Comprehensive evaluation of methods for identifying tissues or cell types of origin of the plasma cell-free transcriptome

Plasma cell-free RNA (cfRNA) is derived from cells in various tissues and organs throughout the body and reflects the physiological and pathological conditions. Identifying the origins of cfRNA is essential for comprehending its variations. Only a few tools are designed for cfRNA deconvolution, and...

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Main Authors: Tingyu Yang, Yulong Qin, Shuo Yan, Sijia Guo, Jinghua Sun, Jiayi Huang, Jiayi Li, Qing Zhou, Xin Jin, Wen-Jing Wang
Format: Article
Language:English
Published: PeerJ Inc. 2025-04-01
Series:PeerJ
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Online Access:https://peerj.com/articles/19241.pdf
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author Tingyu Yang
Yulong Qin
Shuo Yan
Sijia Guo
Jinghua Sun
Jiayi Huang
Jiayi Li
Qing Zhou
Xin Jin
Wen-Jing Wang
author_facet Tingyu Yang
Yulong Qin
Shuo Yan
Sijia Guo
Jinghua Sun
Jiayi Huang
Jiayi Li
Qing Zhou
Xin Jin
Wen-Jing Wang
author_sort Tingyu Yang
collection DOAJ
description Plasma cell-free RNA (cfRNA) is derived from cells in various tissues and organs throughout the body and reflects the physiological and pathological conditions. Identifying the origins of cfRNA is essential for comprehending its variations. Only a few tools are designed for cfRNA deconvolution, and most studies have relied on traditional bulk RNA methods. In this study, we employed human tissue and cell transcriptomic data as reference sets and evaluated the performance of seven deconvolution methods on cfRNA. We compared the analysis results of cell types and tissues of origin of plasma cfRNA and chose to use single-cell RNA sequencing (scRNA-seq) data as reference to conduct further evaluation of deconvolution methods. Subsequently, we assessed the accuracy and robustness of the methods by utilizing simulated cfRNA data generated from scRNA-seq. We also evaluated the methods’ accuracy on real plasma cfRNA data by analyzing the correlation between the predicted cell proportions and the corresponding clinical indicators. Moreover, we compared the methods’ effectiveness in revealing the impacts of diseases on cells and evaluated the performance of cancer classification models based on the cell origin data they provided. In summary, our study provides valuable insights into cfRNA origin analysis, enhancing its potential in biomedical research.
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spelling doaj-art-b4a9b1e59a99425cb206cefd15446a892025-08-20T03:18:15ZengPeerJ Inc.PeerJ2167-83592025-04-0113e1924110.7717/peerj.19241Comprehensive evaluation of methods for identifying tissues or cell types of origin of the plasma cell-free transcriptomeTingyu Yang0Yulong Qin1Shuo Yan2Sijia Guo3Jinghua Sun4Jiayi Huang5Jiayi Li6Qing Zhou7Xin Jin8Wen-Jing Wang9College of Life Sciences, University of Chinese Academy of Sciences, Beijing, ChinaCollege of Life Sciences, University of Chinese Academy of Sciences, Beijing, ChinaCollege of Life Sciences, University of Chinese Academy of Sciences, Beijing, ChinaBGI Research, Shenzhen, ChinaBGI Research, Shenzhen, ChinaBGI Research, Shenzhen, ChinaCollege of Life Sciences, University of Chinese Academy of Sciences, Beijing, ChinaBGI Research, Shenzhen, ChinaCollege of Life Sciences, University of Chinese Academy of Sciences, Beijing, ChinaBGI Research, Shenzhen, ChinaPlasma cell-free RNA (cfRNA) is derived from cells in various tissues and organs throughout the body and reflects the physiological and pathological conditions. Identifying the origins of cfRNA is essential for comprehending its variations. Only a few tools are designed for cfRNA deconvolution, and most studies have relied on traditional bulk RNA methods. In this study, we employed human tissue and cell transcriptomic data as reference sets and evaluated the performance of seven deconvolution methods on cfRNA. We compared the analysis results of cell types and tissues of origin of plasma cfRNA and chose to use single-cell RNA sequencing (scRNA-seq) data as reference to conduct further evaluation of deconvolution methods. Subsequently, we assessed the accuracy and robustness of the methods by utilizing simulated cfRNA data generated from scRNA-seq. We also evaluated the methods’ accuracy on real plasma cfRNA data by analyzing the correlation between the predicted cell proportions and the corresponding clinical indicators. Moreover, we compared the methods’ effectiveness in revealing the impacts of diseases on cells and evaluated the performance of cancer classification models based on the cell origin data they provided. In summary, our study provides valuable insights into cfRNA origin analysis, enhancing its potential in biomedical research.https://peerj.com/articles/19241.pdfPlasma cfRNACell originsTissue originsCancer classification
spellingShingle Tingyu Yang
Yulong Qin
Shuo Yan
Sijia Guo
Jinghua Sun
Jiayi Huang
Jiayi Li
Qing Zhou
Xin Jin
Wen-Jing Wang
Comprehensive evaluation of methods for identifying tissues or cell types of origin of the plasma cell-free transcriptome
PeerJ
Plasma cfRNA
Cell origins
Tissue origins
Cancer classification
title Comprehensive evaluation of methods for identifying tissues or cell types of origin of the plasma cell-free transcriptome
title_full Comprehensive evaluation of methods for identifying tissues or cell types of origin of the plasma cell-free transcriptome
title_fullStr Comprehensive evaluation of methods for identifying tissues or cell types of origin of the plasma cell-free transcriptome
title_full_unstemmed Comprehensive evaluation of methods for identifying tissues or cell types of origin of the plasma cell-free transcriptome
title_short Comprehensive evaluation of methods for identifying tissues or cell types of origin of the plasma cell-free transcriptome
title_sort comprehensive evaluation of methods for identifying tissues or cell types of origin of the plasma cell free transcriptome
topic Plasma cfRNA
Cell origins
Tissue origins
Cancer classification
url https://peerj.com/articles/19241.pdf
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