{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T06:26:49Z","timestamp":1771482409325,"version":"3.50.1"},"reference-count":14,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Bisulfite sequencing using next generation sequencers yields genome-wide measurements of DNA methylation at single nucleotide resolution. Traditional aligners are not designed for mapping bisulfite-treated reads, where the unmethylated Cs are converted to Ts. We have developed BS Seeker, an approach that converts the genome to a three-letter alphabet and uses Bowtie to align bisulfite-treated reads to a reference genome. It uses sequence tags to reduce mapping ambiguity. Post-processing of the alignments removes non-unique and low-quality mappings.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>We tested our aligner on synthetic data, a bisulfite-converted <jats:italic>Arabidopsis<\/jats:italic> library, and human libraries generated from two different experimental protocols. We evaluated the performance of our approach and compared it to other bisulfite aligners. The results demonstrate that among the aligners tested, BS Seeker is more versatile and faster. When mapping to the human genome, BS Seeker generates alignments significantly faster than RMAP and BSMAP. Furthermore, BS Seeker is the only alignment tool that can explicitly account for tags which are generated by certain library construction protocols.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>BS Seeker provides fast and accurate mapping of bisulfite-converted reads. It can work with BS reads generated from the two different experimental protocols, and is able to efficiently map reads to large mammalian genomes. The Python program is freely available at <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/pellegrini.mcdb.ucla.edu\/BS_Seeker\/BS_Seeker.html\" ext-link-type=\"uri\">http:\/\/pellegrini.mcdb.ucla.edu\/BS_Seeker\/BS_Seeker.html<\/jats:ext-link>.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2105-11-203","type":"journal-article","created":{"date-parts":[[2010,4,23]],"date-time":"2010-04-23T18:16:05Z","timestamp":1272046565000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":208,"title":["BS Seeker: precise mapping for bisulfite sequencing"],"prefix":"10.1186","volume":"11","author":[{"given":"Pao-Yang","family":"Chen","sequence":"first","affiliation":[]},{"given":"Shawn J","family":"Cokus","sequence":"additional","affiliation":[]},{"given":"Matteo","family":"Pellegrini","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2010,4,23]]},"reference":[{"issue":"5","key":"3660_CR1","doi-asserted-by":"publisher","first-page":"1827","DOI":"10.1073\/pnas.89.5.1827","volume":"89","author":"M Frommer","year":"1992","unstructured":"Frommer M, McDonald LE, Millar DS, Collis CM, Watt F, Grigg GW, Molloy PL, Paul CL: A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands. Proc Natl Acad Sci USA 1992, 89(5):1827\u20131831. 10.1073\/pnas.89.5.1827","journal-title":"Proc Natl Acad Sci USA"},{"issue":"7184","key":"3660_CR2","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1038\/nature06745","volume":"452","author":"SJ Cokus","year":"2008","unstructured":"Cokus SJ, Feng S, Zhang X, Chen Z, Merriman B, Haudenschild CD, Pradhan S, Nelson SF, Pellegrini M, Jacobsen SE: Shotgun bisulphite sequencing of the Arabidopsis genome reveals DNA methylation patterning. Nature 2008, 452(7184):215\u2013219. 10.1038\/nature06745","journal-title":"Nature"},{"issue":"3","key":"3660_CR3","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1016\/j.cell.2008.03.029","volume":"133","author":"R Lister","year":"2008","unstructured":"Lister R, O'Malley RC, Tonti-Filippini J, Gregory BD, Berry CC, Millar AH, Ecker JR: Highly integrated single-base resolution maps of the epigenome in Arabidopsis. Cell 2008, 133(3):523\u2013536. 10.1016\/j.cell.2008.03.029","journal-title":"Cell"},{"issue":"7205","key":"3660_CR4","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1038\/nature07107","volume":"454","author":"A Meissner","year":"2008","unstructured":"Meissner A, Mikkelsen TS, Gu H, Wernig M, Hanna J, Sivachenko A, Zhang X, Bernstein BE, Nusbaum C, Jaffe DB, Gnirke A, Jaenisch R, Lander ES: Genome-scale DNA methylation maps of pluripotent and differentiated cells. Nature 2008, 454(7205):766\u2013770.","journal-title":"Nature"},{"issue":"3","key":"3660_CR5","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/j.ymeth.2009.05.003","volume":"48","author":"ZD Smith","year":"2009","unstructured":"Smith ZD, Gu H, Bock C, Gnirke A, Meissner A: High-throughput bisulfite sequencing in mammalian genomes. Methods 2009, 48(3):226\u2013232. 10.1016\/j.ymeth.2009.05.003","journal-title":"Methods"},{"issue":"7271","key":"3660_CR6","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1038\/nature08514","volume":"462","author":"R Lister","year":"2009","unstructured":"Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, Tonti-Filippini J, Nery JR, Lee L, Ye Z, Ngo QM, Edsall L, Antosiewicz-Bourget J, Stewart R, Ruotti V, Millar AH, Thomson JA, Ren B, Ecker JR: Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 2009, 462(7271):315\u2013322. 10.1038\/nature08514","journal-title":"Nature"},{"issue":"4","key":"3660_CR7","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1101\/gr.229202. Article published online before March 2002","volume":"12","author":"WJ Kent","year":"2002","unstructured":"Kent WJ: BLAT--the BLAST-like alignment tool. Genome Res 2002, 12(4):656\u2013664.","journal-title":"Genome Res"},{"issue":"5","key":"3660_CR8","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1093\/bioinformatics\/btn025","volume":"24","author":"R Li","year":"2008","unstructured":"Li R, Li Y, Kristiansen K, Wang J: SOAP: short oligonucleotide alignment program. Bioinformatics 2008, 24(5):713\u2013714. 10.1093\/bioinformatics\/btn025","journal-title":"Bioinformatics"},{"issue":"3","key":"3660_CR9","doi-asserted-by":"publisher","first-page":"R25","DOI":"10.1186\/gb-2009-10-3-r25","volume":"10","author":"B Langmead","year":"2009","unstructured":"Langmead B, Trapnell C, Pop M, Salzberg SL: Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol 2009, 10(3):R25. 10.1186\/gb-2009-10-3-r25","journal-title":"Genome Biol"},{"key":"3660_CR10","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1186\/1471-2105-10-232","volume":"10","author":"Y Xi","year":"2009","unstructured":"Xi Y, Li W: BSMAP: whole genome bisulfite sequence MAPping program. BMC Bioinformatics 2009, 10: 232. 10.1186\/1471-2105-10-232","journal-title":"BMC Bioinformatics"},{"key":"3660_CR11","volume-title":"Bioinformatics","author":"AD Smith","year":"2009","unstructured":"Smith AD, Chung W, Hodges E, Kendall J, Hannon G, Hicks J, Xuan Z, Zhang MQ: Updates to the RMAP short-read mapping software. Bioinformatics 2009."},{"issue":"11","key":"3660_CR12","doi-asserted-by":"publisher","first-page":"1851","DOI":"10.1101\/gr.078212.108","volume":"18","author":"H Li","year":"2008","unstructured":"Li H, Ruan J, Durbin R: Mapping short DNA sequencing reads and calling variants using mapping quality scores. Genome Res 2008, 18(11):1851\u20131858. 10.1101\/gr.078212.108","journal-title":"Genome Res"},{"issue":"9","key":"3660_CR13","doi-asserted-by":"publisher","first-page":"1593","DOI":"10.1101\/gr.095190.109","volume":"19","author":"E Hodges","year":"2009","unstructured":"Hodges E, Smith AD, Kendall J, Xuan Z, Ravi K, Rooks M, Zhang MQ, Ye K, Bhattacharjee A, Brizuela L, McCombie WR, Wigler M, Hannon GJ, Hicks JB: High definition profiling of mammalian DNA methylation by array capture and single molecule bisulfite sequencing. Genome Res 2009, 19(9):1593\u20131605. 10.1101\/gr.095190.109","journal-title":"Genome Res"},{"issue":"16","key":"3660_CR14","doi-asserted-by":"publisher","first-page":"e105","DOI":"10.1093\/nar\/gkn425","volume":"36","author":"JC Dohm","year":"2008","unstructured":"Dohm JC, Lottaz C, Borodina T, Himmelbauer H: Substantial biases in ultra-short read data sets from high-throughput DNA sequencing. Nucleic Acids Res 2008, 36(16):e105. 10.1093\/nar\/gkn425","journal-title":"Nucleic Acids Res"}],"container-title":["BMC Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2105-11-203.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T05:24:32Z","timestamp":1630473872000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/1471-2105-11-203"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,4,23]]},"references-count":14,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2010,12]]}},"alternative-id":["3660"],"URL":"https:\/\/doi.org\/10.1186\/1471-2105-11-203","relation":{},"ISSN":["1471-2105"],"issn-type":[{"value":"1471-2105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,4,23]]},"assertion":[{"value":"30 December 2009","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 April 2010","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 April 2010","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"203"}}