{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T01:13:28Z","timestamp":1776561208964,"version":"3.51.2"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T00:00:00Z","timestamp":1634256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/summer-heart-0930.chufeiyun1688.workers.dev:443\/https\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100000015","name":"Canadian Cancer Society Research Institute","doi-asserted-by":"publisher","award":["702987"],"award-info":[{"award-number":["702987"]}],"id":[{"id":"10.13039\/501100000015","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,1,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chromosome copy number variations (CNVs) are a near-universal feature of cancer; however, their individual effects on cellular function are often incompletely understood. Single-cell ribonucleic acid (RNA) sequencing (scRNA-seq) might be leveraged to reveal the function of intra-clonal CNVs; however, it cannot directly link cellular gene expression to CNVs. Here, we report a high-throughput scRNA-seq analysis pipeline that provides paired CNV profiles and transcriptomes for single cells, enabling exploration of the effects of CNVs on cellular programs. RTAM1 and\u00a0-2 normalization methods are described, and are shown to improve transcriptome alignment between cells, increasing the sensitivity of scRNA-seq for CNV detection. We also report single-cell inferred chromosomal copy number variation (sciCNV), a tool for inferring single-cell CNVs from scRNA-seq at 19\u201346\u00a0Mb resolution. Comparison of sciCNV with existing RNA-based CNV methods reveals useful advances in sensitivity and specificity. Using sciCNV, we demonstrate that scRNA-seq can be used to examine the cellular effects of cancer CNVs. As an example, sciCNV is used to identify subclonal multiple myeloma (MM) cells with +8q22\u201324. Studies of the gene expression of intra-clonal MM cells with and without the CNV demonstrate that +8q22\u201324 upregulates MYC and MYC-target genes, messenger RNA processing and protein synthesis, which is consistent with established models. In conclusion, we provide new tools for scRNA-seq that enable paired profiling of the CNVs and transcriptomes of single cells, facilitating rapid and accurate deconstruction of the effects of cancer CNVs on cellular programming.<\/jats:p>","DOI":"10.1093\/bib\/bbab413","type":"journal-article","created":{"date-parts":[[2021,9,9]],"date-time":"2021-09-09T23:09:08Z","timestamp":1631228948000},"source":"Crossref","is-referenced-by-count":24,"title":["sciCNV: high-throughput paired profiling of transcriptomes and DNA copy number variations at single-cell resolution"],"prefix":"10.1093","volume":"23","author":[{"ORCID":"https:\/\/summer-heart-0930.chufeiyun1688.workers.dev:443\/https\/orcid.org\/0000-0002-4201-2937","authenticated-orcid":false,"given":"Ali","family":"Mahdipour-Shirayeh","sequence":"first","affiliation":[{"name":"Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada"}]},{"given":"Natalie","family":"Erdmann","sequence":"additional","affiliation":[{"name":"Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada"}]},{"given":"Chungyee","family":"Leung-Hagesteijn","sequence":"additional","affiliation":[{"name":"Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada"}]},{"given":"Rodger E","family":"Tiedemann","sequence":"additional","affiliation":[{"name":"Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada"},{"name":"Department of Medicine, University of Toronto, Toronto, Ontario, Canada"}]}],"member":"286","published-online":{"date-parts":[[2021,10,15]]},"reference":[{"key":"2022011921124352300_ref1","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1038\/nature08822","article-title":"The landscape of somatic copy-number alteration across human 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