{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T11:31:13Z","timestamp":1773315073717,"version":"3.50.1"},"reference-count":81,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"vor","delay-in-days":41,"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":["62131004"],"award-info":[{"award-number":["62131004"]}],"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":["62302342"],"award-info":[{"award-number":["62302342"]}],"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":["62371403"],"award-info":[{"award-number":["62371403"]}],"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":["62371347"],"award-info":[{"award-number":["62371347"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Joint profiling technologies combining single-cell chromatin accessibility (CA) and transcriptome sequencing enable cellular heterogeneity analysis from both gene and cis-regulatory element perspectives, greatly advancing molecular biology at a cellular resolution. These techniques have been used to construct gene regulatory networks across diverse cell types and biological tissues, contributing significantly to the mapping of cell developmental trajectories. In this review, we summarize existing single-cell joint profiling methods for CA and transcriptomics and systematically evaluate the data quality of each modality using consistent criteria: the median number of genes detected per cell (RNA) and the median number of accessible peaks per cell (ATAC). Furthermore, we examine relevant bioinformatics tools and highlight their applications in various omics research contexts. Finally, we discuss the current limitations of joint profiling technologies, prospects for future improvement, the extensibility of computational tools, and the potential for co-assaying with additional omics data.<\/jats:p>","DOI":"10.1093\/bib\/bbaf669","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T13:12:08Z","timestamp":1764162728000},"source":"Crossref","is-referenced-by-count":1,"title":["Assessment and applications of joint profiling of single-cell chromatin accessibility and transcriptome"],"prefix":"10.1093","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4104-3966","authenticated-orcid":false,"given":"Hongfei","family":"Li","sequence":"first","affiliation":[{"name":"Yangtze Delta Region Institute (Quzhou), University of Electronic Science and Technology of China , No. 1 Chengdian Road, Kecheng District, Quzhou 324003 ,","place":["China"]},{"name":"Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China , No. 2006, Xiyuan Ave, West Hi-Tech Zone, Chengdu 610054 ,","place":["China"]}]},{"given":"Jiechen","family":"Wang","sequence":"additional","affiliation":[{"name":"Yangtze Delta Region Institute (Quzhou), University of Electronic Science and Technology of China , No. 1 Chengdian Road, Kecheng District, Quzhou 324003 ,","place":["China"]},{"name":"Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China , No. 2006, Xiyuan Ave, West Hi-Tech Zone, Chengdu 610054 ,","place":["China"]}]},{"given":"Qing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Hospital (T.C.M) Affiliated to Southwest Medical University , No. 319, Section 3, Zhongshan Road, Luzhou 646099 ,","place":["China"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6406-1142","authenticated-orcid":false,"given":"Quan","family":"Zou","sequence":"additional","affiliation":[{"name":"Yangtze Delta Region Institute (Quzhou), University of Electronic Science and Technology of China , No. 1 Chengdian Road, Kecheng District, Quzhou 324003 ,","place":["China"]},{"name":"Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China , No. 2006, Xiyuan Ave, West Hi-Tech Zone, Chengdu 610054 ,","place":["China"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2956-6799","authenticated-orcid":false,"given":"Ximei","family":"Luo","sequence":"additional","affiliation":[{"name":"Yangtze Delta Region Institute (Quzhou), University of Electronic Science and Technology of China , No. 1 Chengdian Road, Kecheng District, Quzhou 324003 ,","place":["China"]},{"name":"Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China , No. 2006, Xiyuan Ave, West Hi-Tech Zone, Chengdu 610054 ,","place":["China"]}]}],"member":"286","published-online":{"date-parts":[[2025,12,12]]},"reference":[{"key":"2025121211334688800_ref1","doi-asserted-by":"publisher","first-page":"212106","DOI":"10.1007\/s11432-024-4171-9","article-title":"SBSM-pro: Support bio-sequence machine for proteins","volume":"67","author":"Wang","year":"2024","journal-title":"Sci China Inf Sci"},{"key":"2025121211334688800_ref2","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1038\/s41592-023-01842-x","article-title":"Single-cell measurement of dynamic protein secretion and transcriptome","volume":"20","author":"Cheow","year":"2023","journal-title":"Nat Methods"},{"key":"2025121211334688800_ref3","doi-asserted-by":"publisher","first-page":"200","DOI":"10.3390\/cells12010200","article-title":"A live cell protein complementation assay for ORFeome-wide probing of human HOX Interactomes","volume":"12","author":"Jia","year":"2023","journal-title":"Cells"},{"key":"2025121211334688800_ref4","doi-asserted-by":"publisher","first-page":"1662","DOI":"10.1101\/gr.278130.123","article-title":"Clustered and diverse transcription factor binding underlies cell type specificity of enhancers for housekeeping genes","volume":"33","author":"Zhu","year":"2023","journal-title":"Genome Res"},{"key":"2025121211334688800_ref5","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1186\/s12915-023-01590-6","article-title":"Promoter evolution of mammalian gene duplicates","volume":"21","author":"Fraimovitch","year":"2023","journal-title":"BMC Biol"},{"key":"2025121211334688800_ref6","doi-asserted-by":"publisher","first-page":"113259","DOI":"10.1016\/j.celrep.2023.113259","article-title":"CTCF coordinates cell fate specification via orchestrating regulatory hubs with pioneer transcription factors","volume":"42","author":"Liu","year":"2023","journal-title":"Cell Rep"},{"key":"2025121211334688800_ref7","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1186\/s12915-024-01989-9","article-title":"Genome binding properties of Zic transcription factors underlie their changing functions during neuronal maturation","volume":"22","author":"Minto","year":"2024","journal-title":"BMC Biol"},{"key":"2025121211334688800_ref8","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/j.cell.2022.11.026","article-title":"A transcription factor atlas of directed differentiation","volume":"186","author":"Joung","year":"2023","journal-title":"Cell"},{"key":"2025121211334688800_ref9","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1186\/s12964-024-01640-8","article-title":"Integrated proteomic, phosphoproteomic, and N\u2212glycoproteomic analyses of small extracellular vesicles from C2C12 myoblasts identify specific PTM patterns in ligand-receptor interactions","volume":"22","author":"Chen","year":"2024","journal-title":"Cell Commun Signal"},{"key":"2025121211334688800_ref10","doi-asserted-by":"publisher","first-page":"107309","DOI":"10.1016\/j.isci.2023.107309","article-title":"A ligand-receptor interactome atlas of the zebrafish","volume":"26","author":"Chodkowski","year":"2023","journal-title":"Iscience"},{"key":"2025121211334688800_ref11","doi-asserted-by":"publisher","first-page":"1455","DOI":"10.1093\/plcell\/koad032","article-title":"Signaling by the EPFL-ERECTA family coordinates female germline specification through the BZR1 family in Arabidopsis","volume":"35","author":"Cai","year":"2023","journal-title":"Plant Cell"},{"key":"2025121211334688800_ref12","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-39881-9","article-title":"Deciphering intercellular signaling complexes by interaction-guided chemical proteomics","volume":"14","author":"Zheng","year":"2023","journal-title":"Nat Commun"},{"key":"2025121211334688800_ref13","doi-asserted-by":"publisher","first-page":"3379","DOI":"10.3892\/ijmm.2018.3526","article-title":"MicroRNA-155 inhibits the osteogenic differentiation of mesenchymal stem cells induced by BMP9 via downregulation of BMP signaling pathway","volume":"41","author":"Liu","year":"2018","journal-title":"Int J Mol Med"},{"key":"2025121211334688800_ref14","doi-asserted-by":"publisher","first-page":"110120","DOI":"10.1016\/j.clim.2024.110120","article-title":"Case study: IgG deficient patient receiving immune globulin intravenous, human-slra 10% demonstrates improvement in quality of life","volume":"262","author":"Miller","year":"2024","journal-title":"Clin Immunol"},{"key":"2025121211334688800_ref15","doi-asserted-by":"publisher","first-page":"2445","DOI":"10.3201\/eid3011.241331","article-title":"Mpox hepatic and pulmonary lesions in HIV\/hepatitis B virus Co-infected patient, France","volume":"30","author":"Calin","year":"2024","journal-title":"Emerg Infect Dis"},{"key":"2025121211334688800_ref16","doi-asserted-by":"publisher","first-page":"2854","DOI":"10.3324\/haematol.2023.284632","article-title":"Anti-T-lymphocyte globulin exposure is associated with acute graft-versus\u2212host disease and relapse in pediatric acute lymphoblastic leukemia patients undergoing hematopoietic stem cell transplantation: A multinational prospective study","volume":"109","author":"Oostenbrink","year":"2024","journal-title":"Haematologica"},{"key":"2025121211334688800_ref17","doi-asserted-by":"publisher","first-page":"1010-+","DOI":"10.1126\/science.abd0827","article-title":"Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail","volume":"369","author":"Hansen","year":"2020","journal-title":"Science"},{"key":"2025121211334688800_ref18","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1186\/s12864-024-10218-0","article-title":"GNNMF: A multi-view graph neural network for ATAC-seq motif finding","volume":"25","author":"Zhang","year":"2024","journal-title":"BMC Genomics"},{"key":"2025121211334688800_ref19","doi-asserted-by":"publisher","first-page":"6852","DOI":"10.1038\/s41467-024-50680-8","article-title":"Quantitative analysis of cis-regulatory elements in transcription with KAS-ATAC-seq","volume":"15","author":"Lyu","year":"2024","journal-title":"Nat Commun"},{"key":"2025121211334688800_ref20","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1038\/s41587-021-01091-3","article-title":"Identifying phenotype-associated subpopulations by integrating bulk and single-cell sequencing data","volume":"40","author":"Sun","year":"2022","journal-title":"Nat Biotechnol"},{"key":"2025121211334688800_ref21","doi-asserted-by":"publisher","first-page":"bbab259","DOI":"10.1093\/bib\/bbab259","article-title":"Demystifying emerging bulk RNA-Seq applications: The application and utility of bioinformatic methodology","volume":"22","author":"Thind","year":"2021","journal-title":"Brief Bioinform"},{"key":"2025121211334688800_ref22","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1007\/s11883-022-01078-8","article-title":"From 'omics to multi-omics technologies: The discovery of novel causal mediators","volume":"25","author":"Mohammadi-Shemirani","year":"2023","journal-title":"Curr Atheroscler Rep"},{"key":"2025121211334688800_ref23","doi-asserted-by":"publisher","first-page":"e315","DOI":"10.1002\/mco2.315","article-title":"Applications of multi-omics analysis in human diseases","volume":"4","author":"Chen","year":"2023","journal-title":"MedComm"},{"key":"2025121211334688800_ref24","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2024.10.004","article-title":"AlphaFold2 enables accurate deorphanization of ligands to single-pass receptors","volume":"15","author":"Danneskiold-Samsoe","year":"2024","journal-title":"Cell Syst"},{"key":"2025121211334688800_ref25","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1186\/s13059-024-03246-2","article-title":"Single cell atlas: A single-cell multi-omics human cell encyclopedia","volume":"25","author":"Pan","year":"2024","journal-title":"Genome Biol"},{"key":"2025121211334688800_ref26","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1186\/s13059-023-03123-4","article-title":"Challenges and opportunities to computationally deconvolve heterogeneous tissue with varying cell sizes using single-cell RNA-sequencing datasets","volume":"24","author":"Maden","year":"2023","journal-title":"Genome Biol"},{"key":"2025121211334688800_ref27","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1186\/s13059-023-03025-5","article-title":"LAST-seq: Single-cell RNA sequencing by direct amplification of single-stranded RNA without prior reverse transcription and second-strand synthesis","volume":"24","author":"Lyu","year":"2023","journal-title":"Genome Biol"},{"key":"2025121211334688800_ref28","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1038\/s41587-024-02161-y","article-title":"Prediction of tumor-reactive T cell receptors from scRNA-seq data for personalized T cell therapy","volume":"43","author":"Tan","year":"2025","journal-title":"Nat Biotechnol"},{"key":"2025121211334688800_ref29","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-023-02112-6","article-title":"Modeling fragment counts improves single-cell ATAC-seq analysis","volume":"21","author":"Martens","year":"2024","journal-title":"Nat Methods"},{"key":"2025121211334688800_ref30","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-024-02256-6","article-title":"Decoding cell replicational age from single-cell ATAC-seq data","author":"Xiao","journal-title":"Nat Biotechnol"},{"key":"2025121211334688800_ref31","doi-asserted-by":"publisher","first-page":"1128","DOI":"10.1038\/s42003-024-06790-6","article-title":"starTracer is an accelerated approach for precise marker gene identification in single-cell RNA-Seq analysis","volume":"7","author":"Zhang","year":"2024","journal-title":"Commun Biol"},{"key":"2025121211334688800_ref32","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1186\/s40364-023-00523-3","article-title":"singleCellBase: A high-quality manually curated database of cell markers for single cell annotation across multiple species","volume":"11","author":"Meng","year":"2023","journal-title":"Biomark Res"},{"key":"2025121211334688800_ref33","doi-asserted-by":"publisher","first-page":"100641","DOI":"10.1016\/j.xgen.2024.100641","article-title":"An isoform-resolution transcriptomic atlas of colorectal cancer from long-read single-cell sequencing","volume":"4","author":"Li","year":"2024","journal-title":"Cell Genom"},{"key":"2025121211334688800_ref34","doi-asserted-by":"publisher","first-page":"e2405543","DOI":"10.1002\/advs.202405543","article-title":"Single-cell RNA sequencing uncovers pathological processes and crucial targets for vascular endothelial injury in diabetic hearts","volume":"11","author":"Zhang","year":"2024","journal-title":"Adv Sci (Weinh)"},{"key":"2025121211334688800_ref35","doi-asserted-by":"publisher","first-page":"eadk9217","DOI":"10.1126\/science.adk9217","article-title":"Single-cell chromatin accessibility reveals malignant regulatory programs in primary human cancers","volume":"385","author":"Sundaram","year":"2024","journal-title":"Science"},{"key":"2025121211334688800_ref36","doi-asserted-by":"publisher","first-page":"6742","DOI":"10.1016\/j.cell.2024.09.047","article-title":"A multimodal zebrafish developmental atlas reveals the state-transition dynamics of late-vertebrate pluripotent axial progenitors","volume":"187","author":"Lange","year":"2024","journal-title":"Cell"},{"key":"2025121211334688800_ref37","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1038\/s41586-024-08189-z","article-title":"A multi-omic atlas of human embryonic skeletal development","volume":"635","author":"To, K","year":"2024","journal-title":"Nature"},{"key":"2025121211334688800_ref38","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1038\/s41580-024-00768-2","article-title":"Profiling cell identity and tissue architecture with single-cell and spatial transcriptomics","volume":"26","author":"Gulati","year":"2025","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2025121211334688800_ref39","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1038\/s41580-023-00615-w","article-title":"The technological landscape and applications of single-cell multi-omics","volume":"24","author":"Baysoy","year":"2023","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2025121211334688800_ref40","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1038\/s41590-024-02059-6","article-title":"Integrating single-cell RNA and T\u2009cell\/B\u2009cell receptor sequencing with mass cytometry reveals dynamic trajectories of human peripheral immune cells from birth to old age","volume":"26","author":"Wang","year":"2025","journal-title":"Nat Immunol"},{"key":"2025121211334688800_ref41","doi-asserted-by":"publisher","first-page":"e2409642","DOI":"10.1002\/advs.202409642","article-title":"Dynamics of cell fate decisions during chemically induced multi-lineage trans-differentiation at single-cell level","volume":"12","author":"E","year":"2025","journal-title":"Adv Sci (Weinh)"},{"key":"2025121211334688800_ref42","doi-asserted-by":"publisher","first-page":"e3002770","DOI":"10.1371\/journal.pbio.3002770","article-title":"bHLH transcription factors cooperate with chromatin remodelers to regulate cell fate decisions during Arabidopsis stomatal development","volume":"22","author":"Liu","year":"2024","journal-title":"PLoS Biol"},{"key":"2025121211334688800_ref43","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1038\/s41586-024-08008-5","article-title":"Targeting immune-fibroblast cell communication in heart failure","volume":"635","author":"Amrute","year":"2024","journal-title":"Nature"},{"key":"2025121211334688800_ref44","doi-asserted-by":"publisher","first-page":"110662","DOI":"10.1016\/j.compbiomed.2025.110662","article-title":"Single-cell multi-omics analysis reveals the plasticity of isthmus stem cells in gastric carcinogenesis","volume":"195","author":"Liu","year":"2025","journal-title":"Comput Biol Med"},{"key":"2025121211334688800_ref45","doi-asserted-by":"publisher","DOI":"10.1126\/science.aba7721","article-title":"A human cell atlas of fetal gene expression","volume":"370","author":"Cao","year":"2020","journal-title":"Science"},{"key":"2025121211334688800_ref46","doi-asserted-by":"publisher","DOI":"10.1126\/science.aba7612","article-title":"A human cell atlas of fetal chromatin accessibility","volume":"370","author":"Domcke","year":"2020","journal-title":"Science"},{"key":"2025121211334688800_ref47","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1038\/s41586-022-04518-2","article-title":"A single-cell atlas of human and mouse white adipose tissue","volume":"603","author":"Emont","year":"2022","journal-title":"Nature"},{"key":"2025121211334688800_ref48","doi-asserted-by":"publisher","first-page":"1925","DOI":"10.1038\/s41588-024-01873-w","article-title":"An integrated single-cell reference atlas of the human endometrium","volume":"56","author":"Mare\u010dkov\u00e1","year":"2024","journal-title":"Nat Genet"},{"key":"2025121211334688800_ref49","doi-asserted-by":"publisher","first-page":"1380","DOI":"10.1126\/science.aau0730","article-title":"Joint profiling of chromatin accessibility and gene expression in thousands of single cells","volume":"361","author":"Cao","year":"2018","journal-title":"Science"},{"key":"2025121211334688800_ref50","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1038\/s41467-018-08205-7","article-title":"Deconvolution of single-cell multi-omics layers reveals regulatory heterogeneity","volume":"10","author":"Liu","year":"2019","journal-title":"Nat Commun"},{"key":"2025121211334688800_ref51","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1038\/nmeth.2639","article-title":"Smart-seq2 for sensitive full-length transcriptome profiling in single cells","volume":"10","author":"Picelli","year":"2013","journal-title":"Nat Methods"},{"key":"2025121211334688800_ref52","doi-asserted-by":"publisher","first-page":"1452","DOI":"10.1038\/s41587-019-0290-0","article-title":"High-throughput sequencing of the transcriptome and chromatin accessibility in the same cell","volume":"37","author":"Chen","year":"2019","journal-title":"Nat Biotechnol"},{"key":"2025121211334688800_ref53","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1038\/s41594-019-0323-x","article-title":"An ultra high-throughput method for single-cell joint analysis of open chromatin and transcriptome","volume":"26","author":"Zhu","year":"2019","journal-title":"Nat Struct Mol Biol"},{"key":"2025121211334688800_ref54","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1126\/science.aam8999","article-title":"Single-cell profiling of the developing mouse brain and spinal cord with split-pool barcoding","volume":"360","author":"Rosenberg","year":"2018","journal-title":"Science"},{"key":"2025121211334688800_ref55","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1016\/j.cell.2020.09.056","article-title":"Chromatin potential identified by shared single-cell profiling of RNA and chromatin","volume":"183","author":"Ma","year":"2020","journal-title":"Cell"},{"key":"2025121211334688800_ref56","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1038\/s41592-022-01601-4","article-title":"ISSAAC-seq enables sensitive and flexible multimodal profiling of chromatin accessibility and gene expression in single cells","volume":"19","author":"Xu","year":"2022","journal-title":"Nat Methods"},{"key":"2025121211334688800_ref57","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1038\/s41592-021-01282-5","article-title":"Single-cell chromatin state analysis with Signac","volume":"18","author":"Stuart","year":"2021","journal-title":"Nat Methods"},{"key":"2025121211334688800_ref58","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbae649","article-title":"GSTRPCA: Irregular tensor singular value decomposition for single-cell multi-omics data clustering","volume":"26","author":"Cui","year":"2024","journal-title":"Brief Bioinform"},{"key":"2025121211334688800_ref59","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1186\/s12915-025-02177-z","article-title":"AnomalGRN: Deciphering single-cell gene regulation network with graph anomaly detection","volume":"23","author":"Zhou","year":"2025","journal-title":"BMC Biol"},{"key":"2025121211334688800_ref60","doi-asserted-by":"publisher","first-page":"9005","DOI":"10.1109\/tnnls.2024.3412753","article-title":"GRACE: Unveiling gene regulatory networks with causal mechanistic graph neural networks in single-cell RNA-sequencing data","volume":"36","author":"Wang","year":"2025","journal-title":"IEEE Trans Neural Netw Learn Syst"},{"key":"2025121211334688800_ref61","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1186\/s13059-015-0844-5","article-title":"MAST: A flexible statistical framework for assessing transcriptional changes and characterizing heterogeneity in single-cell RNA sequencing data","volume":"16","author":"Finak","year":"2015","journal-title":"Genome Biol"},{"key":"2025121211334688800_ref62","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s13059-017-1382-0","article-title":"SCANPY: Large-scale single-cell gene expression data analysis","volume":"19","author":"Wolf","year":"2018","journal-title":"Genome Biol"},{"key":"2025121211334688800_ref63","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1038\/s41587-023-01767-y","article-title":"Dictionary learning for integrative, multimodal and scalable single-cell analysis","volume":"42","author":"Hao","year":"2024","journal-title":"Nat Biotechnol"},{"key":"2025121211334688800_ref64","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1038\/s41596-024-01045-4","article-title":"CellChat for systematic analysis of cell-cell communication from single-cell transcriptomics","volume":"20","author":"Jin","year":"2025","journal-title":"Nat Protoc"},{"key":"2025121211334688800_ref65","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0591-3","article-title":"Generalizing RNA velocity to transient cell states through dynamical modeling","volume":"38","author":"Bergen","year":"2020","journal-title":"Nat Biotechnol"},{"key":"2025121211334688800_ref66","doi-asserted-by":"publisher","first-page":"979-+","DOI":"10.1038\/nmeth.4402","article-title":"Reversed graph embedding resolves complex single-cell trajectories","volume":"14","author":"Qiu","year":"2017","journal-title":"Nat Methods"},{"key":"2025121211334688800_ref67","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-024-01137-1","article-title":"CellPhoneDB v5: Inferring cell-cell communication from single-cell multiomics data","author":"Troul\u00e9","journal-title":"Nat Protoc"},{"key":"2025121211334688800_ref68","doi-asserted-by":"publisher","first-page":"1337","DOI":"10.1038\/s41467-021-21583-9","article-title":"Comprehensive analysis of single cell ATAC-seq data with SnapATAC","volume":"12","author":"Fang","year":"2021","journal-title":"Nat Commun"},{"key":"2025121211334688800_ref69","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1186\/s13059-020-02008-0","article-title":"scATAC-pro: A comprehensive workbench for single-cell chromatin accessibility sequencing data","volume":"21","author":"Yu","year":"2020","journal-title":"Genome Biol"},{"key":"2025121211334688800_ref70","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1016\/j.molcel.2018.06.044","article-title":"Cicero predicts cis-regulatory DNA interactions from single-cell chromatin accessibility data","volume":"71","author":"Pliner","year":"2018","journal-title":"Mol Cell"},{"key":"2025121211334688800_ref71","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1038\/nmeth.4401","article-title":"chromVAR: Inferring transcription-factor-associated accessibility from single-cell epigenomic data","volume":"14","author":"Schep","year":"2017","journal-title":"Nat Methods"},{"key":"2025121211334688800_ref72","doi-asserted-by":"publisher","first-page":"4267","DOI":"10.1038\/s41467-020-18035-1","article-title":"ATAC-seq footprinting unravels kinetics of transcription factor binding during zygotic genome activation","volume":"11","author":"Bentsen","year":"2020","journal-title":"Nat Commun"},{"key":"2025121211334688800_ref73","doi-asserted-by":"publisher","first-page":"403-+","DOI":"10.1038\/s41588-021-00790-6","article-title":"ArchR is a scalable software package for integrative single-cell chromatin accessibility analysis","volume":"53","author":"Granja","year":"2021","journal-title":"Nat Genet"},{"key":"2025121211334688800_ref74","doi-asserted-by":"publisher","first-page":"1355","DOI":"10.1038\/s41592-023-01938-4","article-title":"SCENIC+: Single-cell multiomic inference of enhancers and gene regulatory networks","volume":"20","author":"Bravo Gonz\u00e1lez-Blas","year":"2023","journal-title":"Nat Methods"},{"key":"2025121211334688800_ref75","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1038\/s41592-019-0367-1","article-title":"cisTopic: Cis-regulatory topic modeling on single-cell ATAC-seq data","volume":"16","author":"Bravo Gonz\u00e1lez-Blas","year":"2019","journal-title":"Nat Methods"},{"key":"2025121211334688800_ref76","doi-asserted-by":"publisher","first-page":"102696","DOI":"10.1016\/j.omtn.2025.102696","article-title":"Single-cell multi-omics data reveal heterogeneity in liver tissue microenvironment induced by hypertension","volume":"36","author":"Li","year":"2025","journal-title":"Mol Ther Nucleic Acids"},{"key":"2025121211334688800_ref77","doi-asserted-by":"publisher","first-page":"e2308384","DOI":"10.1002\/advs.202308384","article-title":"Multiome in the same cell reveals the impact of osmotic stress on Arabidopsis root tip development at single-cell level","volume":"11","author":"Liu","year":"2024","journal-title":"Adv Sci (Weinh)"},{"key":"2025121211334688800_ref78","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1038\/s41592-020-01041-y","article-title":"High-accuracy long-read amplicon sequences using unique molecular identifiers with Nanopore or PacBio sequencing","volume":"18","author":"Karst","year":"2021","journal-title":"Nat Methods"},{"key":"2025121211334688800_ref79","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1038\/s41576-025-00828-z","article-title":"Transcriptomics in the era of long-read sequencing","volume":"26","author":"Monz\u00f3","year":"2025","journal-title":"Nat Rev Genet"},{"key":"2025121211334688800_ref80","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbae095","article-title":"Benchmarking multi-omics integration algorithms across single-cell RNA and ATAC data","volume":"25","author":"Xiao","year":"2024","journal-title":"Brief Bioinform"},{"key":"2025121211334688800_ref81","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1038\/s41467-021-20950-w","article-title":"An all-to-all approach to the identification of sequence-specific readers for epigenetic DNA modifications on cytosine","volume":"12","author":"Song","year":"2021","journal-title":"Nat Commun"}],"container-title":["Briefings in Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bib\/article-pdf\/26\/6\/bbaf669\/65855748\/bbaf669.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bib\/article-pdf\/26\/6\/bbaf669\/65855748\/bbaf669.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T16:33:55Z","timestamp":1765557235000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bib\/article\/doi\/10.1093\/bib\/bbaf669\/8378205"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,1]]},"references-count":81,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,11,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bib\/bbaf669","relation":{},"ISSN":["1467-5463","1477-4054"],"issn-type":[{"value":"1467-5463","type":"print"},{"value":"1477-4054","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,11]]},"published":{"date-parts":[[2025,11,1]]},"article-number":"bbaf669"}}