{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T12:19:32Z","timestamp":1784290772672,"version":"3.55.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000},"content-version":"vor","delay-in-days":27,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Fundamental Research Funds for Public Universities in Liaoning","award":["LJ242410140009"],"award-info":[{"award-number":["LJ242410140009"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62002056"],"award-info":[{"award-number":["62002056"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Training Program of Innovation and Entrepreneurship for Undergraduates","award":["S202410145029"],"award-info":[{"award-number":["S202410145029"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>DNA methylation is a key epigenetic modification involved in biological processes and disease development. The accurate analysis of DNA methylation site information is of significant biological importance. Despite advances in single-cell sequencing, data sparsity due to low cytosine-phosphate-guanine (CpG) coverage remains a challenge. To address this, we introduce MambaCpG, a single-cell DNA methylation state imputation model based on the Mamba block. MambaCpG integrates the methylation matrix and DNA sequence context and uses bidirectional Mamba blocks to obtain embeddings, effectively capturing the long-range dependencies between CpG sites within DNA methylation patterns. Experiments on seven datasets of various scales demonstrate that MambaCpG outperforms existing models on large, highly sparse datasets while showing competitive performance on smaller datasets. MambaCpG has lower parameter and memory requirements, making it suitable for practical applications. MambaCpG also reveals ultra-long-range dependencies and provides new insights into DNA methylation patterning.<\/jats:p>","DOI":"10.1093\/bib\/bbaf360","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T03:58:51Z","timestamp":1753675131000},"source":"Crossref","is-referenced-by-count":4,"title":["MambaCpG: an accurate model for single-cell DNA methylation status imputation using mamba"],"prefix":"10.1093","volume":"26","author":[{"given":"Qi","family":"Zhao","sequence":"first","affiliation":[{"name":"Faculty of Information, Liaoning University , Chongshan Middle Road 66, 110036 Liaoning ,","place":["China"]},{"name":"College of Medicine and Biological Information Engineering, Northeastern University , Wenhua Road 3, 110000 Liaoning ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ze","family":"Li","sequence":"additional","affiliation":[{"name":"College of Medicine and Biological Information Engineering, Northeastern University , Wenhua Road 3, 110000 Liaoning ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Mao","sequence":"additional","affiliation":[{"name":"College of Light Industry, Liaoning University , Chongshan Middle Road 66, 110036 Liaoning ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingwei","family":"Chen","sequence":"additional","affiliation":[{"name":"Faculty of Information, Liaoning University , Chongshan Middle Road 66, 110036 Liaoning ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiran","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Medicine and Biological Information Engineering, Northeastern University , Wenhua Road 3, 110000 Liaoning ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingle","family":"Li","sequence":"additional","affiliation":[{"name":"College of Medicine and Biological Information Engineering, Northeastern University , Wenhua Road 3, 110000 Liaoning ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Artificial Intelligence , Dalian Maritime University, Linghai Road #1, 116026 Liaoning,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoya","family":"Fan","sequence":"additional","affiliation":[{"name":"School of Software, Dalian University of Technology , No. 2 Linggong Road, 116024 Liaoning ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,7,28]]},"reference":[{"key":"2025072723584500600_ref1","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1016\/j.tig.2022.03.010","article-title":"DNA methylation: a historical perspective","volume":"38","author":"Mattei","year":"2022","journal-title":"Trends Genet"},{"key":"2025072723584500600_ref2","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1038\/npp.2012.112","article-title":"DNA methylation and its basic function","volume":"38","author":"Moore","year":"2013","journal-title":"Neuropsychopharmacology"},{"key":"2025072723584500600_ref3","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1038\/nmeth.3728","article-title":"Parallel single-cell sequencing links transcriptional and epigenetic heterogeneity","volume":"13","author":"Angermueller","year":"2016","journal-title":"Nat Methods"},{"key":"2025072723584500600_ref4","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1038\/nmeth.3035","article-title":"Single-cell genome-wide bisulfite sequencing for assessing epigenetic heterogeneity","volume":"11","author":"Smallwood","year":"2014","journal-title":"Nat Methods"},{"key":"2025072723584500600_ref5","doi-asserted-by":"publisher","first-page":"2126","DOI":"10.1101\/gr.161679.113","article-title":"Single-cell methylome landscapes of mouse embryonic stem cells and early embryos analyzed using reduced representation bisulfite sequencing","volume":"23","author":"Guo","year":"2013","journal-title":"Genome Res"},{"key":"2025072723584500600_ref6","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1126\/science.aan3351","article-title":"Single-cell methylomes identify neuronal subtypes and regulatory elements in mammalian cortex","volume":"357","author":"Luo","year":"2017","journal-title":"Science"},{"key":"2025072723584500600_ref7","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1038\/nprot.2015.039","article-title":"Profiling dna methylome landscapes of mammalian cells with single-cell reduced-representation bisulfite sequencing","volume":"10","author":"Guo","year":"2015","journal-title":"Nat Protoc"},{"key":"2025072723584500600_ref8","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1186\/s12864-019-5654-9","article-title":"LightCpG: a multi-view CpG sites detection on single-cell whole genome sequence data","volume":"20","author":"Jiang","year":"2019","journal-title":"BMC Genomics"},{"key":"2025072723584500600_ref9","doi-asserted-by":"publisher","DOI":"10.5555\/3294996.3295074","article-title":"Lightgbm: A highly efficient gradient boosting decision tree","author":"Ke","journal-title":"Proceedings of the 31st International Conference on Neural Information Processing Systems (NIPS'17)"},{"key":"2025072723584500600_ref10","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1186\/s13059-019-1665-8","article-title":"Melissa: Bayesian clustering and imputation of single-cell methylomes","volume":"20","author":"Kapourani","year":"2019","journal-title":"Genome Biol"},{"key":"2025072723584500600_ref11","doi-asserted-by":"publisher","first-page":"1814","DOI":"10.1093\/bioinformatics\/btab029","article-title":"Camelia: Imputation in single-cell methylomes based on local similarities between cells","volume":"37","author":"Tang","year":"2021","journal-title":"Bioinformatics"},{"key":"2025072723584500600_ref12","article-title":"CatBoost: gradient boosting with categorical features support","author":"Dorogush"},{"key":"2025072723584500600_ref13","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1186\/s13059-017-1189-z","article-title":"Deepcpg: Accurate prediction of single-cell dna methylation states using deep learning","volume":"18","author":"Angermueller","year":"2017","journal-title":"Genome Biol"},{"key":"2025072723584500600_ref14","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1093\/bioinformatics\/btab746","article-title":"CpG transformer for imputation of single-cell methylomes","volume":"38","author":"De Waele","year":"2022","journal-title":"Bioinformatics"},{"key":"2025072723584500600_ref15","doi-asserted-by":"publisher","journal-title":"Proceedings of the 31st International Conference on Neural Information Processing Systems (NIPS'17)","DOI":"10.5555\/3295222.3295349"},{"key":"2025072723584500600_ref16","doi-asserted-by":"publisher","DOI":"10.18653\/v1\/N19-1423","article-title":"Bert: Pre-training of deep bidirectional transformers for language understanding","author":"Devlin","year":"2018"},{"key":"2025072723584500600_ref17","doi-asserted-by":"publisher","article-title":"Axial attention in multidimensional transformers","author":"Ho","DOI":"10.48550\/arXiv.1912.12180"},{"key":"2025072723584500600_ref18","doi-asserted-by":"publisher","DOI":"10.48550\/arXiv.2004.05150","article-title":"Longformer: the long-document transformer","author":"Beltagy","year":"2020"},{"key":"2025072723584500600_ref19","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btad533","article-title":"GraphCpG: Imputation of single-cell methylomes based on locus-aware neighboring subgraphs","volume":"39","author":"Deng","year":"2023","journal-title":"Bioinformatics"},{"key":"2025072723584500600_ref20","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1007\/978-3-319-93417-4_38","article-title":"Modeling relational data with graph convolutional networks","volume-title":"The Semantic Web: 15th International Conference, ESWC 2018, Heraklion, Crete, Greece, June 3\u20137, 2018, Proceedings 15","author":"Schlichtkrull","year":"2018"},{"key":"2025072723584500600_ref21","doi-asserted-by":"publisher","DOI":"10.48550\/arXiv.2312.00752","article-title":"Linear-time sequence modeling with selective state spaces","author":"Albert","year":"2023"},{"key":"2025072723584500600_ref22","doi-asserted-by":"publisher","DOI":"10.48550\/arXiv.2111.00396","article-title":"Efficiently modeling long sequences with structured state spaces","author":"Albert","year":"2021"},{"key":"2025072723584500600_ref23","doi-asserted-by":"publisher","volume-title":"Proceedings of the 38th International Conference on Neural Information Processing Systems (NIPS '24)","author":"Liu","DOI":"10.48550\/arXiv.2401.10166"},{"key":"2025072723584500600_ref24","doi-asserted-by":"publisher","DOI":"10.48550\/arXiv.2405.11831","article-title":"SSAMBA: self-supervised audio representation learning with Mamba state space model","volume-title":"IEEE Spoken Language Technology Workshop (SLT)","author":"Shams"},{"key":"2025072723584500600_ref25","doi-asserted-by":"publisher","volume-title":"Proceedings of the 41st International Conference on Machine Learning (ICML'24)","author":"Schiff","DOI":"10.48550\/arXiv.2403.03234"},{"key":"2025072723584500600_ref26","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1093\/nar\/30.1.207","article-title":"Gene expression omnibus: NCBI gene expression and hybridization array data repository","volume":"30","author":"Edgar","year":"2002","journal-title":"Nucleic Acids Res"},{"key":"2025072723584500600_ref27","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1038\/cr.2016.23","article-title":"Single-cell triple omics sequencing reveals genetic, epigenetic, and transcriptomic heterogeneity in hepatocellular carcinomas","volume":"26","author":"Hou","year":"2016","journal-title":"Cell Res"},{"key":"2025072723584500600_ref28","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1158\/2643-3230.bcd-19-0058","article-title":"Preneoplastic alterations define CLL DNA methylome and persist through disease progression and therapy","volume":"2","author":"Kretzmer","year":"2021","journal-title":"Blood Cancer Discov"},{"key":"2025072723584500600_ref29","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1016\/j.stem.2016.10.019","article-title":"DNA methylation dynamics of human hematopoietic stem cell differentiation","volume":"19","author":"Farlik","year":"2016","journal-title":"Cell Stem Cell"},{"key":"2025072723584500600_ref30","doi-asserted-by":"publisher","first-page":"63","DOI":"10.48550\/arXiv.1908.11415","volume":"24","journal-title":"IJDAR"},{"key":"2025072723584500600_ref31","doi-asserted-by":"publisher","volume-title":"IEEE Conference on Computer Vision and Pattern Recognition (CVPR)","DOI":"10.1109\/CVPR.2016.90"},{"key":"2025072723584500600_ref32","doi-asserted-by":"publisher","DOI":"10.48550\/arXiv.1607.06450","article-title":"Layer normalization","author":"Ba","year":"2016"},{"key":"2025072723584500600_ref33","doi-asserted-by":"publisher","DOI":"10.48550\/arXiv.1710.05941","article-title":"Searching for activation functions","author":"Ramachandran","year":"2017"},{"key":"2025072723584500600_ref34","doi-asserted-by":"publisher","first-page":"572","DOI":"10.5555\/3540261.3540305","article-title":"Combining recurrent, convolutional, and continuous-time models with linear state space layers","volume":"34","author":"Albert","year":"2021","journal-title":"Advances in neural information processing systems"},{"key":"2025072723584500600_ref35","doi-asserted-by":"publisher","DOI":"10.48550\/arXiv.1608.03983","article-title":"Sgdr: Stochastic gradient descent with warm restarts","author":"Loshchilov","year":"2016"},{"key":"2025072723584500600_ref36","doi-asserted-by":"publisher","DOI":"10.48550\/arXiv.1711.05101","article-title":"Decoupled weight decay regularization","author":"Loshchilov","year":"2017"},{"key":"2025072723584500600_ref37","article-title":"Visualizing data using t-SNE","volume":"9","author":"Van der Maaten","year":"2008","journal-title":"J Mach Learn Res"},{"key":"2025072723584500600_ref38","doi-asserted-by":"publisher","DOI":"10.48550\/arXiv.1802.03426","article-title":"UMAP: uniform manifold approximation and projection for dimension reduction","author":"McInnes","year":"2018"},{"key":"2025072723584500600_ref39","article-title":"Axiomatic attribution for deep networks","volume-title":"Proceedings of the 34th International Conference on Machine Learning (ICML 2017), 6\u201311 Aug 2017, Sydney, Australia. Proceedings of Machine Learning Research","author":"Sundararajan"},{"key":"2025072723584500600_ref40","doi-asserted-by":"publisher","first-page":"e1009189","DOI":"10.1371\/journal.pgen.1009189","article-title":"Rare genetic variation at transcription factor binding sites modulates local dna methylation profiles","volume":"16","author":"Martin-Trujillo","year":"2020","journal-title":"PLoS Genet"}],"container-title":["Briefings in Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bib\/article-pdf\/26\/4\/bbaf360\/63857630\/bbaf360.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bib\/article-pdf\/26\/4\/bbaf360\/63857630\/bbaf360.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T03:58:54Z","timestamp":1753675134000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bib\/article\/doi\/10.1093\/bib\/bbaf360\/8214233"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":40,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,7,2]]}},"URL":"https:\/\/doi.org\/10.1093\/bib\/bbaf360","relation":{},"ISSN":["1467-5463","1477-4054"],"issn-type":[{"value":"1467-5463","type":"print"},{"value":"1477-4054","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,7]]},"published":{"date-parts":[[2025,7]]},"article-number":"bbaf360"}}