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
2025
Thatchayut Unjitwattana | Qianhui Huang | Yiwen Yang | Leyang Tao | Youqi Yang | Mengtian Zhou | Yuheng Du | Lana X. Garmire
Abstract Single-cell RNA sequencing (scRNA-seq) data from complex human tissues have prevalent blood cell contamination during the sample preparation process. 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.
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