheeler Aligner (BWA) program (version 0.7.17-r1188) (Li and Durbin 2010), with parameters “-l 1024” (seeding disabled) and “-n 0.01” (additional mismatches allowed).”
InfluentialSpeciation Genomics in the Tiger Whiptail Lizards (Aspidoscelis tigris Complex)
Barley, A. J., Ho, D. V., Baumann, P., Wang, I. J., Shaffer, H., Fisher, R. N., Gray, L. N., Krabbenhoft, T. J., Espinoza, R. E., Escalona, M., et al. (2025) · Genome Biology and Evolution · doi:10.1093/gbe/evaf218 · Cited by 1
“…whole-genome sequence data for one individual from each lineage (i.e., DNAseq data for A. t. aethiops and A. marmoratus and Omni-C data for A. t. stejnegeri ) to the A. tigris reference genome using the BWA-MEM algorithm (Li and Durbin 2010), after trimming the sequence data with Trimmomatic v0.”
Fu, J.-H., & Hong, M.-S. (2025) · Mitochondrial DNA Part B: Resources · doi:10.1080/23802359.2025.2535653 · Cited by 1
“7.18) (Li and Durbin 2010) for alignment and SAMtools (v1.”
InfluentialΚοσμαρά, Δ., Papanikolaou, S., Stathopoulou, C., Papamatheakis, D.-A., Vatsellas, G., Cimmarrusti, A., Banos, A., Sidiropoulos, P. I., Lavigne, M. D., Verginis, P., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-65309-7 · Cited by 1
“FilteredreadswerethenmappedagainsttheUCSChg19human reference genome using bwa-mem aligner 108 with default parameters.”
Campbell, M. A., Perry, S. C., Yearwood, K. N., Auringer, G., Buckmaster, N., & Finger, A. (2025) · ZooKeys · doi:10.3897/zookeys.1261.151636 · Cited by 1
“1) with the Burrows-Wheeler aligner and the MEM algorithm (bwa mem) (Li and Durbin 2010).”
Amr, K. S., El-Bassyouni, H. T., Rabie, E., Fadel, F. I., Teama, N. M., Selim, A., Hamed, K., Helmy, R., El-Salam, M. A., & Ahmed, H. A. (2025) · Molecular Biology Reports · doi:10.1007/s11033-025-11169-9 · Cited by 1
Prevalence of deleterious variants in cardiomyopathy genes in early-onset atrial fibrillation
Lundegaard, P., Vad, O., Vilaseca, Q., Beyer, A., Paludan-Müller, C., Andreasen, L., & Svendsen, J. (2025) · Research Square · doi:10.21203/rs.3.rs-7971912/v1 · Cited by 1
“Sequenced reads were trimmed and �ltered for low-quality reads, aligned to the Human Reference Genome (build GRCh37/bg19) using the Burrows-Wheeler Aligner software(10), and postprocessed according to the Genome Analysis Toolkit best practice guidelines(11).”
Gupta, S., Srivastava, P., Daniel, R., Bhardwaj, C., Kaur, P., Bawa, P., Kumari, A., Bhadoriya, R. P. S., Peters, M., Kaur, A., et al. (2025) · Frontiers in Genetics · doi:10.3389/fgene.2025.1677143 · Cited by 1
“Sequence reads were aligned to the human genome assembly GRCH38 using the Burrows – Wheeler Aligner (BWA) with the MEM algorithm (Li and Durbin, 2010).”
SeraSeq reference materials support non-invasive cfDNA screening methods.
Giroux, S., Daryabari, S. S., Caron, A., & Rousseau, F. (2025) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2025.111046 · Cited by 1
Junkiert-Czarnecka, A., Maciak, K., Kacprzak, M. M., Łobodzińska, A., Sobczyńska-Tomaszewska, A., Jurkiewicz, A., Góra, M., Burzyńska, B., Pilarska-Deltow, M., & Haus, O. (2025) · Frontiers in Genetics · doi:10.3389/fgene.2025.1689587 · Cited by 1
“2.1 (Li and Durbin, 2010).”
InfluentialEgas, R. A., Bale, N., Koenen, M., Villanueva, L., Sousa, D. Z., Welte, C., & Sánchez-Andrea, I. (2025) · bioRxiv · doi:10.1101/2025.11.06.686915 · Cited by 1
Accelerating Multiple Sequence Alignment Via Maximal Exact Match Identification
Wehning, T., & Alachiotis, N. (2025) · International Conferences on Biological Information and Biomedical Engineering · doi:10.1109/bibe66822.2025.00066 · Cited by 1
“In genomics, MSA is essential for comparing genetic sequences to identify mutations that may be linked to diseases or traits [2].”
F2 bulk segregant analysis reveals salt-tolerant QTLs related to the ubiquitination process
Habila, S., Khunpolwattana, N., Buabooch, T., Henry, I. M., Comai, L., Pongpanich, M., Plaimas, K., Suriya-arunroj, D., Siangliw, M., Kasettranun, W., et al. (2025) · Scientific Reports · doi:10.1038/s41598-025-22480-7 · Cited by 1
“After excluding the reads with low-quality bases (quality score less than 30), the clean reads were mapped against the Nipponbare reference genome (release 7) 43 using Burrows–Wheeler Aligner (BWA version 0.7.15) software with the BWA–MEM algorithm 101 .”
InfluentialKeene-Snickers, A. H., Brehm, A. L., Dunham, T. J., Gelpi, T. A., & Stenglein, M. (2025) · Virus Evolution · doi:10.1093/ve/veaf089 · Cited by 1
“Draft galbut virus sequences were manually validated by remapping of trimmed r eads using bwa mem aligner version 0.7.17 (Li and Durbin 2010).”
InfluentialPhylogeny and Climate Change–Driven Distribution Dynamics of Keteleeria
Yuan, Y., Wang, J.-H., Guo, Y., Wang, Z., Liu, S., & Jia, Z.-R. (2025) · Diversity and Distributions: A journal of biological invasions and biodiversity · doi:10.1111/ddi.70116 · Cited by 1
“7.8-r455 program (Li and Durbin 2010; Li and Durbin 2009).”
InfluentialParsad, R., Ahlawat, S., Chhabra, P., Sharma, U., Arora, R., Sharma, R., Gera, R., & Bagiyal, M. (2025) · Small Ruminant Research · doi:10.1016/j.smallrumres.2025.107600 · Cited by 1
Lin, F.-W., Zhao, M.-Q., Wu, Q., Wu, W., Wu, X.-Y., Ma, Y., Yin, J.-N. C., Yang, M., & Gao, M. (2025) · Genes, Chromosomes and Cancer · doi:10.1002/gcc.70088 · Cited by 1
“The filtered paired-end reads were mapped to the human genome reference (GRCh37, hg19) using the Burrows-Wheeler Aligner [28] and realigned around indels using GATK3 [29].”
Alam, M. J., Kodama, N., Ikeda, K., Muraki, K., Higuchi, Y., Fujita, M., Kamimura, N., Masai, E., Kurihara, H., & Sonoki, T. (2025) · Journal of Bioscience and Bioengineering · doi:10.1016/j.jbiosc.2025.11.001 · Cited by 1
Ekinci, R. M. K., Ceylaner, S., Devrez, F. D., & Koç, A. S. (2025) · Expert Review of Clinical Immunology · doi:10.1080/1744666x.2025.2582490 · Cited by 1
“Alignment to (GRCh38) was done using BWA-MEM 0.7.17 [16].”
InfluentialWan, W., Wu, Z.-N., Tian, C.-Y., Yang, Y.-T., Li, Z.-Y., Gong, W.-L., Liu, L.-M., & Li, Y. (2025) · Planta · doi:10.1007/s00425-025-04860-5 · Cited by 1
“7.15) (Li and Durbin 2010), followed by SNP naming using SAMtools (v1.”
InfluentialWade, C., Burmeister, L., Skelly, B. J., Mclaughlin, B., Pettitt, L., Atwater, D., Tallmadge, R., Lejeune, M., Lindblad-Toh, K., & Mellersh, C. (2025) · Animal Genetics · doi:10.1111/age.70056 · Cited by 1
Zheng, Y.-C., Tu, Y., Badano, D., & Liu, X.-Y. (2025) · Arthropod Systematics & Phylogeny · doi:10.3897/asp.83.e145082 · Cited by 1
“Raw reads were trimmed of adapters using BWA (Burrows-Wheeler Aligner) software (Li and Durbin 2010).”
Wang, Z., Cai, C.-P., Zhu, G.-Z., Zhou, X., Xiao, S., Tan, Y., Zhou, Y., Shang, X.-G., & Guo, W.-Z. (2025) · Theoretical and Applied Genetics · doi:10.1007/s00122-025-05061-0 · Cited by 1
“TM-1 (Hu et al. 2019) using BWA software (Li and Durbin 2010), and the GATK and SAMtools software were applied to identify single nucleotide polymorphisms (SNPs) and insertion/deletions (InDels) (Li et al. 2009; McKenna et al. 2010).”
You, T., Wang, L., Gao, Y., Tian, Y., Yang, Q., & Yang, X.-Y. (2025) · Ethnobiology and Conservation · doi:10.15451/ec2025-10-14-34-1-13 · Cited by 1
Contrasting roles of KMT2C and KMT2D in breast cancer
Tinsley, E. A., Bredin, P., Toomey, S., Hennessy, B. T., & Furney, S. J. (2025) · Scientific Reports · doi:10.1038/s41598-025-19027-1
Spinella, J., Chagraoui, J., Moison, C., Boivin, I., Carpentier, G. R., Mayotte, N., Béliveau, F., Lavallée, V.-P., Hébert, J., & Sauvageau, G. (2025) · bioRxiv · doi:10.1101/2025.10.01.679539 · Cited by 1
Nanopore Sequencing Reveals Novel Alternative Splice Variants of EZH2 in Pediatric Medulloblastoma
Ramírez-Chiquito, J. C., Rosete-Ambriz, S. A., Olguín-García, A. C., Eguía-Aguilar, M. D. P., Niembro-Zúñiga, A., Marhx-Bracho, A., Perezpeña-Diazconti, M., & Juárez-Méndez, S. (2025) · Biomedicines · doi:10.3390/biomedicines13102461 · Cited by 1
“The FASTQ files containing the raw sequencing data were aligned against the human reference genome (GRCh38) via the minimap2 method (version 2.28) in Galaxy (version 2.2.1+galaxy1) online software (https://usegalaxy.org/, accessed on 24 September 2025) [31,32].”
InfluentialChoi, N., Kang, I.-J., & Nam, K. (2025) · Evolutionary Applications · doi:10.1111/eva.70171 · Cited by 1
“The filtered reads were mapped to the N. lugens reference genome (Ma et al. 2021) using BWA-MEM v 0.7.17 (Li and Durbin 2010) with default parameters.”
InfluentialQuan, M.-Y., Zhou, J.-X., Khan, M., Zhang, R., Jiang, Y., Wang, D., Zhao, T., Jin, Z.-Y., Du, Q., & Zhang, D.-Q. (2025) · Industrial crops and products (Print) · doi:10.1016/j.indcrop.2025.121476 · Cited by 1
Jochim, E. E., Starrett, J., Briggs, H., & Bond, J. E. (2025) · Ecology and Evolution · doi:10.1002/ece3.72346 · Cited by 1
Development and performance of a SNP array for black tiger shrimp and a GWAS for sex determination
Kijas, J., Carvalheiro, R., Menzies, M., McWilliam, S., Reverter, A., Alexandre, P., Coman, G., Ma, T., Dinh, L., Nguyen, C. C., et al. (2025) · Aquaculture · doi:10.1016/j.aquaculture.2025.743356 · Cited by 1
Jiang, K., Dai, Z.-H., Chen, J., Gao, Z., Tong, H.-Y., Liu, H.-R., Huang, G.-N., Liu, F., Ma, Y., Pan, E., et al. (2025) · Diagnostic Pathology · doi:10.1186/s13000-025-01697-0 · Cited by 1
“The filtered paired-end reads were then aligned to the human genome reference (GRCh37, hg19) using the Burrows-Wheeler Aligner [12], followed by realignment around indels performed with GATK3 [13].”
Meng, K., Qin, Y., Qu, J., Lee, S.-O.-Y., Lu, L.-Y., Zou, P., & Huang, G.-D. (2025) · Mitochondrial DNA Part B: Resources · doi:10.1080/23802359.2025.2550612 · Cited by 1
“7.17 (Li and Durbin 2010) with default parameters.”
InfluentialProposal of Bacillus altaicus sp. nov. Isolated from Soil in the Altai Region, Russia
Shikov, A. E., Romanenko, M. N., Shmatov, F. M., Belousov, M. V., Solovchenko, A. E., Chivkunova, O. B., Savelev, G. K., Kuznetsova, I. G., Karlov, D. S., Nizhnikov, A. A., et al. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26199517 · Cited by 2
“0.1 (Oxford Nanopore Technologies Ltd., UK) and short reads-based polishing with BWA 0.7.18-r1243-dirty [100], SAMtools v1.”
InfluentialWang, Y., Wang, J., Ding, H., Lian-xi, Y., Zhao, H., & Huang, D. (2025) · Frontiers in Veterinary Science · doi:10.3389/fvets.2025.1612883 · Cited by 1
Zhang, J., Zhang, F., Qu, Y., Suo, M., Song, G., Chen, Y., & Cai, D. (2025) · Archaeological and Anthropological Sciences · doi:10.1007/s12520-025-02325-0 · Cited by 2
“7.17 with the arguments -n 0.01 and -l 16500 (Li and Durbin 2010).”
InfluentialGuo, K., Ahrens, C., Chen, S. H., Sandhu, K., Rossetto, M., Jones, A. W., Tan, C., Borevitz, J. O., Edwards, R., & Bragg, J. G. (2025) · bioRxiv · doi:10.1111/mec.70413 · Cited by 1
“7.17-r1188, Li and Durbin 2010).”
InfluentialDai, J., Zhang, Y., Gao, Y., Li, H., Du, S., Hong, H., You, D., Li, Z., Zhang, R., Zhao, Y., et al. (2025) · Genomics Proteomics & Bioinformatics · doi:10.1093/gpbjnl/qzaf084 · Cited by 5
“Sequence reads were mapped to the human reference genome GRCh38 using Burrows–Wheeler Alignment (BWA), an efficient read alignment tool based on Burrows–Wheeler Transform [49].”
Self-citationHan, Z., Zheng, W.-N., Li, Y., Ou, Q., Zhao, H., Zhao, H., Xu, J., Chai, S., Yang, X.-Y., Zhang, Z.-H., et al. (2025) · Theoretical and Applied Genetics · doi:10.1007/s00122-025-05038-z · Cited by 1
“Paired-end clean reads were aligned to the Cme13C reference genome using BWA-MEM version 0.7.17-r1188 (Li and Durbin 2010).”
InfluentialA comparison of two universal angiosperm bait sets and the phylogenomics of AlismatalesPreprint
Biffin, E., Waycott, M., Hammer, T., & van Dijk, K.-J. (2025) · bioRxiv · doi:10.1101/2025.09.15.676180 · Cited by 1
“Read depth estimates were generated using the SECAPR reference_assembly function (Andermann et al. 2018), which uses the BWA mapper (Li and Durbin, 2010) for reference-based mapping and Picard (broadinstitute.github.io/picard/) for removing duplicate reads.”
Metadata
- Authors
- Li, H., & Durbin, R.
- Affiliations
- Wellcome Sanger Institute (GB)
- Corresponding author
- Durbin, Richard
- Venue
- Bioinformatics
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-01-15
- Volume
- 26
- Issue
- 5
- Pages
- 589-595
- ISSN
- 1367-4803 (ISSN-L)
- 1367-4811
- PMC
- PMC2828108
- OpenAlex
- W4247053599
- Cited by
- 12,063
- References
- 24
- Citations by year
- 2026: 639 · 2025: 972 · 2024: 1129 · 2023: 1067 · 2022: 1203 · 2021: 1245 · 2020: 1176 · 2019: 941 · 2018: 826 · 2017: 747 · 2016: 574 · 2015: 498 · 2014: 419 · 2013: 301 · 2012: 203
- FWCI
- 80.44
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Bioinformatics (publishedVersion, cc-by-nc)
- Funders
- Wellcome Trust (077192/Z/05/Z)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Physical Sciences › Mathematics › Theoretical Computer Science › Algorithms and Data Compression
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fractal and DNA sequence analysis
- Keywords
- long-read alignment, Burrows-Wheeler transform, Smith-Waterman alignment, sequence alignment, reference genome, blat, alignment speed, alignment accuracy, human genome
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