{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:38:33Z","timestamp":1772138313749,"version":"3.50.1"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T00:00:00Z","timestamp":1728950400000},"content-version":"vor","delay-in-days":14,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Multiplexing across donors has emerged as a popular strategy to increase throughput, reduce costs, overcome technical batch effects, and improve doublet detection in single-cell genomic studies. To eliminate additional experimental steps, endogenous nuclear genome variants are used for demultiplexing pooled single-cell RNA sequencing (scRNA-seq) data by several computational tools. However, these tools have limitations when applied to single-cell sequencing methods that do not cover nuclear genomic regions well, such as single-cell assay for transposase-accessible chromatin with sequencing (scATAC-seq). Here, we demonstrate that mitochondrial germline variants are an alternative, robust, and computationally efficient endogenous barcode for sample demultiplexing. We propose MitoSort, a tool that uses mitochondrial germline variants to assign cells to their donor origins\u00a0and identify cross-genotype doublets in single-cell genomic datasets. We evaluate its performance by using in silico pooled mitochondrial scATAC-seq (mtscATAC-seq) libraries and experimentally multiplexed data with cell hashtags. MitoSort achieves high accuracy and efficiency in genotype clustering and doublet detection for mtscATAC-seq data, addressing the limitations of current computational techniques tailored for scRNA-seq data. Moreover, MitoSort exhibits versatility, and can be applied to various single-cell sequencing approaches beyond mtscATAC-seq provided that the mitochondrial variants are reliably detected. Furthermore, we demonstrate the application of MitoSort in a case study where B cells from eight donors were pooled and assayed by single-cell multi-omics sequencing. Altogether, our results demonstrate the accuracy and efficiency of MitoSort, which enables reliable sample demultiplexing in various single-cell genomic applications. MitoSort is available at https:\/\/github.com\/tangzhj\/MitoSort.<\/jats:p>","DOI":"10.1093\/gpbjnl\/qzae073","type":"journal-article","created":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T12:40:11Z","timestamp":1728996011000},"source":"Crossref","is-referenced-by-count":3,"title":["MitoSort: Robust Demultiplexing of Pooled Single-cell Genomic Data Using Endogenous Mitochondrial Variants"],"prefix":"10.1093","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3926-0717","authenticated-orcid":false,"given":"Zhongjie","family":"Tang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University , Guangzhou 510275,","place":["China"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0779-5948","authenticated-orcid":false,"given":"Weixing","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University , Guangzhou 510275,","place":["China"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4640-0830","authenticated-orcid":false,"given":"Peiyu","family":"Shi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University , Guangzhou 510275,","place":["China"]}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1426-4375","authenticated-orcid":false,"given":"Sijun","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University , Guangzhou 510275,","place":["China"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1837-4249","authenticated-orcid":false,"given":"Xinhui","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University , Guangzhou 510275,","place":["China"]}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4958-3337","authenticated-orcid":false,"given":"Yueming","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University , Guangzhou 510275,","place":["China"]}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5772-1842","authenticated-orcid":false,"given":"Yicong","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University , Guangzhou 510275,","place":["China"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2768-1654","authenticated-orcid":false,"given":"Yaqing","family":"Shu","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University , Guangzhou 510630,","place":["China"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1552-0060","authenticated-orcid":false,"given":"Zheng","family":"Hu","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences , Shenzhen 518055,","place":["China"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0944-9835","authenticated-orcid":false,"given":"Jin","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University , Guangzhou 510275,","place":["China"]}]}],"member":"286","published-online":{"date-parts":[[2024,10,15]]},"reference":[{"key":"2024122622063154800_qzae073-B1","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1038\/s41576-023-00580-2","article-title":"Methods and applications for single-cell and spatial 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