{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T11:26:36Z","timestamp":1782818796093,"version":"3.54.5"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T00:00:00Z","timestamp":1709769600000},"content-version":"vor","delay-in-days":6,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007128","name":"Natural Science Foundation of Shaanxi Province","doi-asserted-by":"publisher","award":["2024JC-YBMS-783"],"award-info":[{"award-number":["2024JC-YBMS-783"]}],"id":[{"id":"10.13039\/501100007128","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["xzy012022087"],"award-info":[{"award-number":["xzy012022087"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Motivation<\/jats:title><jats:p>Topologically associating domains (TADs) are fundamental building blocks of 3D genome. TAD-like domains in single cells are regarded as the underlying genesis of TADs discovered in bulk cells. Understanding the organization of TAD-like domains helps to get deeper insights into their regulatory functions. Unfortunately, it remains a challenge to identify TAD-like domains on single-cell Hi-C data due to its ultra-sparsity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We propose scKTLD, an in silico tool for the identification of TAD-like domains on single-cell Hi-C data. It takes Hi-C contact matrix as the adjacency matrix for a graph, embeds the graph structures into a low-dimensional space with the help of sparse matrix factorization followed by spectral propagation, and the TAD-like domains can be identified using a kernel-based changepoint detection in the embedding space. The results tell that our scKTLD is superior to the other methods on the sparse contact matrices, including downsampled bulk Hi-C data as well as simulated and experimental single-cell Hi-C data. Besides, we demonstrated the conservation of TAD-like domain boundaries at single-cell level apart from heterogeneity within and across cell types, and found that the boundaries with higher frequency across single cells are more enriched for architectural proteins and chromatin marks, and they preferentially occur at TAD boundaries in bulk cells, especially at those with higher hierarchical levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Availability and implementation<\/jats:title><jats:p>scKTLD is freely available at https:\/\/github.com\/lhqxinghun\/scKTLD.<\/jats:p><\/jats:sec>","DOI":"10.1093\/bioinformatics\/btae138","type":"journal-article","created":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T06:02:35Z","timestamp":1709791355000},"source":"Crossref","is-referenced-by-count":7,"title":["Identifying TAD-like domains on single-cell Hi-C data by graph embedding and changepoint detection"],"prefix":"10.1093","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3271-0683","authenticated-orcid":false,"given":"Erhu","family":"Liu","sequence":"first","affiliation":[{"name":"School of Information and Control Engineering, Xi'an University of Architecture and Technology , Xi'an 710055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5061-4762","authenticated-orcid":false,"given":"Hongqiang","family":"Lyu","sequence":"additional","affiliation":[{"name":"School of Automation Science and Engineering, Faculty of Electronic and Information Engineering, Xi\u2019an Jiaotong University , Xi'an 710049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Automation Science and Engineering, Faculty of Electronic and Information Engineering, Xi\u2019an Jiaotong University , Xi'an 710049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9086-3982","authenticated-orcid":false,"given":"Laiyi","family":"Fu","sequence":"additional","affiliation":[{"name":"School of Automation Science and Engineering, Faculty of Electronic and Information Engineering, Xi\u2019an Jiaotong University , Xi'an 710049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoliang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The First Affiliated Hospital of Xi\u2019an Jiaotong University , Xi'an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoran","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Oncology, The Second Affiliated Hospital of Xi\u2019an Jiaotong University , Xi'an 710004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,3,6]]},"reference":[{"key":"2024032405155391500_btae138-B1","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1186\/s13059-019-1893-y","article-title":"OnTAD: hierarchical domain structure reveals the divergence of activity among TADs and boundaries","volume":"20","author":"An","year":"2019","journal-title":"Genome Biol"},{"key":"2024032405155391500_btae138-B2","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1137\/120875338","article-title":"A Cheeger inequality for the graph connection Laplacian","volume":"34","author":"Bandeira","year":"2013","journal-title":"SIAM J Matrix Anal Appl"},{"key":"2024032405155391500_btae138-B3","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.ymeth.2012.04.004","article-title":"Genome structure determination via 3C-based data integration by the integrative modeling platform","volume":"58","author":"Bau","year":"2012","journal-title":"Methods"},{"key":"2024032405155391500_btae138-B4","doi-asserted-by":"crossref","first-page":"eaau1783","DOI":"10.1126\/science.aau1783","article-title":"Super-resolution chromatin tracing reveals domains and cooperative interactions in single cells","volume":"362","author":"Bintu","year":"2018","journal-title":"Science"},{"key":"2024032405155391500_btae138-B5","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/nrg.2016.112","article-title":"Organization and function of the 3D genome","volume":"17","author":"Bonev","year":"2016","journal-title":"Nat Rev Genet"},{"key":"2024032405155391500_btae138-B6","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1093\/bioinformatics\/btw221","article-title":"Spectral identification of topological domains","volume":"32","author":"Chen","year":"2016","journal-title":"Bioinformatics"},{"key":"2024032405155391500_btae138-B7","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1038\/nature14450","article-title":"Condensin-driven remodelling of X chromosome topology during dosage compensation","volume":"523","author":"Crane","year":"2015","journal-title":"Nature"},{"key":"2024032405155391500_btae138-B8","first-page":"1","article-title":"SpectralTAD: an R package for defining a hierarchy of topologically associated domains using spectral clustering","volume":"21","author":"Cresswell","year":"2020","journal-title":"BMC Bioinf"},{"key":"2024032405155391500_btae138-B9","doi-asserted-by":"crossref","first-page":"2994","DOI":"10.1093\/nar\/gkx145","article-title":"A critical assessment of topologically associating domain prediction tools","volume":"45","author":"Dali","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"2024032405155391500_btae138-B10","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/nature23884","article-title":"The 4D nucleome project","volume":"549","author":"Dekker","year":"2017","journal-title":"Nature"},{"key":"2024032405155391500_btae138-B11","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1016\/j.cell.2016.02.007","article-title":"The 3D genome as moderator of chromosomal communication","volume":"164","author":"Dekker","year":"2016","journal-title":"Cell"},{"key":"2024032405155391500_btae138-B12","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.molcel.2016.05.018","article-title":"Chromatin domains: the unit of chromosome organization","volume":"62","author":"Dixon","year":"2016","journal-title":"Mol Cell"},{"key":"2024032405155391500_btae138-B13","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1038\/nature11082","article-title":"Topological domains in mammalian genomes identified by analysis of chromatin interactions","volume":"485","author":"Dixon","year":"2012","journal-title":"Nature"},{"key":"2024032405155391500_btae138-B14","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nature11247","article-title":"An integrated encyclopedia of DNA elements in the human genome","volume":"489","year":"2012","journal-title":"Nature"},{"key":"2024032405155391500_btae138-B15","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.cels.2016.07.002","article-title":"Juicer provides a one-click system for analyzing loop-resolution Hi-C experiments","volume":"3","author":"Durand","year":"2016","journal-title":"Cell Syst"},{"key":"2024032405155391500_btae138-B16","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1038\/nature16490","article-title":"Insulator dysfunction and oncogene activation in IDH mutant gliomas","volume":"529","author":"Flavahan","year":"2016","journal-title":"Nature"},{"key":"2024032405155391500_btae138-B17","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/nmeth.4325","article-title":"Comparison of computational methods for Hi-C data analysis","volume":"14","author":"Forcato","year":"2017","journal-title":"Nat Methods"},{"key":"2024032405155391500_btae138-B18","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/nature19800","article-title":"Formation of new chromatin domains determines pathogenicity of genomic duplications","volume":"538","author":"Franke","year":"2016","journal-title":"Nature"},{"key":"2024032405155391500_btae138-B19","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1137\/090771806","article-title":"Finding structure with randomness: probabilistic algorithms for constructing approximate matrix decompositions","volume":"53","author":"Halko","year":"2011","journal-title":"SIAM Rev"},{"key":"2024032405155391500_btae138-B20","first-page":"768","author":"Harchaoui","year":"2007"},{"key":"2024032405155391500_btae138-B21","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1126\/science.aad9024","article-title":"Activation of proto-oncogenes by disruption of chromosome neighborhoods","volume":"351","author":"Hnisz","year":"2016","journal-title":"Science"},{"key":"2024032405155391500_btae138-B22","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.molcel.2012.08.031","article-title":"Gene density, transcription, and insulators contribute to the partition of the drosophila genome into physical domains","volume":"48","author":"Hou","year":"2012","journal-title":"Mol Cell"},{"key":"2024032405155391500_btae138-B23","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1080\/01621459.2012.737745","article-title":"Optimal detection of changepoints with a linear computational cost","volume":"107","author":"Killick","year":"2012","journal-title":"J Am Stat Assoc"},{"key":"2024032405155391500_btae138-B24","doi-asserted-by":"crossref","DOI":"10.4135\/9781412985130","volume-title":"Multidimensional Scaling","author":"Kruskal","year":"1978"},{"key":"2024032405155391500_btae138-B25","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1101\/gad.241422.114","article-title":"Distinct structural transitions of chromatin topological domains correlate with coordinated hormone-induced gene regulation","volume":"28","author":"Le Dily","year":"2014","journal-title":"Genes Dev"},{"key":"2024032405155391500_btae138-B26","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1186\/s13059-021-02378-z","article-title":"GRiNCH: simultaneous smoothing and detection of topological units of genome organization from sparse chromatin contact count matrices with matrix factorization","volume":"22","author":"Lee","year":"2021","journal-title":"Genome Biol"},{"key":"2024032405155391500_btae138-B27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1145\/2665063","article-title":"Multiway spectral partitioning and higher-order cheeger inequalities","volume":"61","author":"Lee","year":"2014","journal-title":"J ACM"},{"key":"2024032405155391500_btae138-B28","doi-asserted-by":"crossref","first-page":"3265","DOI":"10.1038\/s41467-018-05691-7","article-title":"Decoding topologically associating domains with ultra-low resolution Hi-C data by graph structural entropy","volume":"9","author":"Li","year":"2018","journal-title":"Nat Commun"},{"key":"2024032405155391500_btae138-B29","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.ymeth.2019.08.005","article-title":"Comparison of computational methods for 3D genome analysis at single-cell Hi-C level","volume":"181\u2013182","author":"Li","year":"2020","journal-title":"Methods"},{"key":"2024032405155391500_btae138-B30","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1186\/s13059-021-02435-7","article-title":"DeTOKI identifies and characterizes the dynamics of chromatin TAD-like domains in a single cell","volume":"22","author":"Li","year":"2021","journal-title":"Genome Biol"},{"key":"2024032405155391500_btae138-B31","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1126\/science.1181369","article-title":"Comprehensive mapping of long range interactions reveals folding principles of the human genome","volume":"326","author":"Liebermanaiden","year":"2009","journal-title":"Science"},{"key":"2024032405155391500_btae138-B32","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1038\/s42003-022-03546-y","article-title":"TADfit is a multivariate linear regression model for profiling hierarchical chromatin domains on replicate Hi-C data","volume":"5","author":"Liu","year":"2022","journal-title":"Commun Biol"},{"key":"2024032405155391500_btae138-B33","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1109\/TCBB.2022.3147805","article-title":"A comparison of topologically associating domain callers based on Hi-C data","volume":"20","author":"Liu","year":"2023","journal-title":"IEEE\/ACM Trans Comput Biol Bioinform"},{"key":"2024032405155391500_btae138-B34","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1016\/j.cell.2015.04.004","article-title":"Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions","volume":"161","author":"Lupi\u00e1\u00f1ez","year":"2015","journal-title":"Cell"},{"key":"2024032405155391500_btae138-B35","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.tig.2016.01.003","article-title":"Breaking TADs: how alterations of chromatin domains result in disease","volume":"32","author":"Lupi\u00e1\u00f1ez","year":"2016","journal-title":"Trends Genet"},{"key":"2024032405155391500_btae138-B36","doi-asserted-by":"crossref","first-page":"56","DOI":"10.2144\/btn-2019-0105","article-title":"Comparison of normalization methods for Hi-C data","volume":"68","author":"Lyu","year":"2020","journal-title":"BioTechniques"},{"key":"2024032405155391500_btae138-B37","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1038\/s41580-019-0162-y","article-title":"Control of DNA replication timing in the 3D genome","volume":"20","author":"Marchal","year":"2019","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2024032405155391500_btae138-B38","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/nature12593","article-title":"Single-cell Hi-C reveals cell-to-cell variability in chromosome structure","volume":"502","author":"Nagano","year":"2013","journal-title":"Nature"},{"key":"2024032405155391500_btae138-B39","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/nature23001","article-title":"Cell-cycle dynamics of chromosomal organization at single-cell resolution","volume":"547","author":"Nagano","year":"2017","journal-title":"Nature"},{"key":"2024032405155391500_btae138-B40","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/nature11049","article-title":"Spatial partitioning of the regulatory landscape of the X-inactivation centre","volume":"485","author":"Nora","year":"2012","journal-title":"Nature"},{"key":"2024032405155391500_btae138-B41","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/nmeth.4560","article-title":"Detecting hierarchical genome folding with network modularity","volume":"15","author":"Norton","year":"2018","journal-title":"Nat Methods"},{"key":"2024032405155391500_btae138-B42","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1186\/s12859-017-1931-2","article-title":"ClusterTAD: an unsupervised machine learning approach to detecting topologically associated domains of chromosomes from Hi-C data","volume":"18","author":"Oluwadare","year":"2017","journal-title":"BMC Bioinf"},{"key":"2024032405155391500_btae138-B43","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1016\/j.cell.2014.11.021","article-title":"A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping","volume":"159","author":"Rao","year":"2014","journal-title":"Cell"},{"key":"2024032405155391500_btae138-B44","doi-asserted-by":"crossref","first-page":"e1005665","DOI":"10.1371\/journal.pcbi.1005665","article-title":"Automatic analysis and 3D-modelling of Hi-C data using TADbit reveals structural features of the fly chromatin colors","volume":"13","author":"Serra","year":"2017","journal-title":"PLoS Comput Biol"},{"key":"2024032405155391500_btae138-B45","doi-asserted-by":"crossref","first-page":"e70","DOI":"10.1093\/nar\/gkv1505","article-title":"TopDom: an efficient and deterministic method for identifying topological domains in genomes","volume":"44","author":"Shin","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"2024032405155391500_btae138-B46","doi-asserted-by":"crossref","first-page":"e39","DOI":"10.1093\/nar\/gkaa087","article-title":"Hierarchical chromatin organization detected by TADpole","volume":"48","author":"Solervila","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"2024032405155391500_btae138-B47","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1126\/science.aat5641","article-title":"Three-dimensional genome structures of single diploid human cells","volume":"361","author":"Tan","year":"2018","journal-title":"Science"},{"key":"2024032405155391500_btae138-B48","doi-asserted-by":"crossref","first-page":"107299","DOI":"10.1016\/j.sigpro.2019.107299","article-title":"Selective review of offline change point detection methods","volume":"167","author":"Truong","year":"2020","journal-title":"Signal Process"},{"key":"2024032405155391500_btae138-B49","doi-asserted-by":"crossref","first-page":"e163","DOI":"10.1093\/nar\/gkx735","article-title":"HiTAD: detecting the structural and functional hierarchies of topologically associating domains from chromatin interactions","volume":"45","author":"Wang","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"2024032405155391500_btae138-B50","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1093\/bioinformatics\/btv485","article-title":"Identification of hierarchical chromatin domains","volume":"32","author":"Weinreb","year":"2016","journal-title":"Bioinformatics"},{"key":"2024032405155391500_btae138-B51","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s13059-019-1658-7","article-title":"Measuring the reproducibility and quality of Hi-C data","volume":"20","author":"Yard\u0131mc\u0131","year":"2019","journal-title":"Genome Biol"},{"key":"2024032405155391500_btae138-B52","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/s41467-017-00478-8","article-title":"Identifying topologically associating domains and subdomains by gaussian mixture model and proportion test","volume":"8","author":"Yu","year":"2017","journal-title":"Nat Commun"},{"key":"2024032405155391500_btae138-B53","first-page":"4278","author":"Zhang","year":"2019"},{"key":"2024032405155391500_btae138-B54","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1038\/s41587-021-01034-y","article-title":"Multiscale and integrative single-cell Hi-C analysis with higashi","volume":"40","author":"Zhang","year":"2022","journal-title":"Nat Biotechnol"},{"key":"2024032405155391500_btae138-B55","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13059-020-02234-6","article-title":"SuperTAD: robust detection of hierarchical topologically associated domains with optimized structural information","volume":"22","author":"Zhang","year":"2021","journal-title":"Genome Biol"},{"key":"2024032405155391500_btae138-B56","doi-asserted-by":"crossref","first-page":"14011","DOI":"10.1073\/pnas.1901423116","article-title":"Robust single-cell Hi-C clustering by convolution-and random-walk\u2013based imputation","volume":"116","author":"Zhou","year":"2019","journal-title":"Proc Natl Acad Sci USA"},{"key":"2024032405155391500_btae138-B57","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1186\/s13059-018-1596-9","article-title":"Comparison of computational methods for the identification of topologically associating domains","volume":"19","author":"Zufferey","year":"2018","journal-title":"Genome Biol"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btae138\/56887322\/btae138.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/40\/3\/btae138\/57075969\/btae138.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/40\/3\/btae138\/57075969\/btae138.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T21:12:59Z","timestamp":1731532379000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/doi\/10.1093\/bioinformatics\/btae138\/7623584"}},"subtitle":[],"editor":[{"given":"Janet","family":"Kelso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,3,1]]},"references-count":57,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3,4]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btae138","relation":{},"ISSN":["1367-4811"],"issn-type":[{"value":"1367-4811","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,3,1]]},"published":{"date-parts":[[2024,3,1]]},"article-number":"btae138"}}