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scCDC: a computational method for gene-specific contamination detection and correction in single-cell and single-nucleus RNA-seq data

Weijian Wang, Yihui Cen, Zezhen Lu, Yueqing Xu, Tianyi Sun, Ying Xiao, Wanlu Liu, View ORCID ProfileJingyi Jessica Li, View ORCID ProfileChaochen Wang
doi: https://doi.org/10.1101/2022.11.24.517598
Weijian Wang
1ZJU-UoE Institute, Zhejiang University School of Medicine, International Campus, Zhejiang University, Haining, 314400, Zhejiang, China
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Yihui Cen
1ZJU-UoE Institute, Zhejiang University School of Medicine, International Campus, Zhejiang University, Haining, 314400, Zhejiang, China
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Zezhen Lu
1ZJU-UoE Institute, Zhejiang University School of Medicine, International Campus, Zhejiang University, Haining, 314400, Zhejiang, China
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Yueqing Xu
1ZJU-UoE Institute, Zhejiang University School of Medicine, International Campus, Zhejiang University, Haining, 314400, Zhejiang, China
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Tianyi Sun
3Department of Statistics, University of California, Los Angeles, CA, 90095, USA
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Ying Xiao
2Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310020, Zhejiang, China
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Wanlu Liu
1ZJU-UoE Institute, Zhejiang University School of Medicine, International Campus, Zhejiang University, Haining, 314400, Zhejiang, China
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Jingyi Jessica Li
3Department of Statistics, University of California, Los Angeles, CA, 90095, USA
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  • ORCID record for Jingyi Jessica Li
  • For correspondence: lijy03@g.ucla.edu chaochenwang@intl.zju.edu.cn
Chaochen Wang
1ZJU-UoE Institute, Zhejiang University School of Medicine, International Campus, Zhejiang University, Haining, 314400, Zhejiang, China
4Department of Breast Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310020, Zhejiang, China
5Biomedical and Health Translational Research Centre, Zhejiang University, 314400, Zhejiang, China
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  • ORCID record for Chaochen Wang
  • For correspondence: lijy03@g.ucla.edu chaochenwang@intl.zju.edu.cn
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Abstract

In droplet-based single-cell RNA-seq (scRNA-seq) and single-nucleus RNA-seq (snRNA-seq) assays, systematic contamination of ambient RNA molecules biases the estimation of genuine transcriptional levels. To correct the contamination, several computational methods have been developed. However, these methods do not distinguish the contamination-causing genes and thus either under- or over-corrected the contamination in our in-house snRNA-seq data of virgin and lactating mammary glands. Hence, we developed scCDC as the first method that specifically detects the contamination-causing genes and only corrects the expression counts of these genes. Benchmarked against existing methods on synthetic and real scRNA-seq and snRNA-seq datasets, scCDC achieved the best contamination correction accuracy with minimal data alteration. Moreover, scCDC applies to processed scRNA-seq and snRNA-seq data with empty droplets removed. In conclusion, scCDC is a flexible, accurate decontamination method that detects the contamination-causing genes, corrects the contamination, and avoids the over-correction of other genes.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted November 25, 2022.
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scCDC: a computational method for gene-specific contamination detection and correction in single-cell and single-nucleus RNA-seq data
Weijian Wang, Yihui Cen, Zezhen Lu, Yueqing Xu, Tianyi Sun, Ying Xiao, Wanlu Liu, Jingyi Jessica Li, Chaochen Wang
bioRxiv 2022.11.24.517598; doi: https://doi.org/10.1101/2022.11.24.517598
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scCDC: a computational method for gene-specific contamination detection and correction in single-cell and single-nucleus RNA-seq data
Weijian Wang, Yihui Cen, Zezhen Lu, Yueqing Xu, Tianyi Sun, Ying Xiao, Wanlu Liu, Jingyi Jessica Li, Chaochen Wang
bioRxiv 2022.11.24.517598; doi: https://doi.org/10.1101/2022.11.24.517598

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