{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T02:22:36Z","timestamp":1784254956812,"version":"3.55.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2023,6,29]],"date-time":"2023-06-29T00:00:00Z","timestamp":1687996800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["12271522"],"award-info":[{"award-number":["12271522"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["11901575"],"award-info":[{"award-number":["11901575"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["12131020"],"award-info":[{"award-number":["12131020"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31930022"],"award-info":[{"award-number":["31930022"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["T2341007"],"award-info":[{"award-number":["T2341007"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["T2350003"],"award-info":[{"award-number":["T2350003"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Simultaneous profiling of multi-omics single-cell data represents exciting technological advancements for understanding cellular states and heterogeneity. Cellular indexing of transcriptomes and epitopes by sequencing allowed for parallel quantification of cell-surface protein expression and transcriptome profiling in the same cells; methylome and transcriptome sequencing from single cells allows for analysis of transcriptomic and epigenomic profiling in the same individual cells. However, effective integration method for mining the heterogeneity of cells over the noisy, sparse, and complex multi-modal data is in growing need.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In this article, we propose a multi-modal high-order neighborhood Laplacian matrix optimization framework for integrating the multi-omics single-cell data: scHoML. Hierarchical clustering method was presented for analyzing the optimal embedding representation and identifying cell clusters in a robust manner. This novel method by integrating high-order and multi-modal Laplacian matrices would robustly represent the complex data structures and allow for systematic analysis at the multi-omics single-cell level, thus promoting further biological discoveries.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>Matlab code is available at https:\/\/github.com\/jianghruc\/scHoML.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btad414","type":"journal-article","created":{"date-parts":[[2023,6,29]],"date-time":"2023-06-29T14:28:35Z","timestamp":1688048915000},"source":"Crossref","is-referenced-by-count":7,"title":["Robust joint clustering of multi-omics single-cell data via multi-modal high-order neighborhood Laplacian matrix optimization"],"prefix":"10.1093","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5891-6044","authenticated-orcid":false,"given":"Hao","family":"Jiang","sequence":"first","affiliation":[{"name":"School of Mathematics, Renmin University of China , Beijing 100872, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senwen","family":"Zhan","sequence":"additional","affiliation":[{"name":"School of Mathematics, Renmin University of China , Beijing 100872, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai-Ki","family":"Ching","sequence":"additional","affiliation":[{"name":"Department of Mathematics, The University of Hong Kong , Pokfulam Road , Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3960-0068","authenticated-orcid":false,"given":"Luonan","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Systems Biology, Shanghai Institute of Biochemistry and Cell Biology, CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences , Shanghai 200031, China"},{"name":"Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Chinese Academy of Sciences , Hangzhou 310024, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,6,29]]},"reference":[{"key":"2023091307360130800_btad414-B1","doi-asserted-by":"crossref","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":"2023091307360130800_btad414-B2","doi-asserted-by":"crossref","first-page":"i48","DOI":"10.1093\/bioinformatics\/btaa443","article-title":"Unsupervised topological alignment for single-cell multi-omics integration","volume":"36","author":"Cao","year":"2020","journal-title":"Bioinformatics"},{"key":"2023091307360130800_btad414-B3","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1038\/s41587-022-01284-4","article-title":"Multi-omics single-cell data integration and regulatory inference with graph-linked embedding","volume":"40","author":"Cao","year":"2022","journal-title":"Nat Biotechnol"},{"key":"2023091307360130800_btad414-B4","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1093\/bioinformatics\/btaa908","article-title":"Single-cell RNA-seq data semi-supervised clustering and annotation via structural regularized domain adaptation","volume":"37","author":"Chen","year":"2021","journal-title":"Bioinformatics"},{"key":"2023091307360130800_btad414-B5","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1093\/bioinformatics\/btac099","article-title":"scGAC: a graph attentional architecture for clustering single-cell RNA-seq data","volume":"38","author":"Cheng","year":"2022","journal-title":"Bioinformatics"},{"key":"2023091307360130800_btad414-B6","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.devcel.2020.02.016","article-title":"Potently cytotoxic natural killer cells initially emerge from erythro-myeloid progenitors during mammalian development","volume":"53","author":"Dege","year":"2020","journal-title":"Dev Cell"},{"key":"2023091307360130800_btad414-B7","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.omto.2020.12.003","article-title":"Single-cell RNA-sequencing analyses identify heterogeneity of CD8+ T cell subpopulations and novel therapy targets in melanoma","volume":"20","author":"Deng","year":"2021","journal-title":"Mol Ther Oncolytics"},{"key":"2023091307360130800_btad414-B8","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1186\/s13059-022-02786-9","article-title":"Regulatory analysis of single cell multiome gene expression and chromatin accessibility data with scREG","volume":"23","author":"Duren","year":"2022","journal-title":"Genome Biol"},{"key":"2023091307360130800_btad414-B9","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1101\/gr.228080.117","article-title":"Linking transcriptional and genetic tumor heterogeneity through allele analysis of single-cell RNA-seq data","volume":"28","author":"Fan","year":"2018","journal-title":"Genome Res"},{"key":"2023091307360130800_btad414-B10","doi-asserted-by":"crossref","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","article-title":"Integrated analysis of multimodal single-cell data","volume":"184","author":"Hao","year":"2021","journal-title":"Cell"},{"key":"2023091307360130800_btad414-B11","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/s13059-016-0938-8","article-title":"Cel-seq2: sensitive highly-multiplexed single-cell RNA-seq","volume":"17","author":"Hashimshony","year":"2016","journal-title":"Genome Biol"},{"key":"2023091307360130800_btad414-B12","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1016\/j.celrep.2012.08.003","article-title":"CEL-seq: single-cell RNA-seq by multiplexed linear amplification","volume":"2","author":"Hashimshony","year":"2012","journal-title":"Cell Rep"},{"key":"2023091307360130800_btad414-B13","first-page":"773","author":"Huang","year":"2012"},{"key":"2023091307360130800_btad414-B14","doi-asserted-by":"crossref","first-page":"3684","DOI":"10.1093\/bioinformatics\/bty390","article-title":"Single cell clustering based on cell-pair differentiability correlation and variance analysis","volume":"34","author":"Jiang","year":"2018","journal-title":"Bioinformatics"},{"key":"2023091307360130800_btad414-B15","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s13059-020-1932-8","article-title":"scAI: an unsupervised approach for the integrative analysis of parallel single-cell transcriptomic and epigenomic profiles","volume":"21","author":"Jin","year":"2020","journal-title":"Genome Biol"},{"key":"2023091307360130800_btad414-B16","doi-asserted-by":"crossref","first-page":"2866","DOI":"10.1038\/s41467-021-23189-7","article-title":"IL-21 and IFN\u03b1 therapy rescues terminally differentiated NK cells and limits SIV reservoir in ART-treated macaques","volume":"12","author":"Harper","year":"2021","journal-title":"Nat Commun"},{"key":"2023091307360130800_btad414-B17","first-page":"393","author":"Kumar","year":"2011"},{"key":"2023091307360130800_btad414-B18","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.immuni.2015.02.013","article-title":"Epigenetic modification and antibody-dependent expansion of memory-like NK cells in human cytomegalovirus-infected individuals","volume":"42","author":"Lee","year":"2015","journal-title":"Immunity"},{"key":"2023091307360130800_btad414-B19","first-page":"12344","author":"Liu","year":"2021"},{"key":"2023091307360130800_btad414-B20","doi-asserted-by":"crossref","first-page":"3235","DOI":"10.1093\/bioinformatics\/btab276","article-title":"Clustering single-cell RNA-seq data by rank constrained similarity learning","volume":"37","author":"Mei","year":"2021","journal-title":"Bioinformatics"},{"key":"2023091307360130800_btad414-B21","first-page":"1881","author":"Nie","year":"2016"},{"key":"2023091307360130800_btad414-B22","first-page":"2022","author":"Nie","year":"2018"},{"key":"2023091307360130800_btad414-B23","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1038\/s41422-019-0195-y","article-title":"Single-cell RNA-seq highlights intra-tumoral heterogeneity and malignant progression in pancreatic ductal adenocarcinoma","volume":"29","author":"Peng","year":"2019","journal-title":"Cell Res"},{"key":"2023091307360130800_btad414-B24","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/nprot.2014.006","article-title":"Full-length RNA-seq from single cells using Smart-seq2","volume":"9","author":"Picelli","year":"2014","journal-title":"Nat Protoc"},{"key":"2023091307360130800_btad414-B25","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1038\/nbt.2282","article-title":"Full-length mRNA-seq from single-cell levels of RNA and individual circulating tumor cells","volume":"30","author":"Ramsk\u00f6ld","year":"2012","journal-title":"Nat Biotechnol"},{"key":"2023091307360130800_btad414-B26","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1016\/j.cell.2021.01.053","article-title":"Covid-19 immune features revealed by a large-scale single-cell transcriptome atlas","volume":"184","author":"Ren","year":"2021","journal-title":"Cell"},{"key":"2023091307360130800_btad414-B27","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s13059-021-02301-6","article-title":"Pluripotent stem cell derived models of neurological diseases reveal early transcriptional heterogeneity","volume":"22","author":"Sorek","year":"2021","journal-title":"Genome Biol"},{"key":"2023091307360130800_btad414-B28","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1038\/nmeth.4380","article-title":"Simultaneous epitope and transcriptome measurement in single cells","volume":"14","author":"Stoeckius","year":"2017","journal-title":"Nat Methods"},{"key":"2023091307360130800_btad414-B29","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","article-title":"Comprehensive integration of single-cell data","volume":"177","author":"Stuart","year":"2019","journal-title":"Cell"},{"key":"2023091307360130800_btad414-B30","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/nmeth.1315","article-title":"mRNA-seq whole-transcriptome analysis of a single cell","volume":"6","author":"Tang","year":"2009","journal-title":"Nat Methods"},{"key":"2023091307360130800_btad414-B31","doi-asserted-by":"crossref","first-page":"5814","DOI":"10.1093\/nar\/gkaa314","article-title":"BREM-SC: a Bayesian random effects mixture model for joint clustering single cell multi-omics data","volume":"48","author":"Wang","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"2023091307360130800_btad414-B32","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1186\/s13059-017-1269-0","article-title":"Matcher: manifold alignment reveals correspondence between single cell transcriptome and epigenome dynamics","volume":"18","author":"Welch","year":"2017","journal-title":"Genome Biol"},{"key":"2023091307360130800_btad414-B33","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.1016\/j.cell.2019.05.006","article-title":"Single-cell multi-omic integration compares and contrasts features of brain cell identity","volume":"177","author":"Welch","year":"2019","journal-title":"Cell"},{"key":"2023091307360130800_btad414-B34","author":"Xia","year":"2014"},{"key":"2023091307360130800_btad414-B35","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1109\/TSMCB.2009.2039566","article-title":"Multiview spectral embedding","volume":"40","author":"Xia","year":"2010","journal-title":"IEEE Trans Syst Man Cybernet B Cybernet"},{"key":"2023091307360130800_btad414-B36","doi-asserted-by":"crossref","first-page":"7723","DOI":"10.1073\/pnas.1805681115","article-title":"Integrative analysis of single-cell genomics data by coupled nonnegative matrix factorizations","volume":"115","author":"Zhana","year":"2018","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023091307360130800_btad414-B37","doi-asserted-by":"crossref","first-page":"12112","DOI":"10.1093\/nar\/gkac1109","article-title":"scAB detects multiresolution cell states with clinical significance by integrating single-cell genomics and bulk sequencing data","volume":"50","author":"Zhang","year":"2022","journal-title":"Nucleic Acids Res"},{"key":"2023091307360130800_btad414-B38","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1038\/s41586-018-0694-x","article-title":"Lineage tracking reveals dynamic relationships of t cells in colorectal cancer","volume":"564","author":"Zhang","year":"2018","journal-title":"Nature"},{"key":"2023091307360130800_btad414-B40","first-page":"6965","author":"Zhou","year":"2020"},{"key":"2023091307360130800_btad414-B41","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1126\/science.1229164","article-title":"Genome-wide detection of single-nucleotide and copy-number variations of a single human cell","volume":"338","author":"Zong","year":"2012","journal-title":"Science"},{"key":"2023091307360130800_btad414-B42","doi-asserted-by":"crossref","first-page":"3964","DOI":"10.1093\/bioinformatics\/btab420","article-title":"HGC: fast hierarchical clustering for large-scale single-cell data","volume":"37","author":"Zou","year":"2021","journal-title":"Bioinformatics"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btad414\/50739851\/btad414.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/39\/7\/btad414\/51538487\/btad414.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/39\/7\/btad414\/51538487\/btad414.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T07:36:54Z","timestamp":1694590614000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/doi\/10.1093\/bioinformatics\/btad414\/7210258"}},"subtitle":[],"editor":[{"given":"Jonathan","family":"Wren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,6,29]]},"references-count":41,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2023,7,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btad414","relation":{},"ISSN":["1367-4811"],"issn-type":[{"value":"1367-4811","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,7,1]]},"published":{"date-parts":[[2023,6,29]]},"article-number":"btad414"}}