{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T04:11:12Z","timestamp":1772165472645,"version":"3.50.1"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T00:00:00Z","timestamp":1753056000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T00:00:00Z","timestamp":1753056000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"DOI":"10.1186\/s12859-025-06182-5","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T14:25:03Z","timestamp":1753107903000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Aryana-bs: context-aware alignment of bisulfite-sequencing reads"],"prefix":"10.1186","volume":"26","author":[{"given":"Hassan","family":"Nikaein","sequence":"first","affiliation":[]},{"given":"Ali","family":"Sharifi-Zarchi","sequence":"additional","affiliation":[]},{"given":"Afsoon","family":"Afzal","sequence":"additional","affiliation":[]},{"given":"Saeedeh","family":"Ezzati","sequence":"additional","affiliation":[]},{"given":"Farzane","family":"Rasti","sequence":"additional","affiliation":[]},{"given":"Hamidreza","family":"Chitsaz","sequence":"additional","affiliation":[]},{"given":"Govindarajan","family":"Kunde-Ramamoorthy","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2025,7,21]]},"reference":[{"issue":"8","key":"6182_CR1","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1038\/ng1598","volume":"37","author":"M Weber","year":"2005","unstructured":"Weber M, Davies JJ, Wittig D, Oakeley EJ, Haase M, Lam WL, Schuebeler D. Chromosome-wide and promoter-specific analyses identify sites of differential dna methylation in normal and transformed human cells. Nat Genet. 2005;37(8):853\u201362.","journal-title":"Nat Genet"},{"key":"6182_CR2","doi-asserted-by":"crossref","unstructured":"Varriale A. Dna methylation, epigenetics, and evolution in vertebrates: facts and challenges. Int J Evolut Biol 2014 (2014)","DOI":"10.1155\/2014\/475981"},{"key":"6182_CR3","doi-asserted-by":"crossref","unstructured":"Hayatsu H. Discovery of bisulfite-mediated cytosine conversion to uracil, the key reaction for dna methylation analysis\u2014a personal account. Proceedings of the Japan Academy, Series B. 2008;84(8):321\u201330.","DOI":"10.2183\/pjab.84.321"},{"issue":"1","key":"6182_CR4","doi-asserted-by":"publisher","first-page":"3","DOI":"10.3390\/biology5010003","volume":"5","author":"S Kurdyukov","year":"2016","unstructured":"Kurdyukov S, Bullock M. Dna methylation analysis: choosing the right method. Biology. 2016;5(1):3.","journal-title":"Biology"},{"issue":"18","key":"6182_CR5","doi-asserted-by":"publisher","first-page":"5868","DOI":"10.1093\/nar\/gki901","volume":"33","author":"A Meissner","year":"2005","unstructured":"Meissner A, Gnirke A, Bell GW, Ramsahoye B, Lander ES, Jaenisch R. Reduced representation bisulfite sequencing for comparative high-resolution dna methylation analysis. Nucleic Acids Res. 2005;33(18):5868\u201377.","journal-title":"Nucleic Acids Res"},{"key":"6182_CR6","doi-asserted-by":"crossref","unstructured":"Li H, Durbin R. Fast and accurate short read alignment with burrows\u2013wheeler transform. bioinformatics, (2009);25(14), 1754\u20131760","DOI":"10.1093\/bioinformatics\/btp324"},{"issue":"4","key":"6182_CR7","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nmeth.1923","volume":"9","author":"B Langmead","year":"2012","unstructured":"Langmead B, Salzberg SL. Fast gapped-read alignment with bowtie 2. Nat Methods. 2012;9(4):357\u20139.","journal-title":"Nat Methods"},{"issue":"6","key":"6182_CR8","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1089\/cmb.2012.0022","volume":"19","author":"S Schbath","year":"2012","unstructured":"Schbath S, Martin V, Zytnicki M, Fayolle J, Loux V, Gibrat J-F. Mapping reads on a genomic sequence: an algorithmic overview and a practical comparative analysis. J Comput Biol. 2012;19(6):796\u2013813.","journal-title":"J Comput Biol"},{"key":"6182_CR9","doi-asserted-by":"crossref","unstructured":"Feng S, Rubbi L, Jacobsen SE, Pellegrini M. Determining dna methylation profiles using sequencing. In: High-Throughput Next Generation Sequencing. Springer, (2011), pp. 223\u2013238","DOI":"10.1007\/978-1-61779-089-8_16"},{"issue":"11","key":"6182_CR10","doi-asserted-by":"publisher","first-page":"1571","DOI":"10.1093\/bioinformatics\/btr167","volume":"27","author":"F Krueger","year":"2011","unstructured":"Krueger F, Andrews SR. Bismark: a flexible aligner and methylation caller for bisulfite-seq applications. Bioinformatics. 2011;27(11):1571\u20132.","journal-title":"Bioinformatics"},{"issue":"10","key":"6182_CR11","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1038\/nrg3273","volume":"13","author":"C Bock","year":"2012","unstructured":"Bock C. Analysing and interpreting dna methylation data. Nat Rev Genet. 2012;13(10):705\u201319.","journal-title":"Nat Rev Genet"},{"key":"6182_CR12","doi-asserted-by":"publisher","first-page":"4704","DOI":"10.1016\/j.csbj.2022.08.051","volume":"20","author":"W Gong","year":"2022","unstructured":"Gong W, Pan X, Xu D, Ji G, Wang Y, Tian Y, Cai J, Li J, Zhang Z, Yuan X. Benchmarking dna methylation analysis of 14 alignment algorithms for whole genome bisulfite sequencing in mammals. Comput Struct Biotechnol J. 2022;20:4704\u201316.","journal-title":"Comput Struct Biotechnol J"},{"issue":"1","key":"6182_CR13","doi-asserted-by":"publisher","first-page":"1","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 Bioinform. 2009;10(1):1\u20139.","journal-title":"BMC Bioinform"},{"key":"6182_CR14","doi-asserted-by":"crossref","unstructured":"Gholami M, Arbabi A, Sharifi-Zarchi A, Chitsaz H, Sadeghi M. Aryana: Aligning reads by yet another approach. In: BMC Bioinformatics, (2014);vol. 15, pp. 1\u201310. BioMed Central","DOI":"10.1186\/1471-2105-15-S9-S12"},{"key":"6182_CR15","unstructured":"Pedersen BS, Eyring K, De S, Yang IV, Schwartz DA. Fast and accurate alignment of long bisulfite-seq reads. arXiv (2014). https:\/\/arxiv.org\/abs\/1401.1129"},{"issue":"5","key":"6182_CR16","doi-asserted-by":"publisher","first-page":"033","DOI":"10.1093\/gigascience\/giab033","volume":"10","author":"C Farrell","year":"2021","unstructured":"Farrell C, Thompson M, Tosevska A, Oyetunde A, Pellegrini M. Bisulfite bolt: A bisulfite sequencing analysis platform. Gigascience. 2021;10(5):033.","journal-title":"Gigascience"},{"issue":"4","key":"6182_CR17","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1093\/nargab\/lqab115","volume":"3","author":"G Sena Brandine","year":"2021","unstructured":"Sena Brandine G, Smith AD. Fast and memory-efficient mapping of short bisulfite sequencing reads using a two-letter alphabet. NAR Genom Bioinform. 2021;3(4):115.","journal-title":"NAR Genom Bioinform"},{"key":"6182_CR18","unstructured":"Sherman, A simple Bisulfite FastQ Read Simulator (BiQRS). https:\/\/github.com\/FelixKrueger\/Sherman"},{"issue":"6","key":"6182_CR19","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1093\/nar\/gkt1325","volume":"42","author":"G Kunde-Ramamoorthy","year":"2014","unstructured":"Kunde-Ramamoorthy G, Coarfa C, Laritsky E, Kessler NJ, Harris RA, Xu M, Chen R, Shen L, Milosavljevic A, Waterland RA. Comparison and quantitative verification of mapping algorithms for whole-genome bisulfite sequencing. Nucleic Acids Res. 2014;42(6):43\u201343.","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"6182_CR20","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1038\/npp.2012.112","volume":"38","author":"LD Moore","year":"2013","unstructured":"Moore LD, Le T, Fan G. Dna methylation and its basic function. Neuropsychopharmacology. 2013;38(1):23\u201338.","journal-title":"Neuropsychopharmacology"},{"issue":"3","key":"6182_CR21","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1101\/gr.147942.112","volume":"23","author":"KE Varley","year":"2013","unstructured":"Varley KE, Gertz J, Bowling KM, Parker SL, Reddy TE, Pauli-Behn F, Cross MK, Williams BA, Stamatoyannopoulos JA, Crawford GE. Dynamic dna methylation across diverse human cell lines and tissues. Genome Res. 2013;23(3):555\u201367.","journal-title":"Genome Res"},{"issue":"6","key":"6182_CR22","doi-asserted-by":"publisher","first-page":"823","DOI":"10.4161\/epi.28741","volume":"9","author":"V Patil","year":"2014","unstructured":"Patil V, Ward RL, Hesson LB. The evidence for functional non-cpg methylation in mammalian cells. Epigenetics. 2014;9(6):823\u20138.","journal-title":"Epigenetics"},{"issue":"6","key":"6182_CR23","doi-asserted-by":"publisher","first-page":"148","DOI":"10.3390\/genes8060148","volume":"8","author":"HS Jang","year":"2017","unstructured":"Jang HS, Shin WJ, Lee JE, Do JT. Cpg and non-cpg methylation in epigenetic gene regulation and brain function. Genes. 2017;8(6):148.","journal-title":"Genes"},{"issue":"5","key":"6182_CR24","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1093\/bfgp\/elab035","volume":"20","author":"D Ramasamy","year":"2021","unstructured":"Ramasamy D, Rao Deva Magendhra AK, Rajkumar T, Mani S. Non-cpg methylation-a key epigenetic modification in cancer. Brief Funct Genom. 2021;20(5):304\u201311.","journal-title":"Brief Funct Genom"},{"issue":"6","key":"6182_CR25","doi-asserted-by":"publisher","first-page":"1002750","DOI":"10.1371\/journal.pgen.1002750","volume":"8","author":"J Arand","year":"2012","unstructured":"Arand J, Spieler D, Karius T, Branco MR, Meilinger D, Meissner A, Jenuwein T, Xu G, Leonhardt H, Wolf V. In vivo control of cpg and non-cpg dna methylation by dna methyltransferases. PLoS Genet. 2012;8(6):1002750.","journal-title":"PLoS Genet"},{"key":"6182_CR26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/gm346","volume":"4","author":"D Balasubramanian","year":"2012","unstructured":"Balasubramanian D, Akhtar-Zaidi B, Song L, Bartels CF, Veigl M, Beard L, Myeroff L, Guda K, Lutterbaugh J, Willis J. H3k4me3 inversely correlates with dna methylation at a large class of non-cpg-island-containing start sites. Genome Med. 2012;4:1\u201311.","journal-title":"Genome Med"},{"issue":"19","key":"6182_CR27","first-page":"114","volume":"46","author":"M Catoni","year":"2018","unstructured":"Catoni M, Tsang JM, Greco AP, Zabet NR. Dmrcaller: a versatile r\/bioconductor package for detection and visualization of differentially methylated regions in cpg and non-cpg contexts. Nucleic Acids Res. 2018;46(19):114\u2013114.","journal-title":"Nucleic Acids Res"},{"issue":"5","key":"6182_CR28","doi-asserted-by":"publisher","first-page":"553","DOI":"10.2217\/epi.13.43","volume":"5","author":"M Ehrlich","year":"2013","unstructured":"Ehrlich M, Lacey M. Dna methylation and differentiation: silencing, upregulation and modulation of gene expression. Epigenomics. 2013;5(5):553\u201368.","journal-title":"Epigenomics"},{"issue":"10","key":"6182_CR29","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1038\/s41580-019-0159-6","volume":"20","author":"MV Greenberg","year":"2019","unstructured":"Greenberg MV, Bourc\u2019his D. The diverse roles of dna methylation in mammalian development and disease. Nat Rev Molecular Cell Biol. 2019;20(10):590\u2013607.","journal-title":"Nat Rev Molecular Cell Biol"},{"issue":"1","key":"6182_CR30","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1038\/hdy.2010.44","volume":"105","author":"M Rountree","year":"2010","unstructured":"Rountree M, Selker E. Dna methylation and the formation of heterochromatin in neurospora crassa. Heredity. 2010;105(1):38\u201344.","journal-title":"Heredity"},{"issue":"3","key":"6182_CR31","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.1104\/pp.18.00352","volume":"177","author":"F Tan","year":"2018","unstructured":"Tan F, Lu Y, Jiang W, Wu T, Zhang R, Zhao Y, Zhou D-X. Ddm1 represses noncoding rna expression and rna-directed dna methylation in heterochromatin. Plant Physiol. 2018;177(3):1187\u201397.","journal-title":"Plant Physiol"},{"issue":"1","key":"6182_CR32","doi-asserted-by":"publisher","first-page":"2490","DOI":"10.1038\/s41467-021-22665-4","volume":"12","author":"W Ren","year":"2021","unstructured":"Ren W, Fan H, Grimm SA, Kim JJ, Li L, Guo Y, Petell CJ, Tan X-F, Zhang Z-M, Coan JP. Dnmt1 reads heterochromatic h4k20me3 to reinforce line-1 dna methylation. Nat Commun. 2021;12(1):2490.","journal-title":"Nat Commun"},{"issue":"3","key":"6182_CR33","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1038\/s41592-022-01412-7","volume":"19","author":"T Zhu","year":"2022","unstructured":"Zhu T, Liu J, Beck S, Pan S, Capper D, Lechner M, Thirlwell C, Breeze CE, Teschendorff AE. A pan-tissue dna methylation atlas enables in silico decomposition of human tissue methylomes at cell-type resolution. Nat Methods. 2022;19(3):296\u2013306.","journal-title":"Nat Methods"},{"issue":"8","key":"6182_CR34","doi-asserted-by":"publisher","first-page":"1407","DOI":"10.1101\/gr.132878.111","volume":"22","author":"A Hogart","year":"2012","unstructured":"Hogart A, Lichtenberg J, Ajay SS, Anderson S, Margulies EH, Bodine DM, Center NIS. Genome-wide dna methylation profiles in hematopoietic stem and progenitor cells reveal overrepresentation of ets transcription factor binding sites. Genome Res. 2012;22(8):1407\u201318.","journal-title":"Genome Res"},{"issue":"3","key":"6182_CR35","doi-asserted-by":"publisher","first-page":"734","DOI":"10.3390\/jcm9030734","volume":"9","author":"Y Shin","year":"2020","unstructured":"Shin Y, Kim M, Won J, Kim J, Oh SB, Lee J-H, Park K. Epigenetic modification of cftr in head and neck cancer. J Clin Med. 2020;9(3):734.","journal-title":"J Clin Med"},{"issue":"3","key":"6182_CR36","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1093\/hmg\/8.3.459","volume":"8","author":"TH-M Huang","year":"1999","unstructured":"Huang TH-M, Perry MR, Laux DE. Methylation profiling of cpg islands in human breast cancer cells. Human Molecular Genet. 1999;8(3):459\u201370.","journal-title":"Human Molecular Genet"},{"issue":"6","key":"6182_CR37","doi-asserted-by":"publisher","first-page":"1975","DOI":"10.1158\/0008-5472.CAN-03-3972","volume":"64","author":"S Yegnasubramanian","year":"2004","unstructured":"Yegnasubramanian S, Kowalski J, Gonzalgo ML, Zahurak M, Piantadosi S, Walsh PC, Bova GS, De Marzo AM, Isaacs WB, Nelson WG. Hypermethylation of cpg islands in primary and metastatic human prostate cancer. Cancer Res. 2004;64(6):1975\u201386.","journal-title":"Cancer Res"},{"issue":"11","key":"6182_CR38","doi-asserted-by":"publisher","first-page":"1250","DOI":"10.1038\/cr.2015.126","volume":"25","author":"L Wen","year":"2015","unstructured":"Wen L, Li J, Guo H, Liu X, Zheng S, Zhang D, Zhu W, Qu J, Guo L, Du D. Genome-scale detection of hypermethylated cpg islands in circulating cell-free dna of hepatocellular carcinoma patients. Cell Res. 2015;25(11):1250\u201364.","journal-title":"Cell Res"},{"key":"6182_CR39","doi-asserted-by":"crossref","unstructured":"Silva Rodrigues G, Noronha NY, Almeida ML, Sobrinho ACDS, Watanabe LM, Pinhel MADS, Lima JG, Zhang R, Nonino CB, Alves CR et al. Exercise training modifies the whole-blood methylation profile in middle-aged and older women. J Appl Physiol (2023)","DOI":"10.1152\/japplphysiol.00237.2022"},{"issue":"9","key":"6182_CR40","doi-asserted-by":"publisher","first-page":"0239196","DOI":"10.1371\/journal.pone.0239196","volume":"15","author":"R Mitsumori","year":"2020","unstructured":"Mitsumori R, Sakaguchi K, Shigemizu D, Mori T, Akiyama S, Ozaki K, Niida S, Shimoda N. Lower dna methylation levels in cpg island shores of cr1, clu, and picalm in the blood of japanese alzheimer\u2019s disease patients. PLoS One. 2020;15(9):0239196.","journal-title":"PLoS One"}],"container-title":["BMC Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-025-06182-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12859-025-06182-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-025-06182-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,7]],"date-time":"2025-09-07T16:21:05Z","timestamp":1757262065000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/s12859-025-06182-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,21]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["6182"],"URL":"https:\/\/doi.org\/10.1186\/s12859-025-06182-5","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.01.20.576080","asserted-by":"object"}]},"ISSN":["1471-2105"],"issn-type":[{"value":"1471-2105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,21]]},"assertion":[{"value":"15 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 June 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 July 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no Conflict of interest. AutoX Technologies played no role in the design, development, execution, or interpretation of this study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"188"}}