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They may also comprise cells of different genetic makeups. We propose a new computational framework, Originator, which deciphers single cells by genetic origin and separates immune cells of blood contamination from those of expected tissue-resident cells. We demonstrate the accuracy of Originator at separating immune cells from the blood and tissue as well as cells of different genetic origins, using a variety of artificially mixed and real datasets, including pancreatic cancer and placentas as examples.<\/jats:p>","DOI":"10.1186\/s13059-025-03495-9","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T07:37:47Z","timestamp":1741678667000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Single-cell RNA-seq data have prevalent blood contamination but can be rescued by Originator, a computational tool separating single-cell RNA-seq by genetic and contextual information"],"prefix":"10.1186","volume":"26","author":[{"given":"Thatchayut","family":"Unjitwattana","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qianhui","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiwen","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leyang","family":"Tao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youqi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengtian","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuheng","family":"Du","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lana X.","family":"Garmire","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,3,11]]},"reference":[{"key":"3495_CR1","doi-asserted-by":"crossref","unstructured":"Del Prete A, Wu Q. 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