Extracellular vesicles (EVs) are complex ecosystems that can be derived from all body cells and circulated in the body fluids. Characterizing the tissue-cellular source contributing to circulating EVs provides biological information about the cell or tissue of origin and their functional states. However, the relative proportion of tissue-cellular origin of circulating EVs in body fluid has not been thoroughly characterized. Here, we developed an approach for digital EVs quantification, called EV-origin, that enables enumerating of EVs tissue-cellular source contribution from plasma extracellular vesicles long RNA sequencing profiles. EV-origin was constructed by the input matrix of gene expression signatures and robust deconvolution algorithm, collectively used to separate the relative proportions of each tissue or cell type of interest. EV-origin respectively predicted the relative enrichment of seven types of hemopoietic cells and sixteen solid tissue subsets from exLR-seq profile. Using the EV-origin approach, we depicted an integrated landscape of the traceability system of plasma EVs for healthy individuals. We also compared the heterogenous tissue-cellular source components from plasma EVs samples with diverse disease status. Notably, the aberrant liver fraction could reflect the development and progression of hepatic disease. The liver fraction could also serve as a diagnostic indicator and effectively separate HCC patients from normal individuals. The EV-origin provides an approach to decipher the complex heterogeneity of tissue-cellular origin in circulating EVs. Our approach could inform the development of exLR-based applications for liquid biopsy.

细胞外囊泡（EVs）是复杂的生态系统，可以衍生自所有体细胞并在体液中循环。表征有助于循环电动汽车的组织细胞来源可提供有关起源细胞或组织及其功能状态的生物学信息。但是，尚未充分表征循环电动汽车在组织液中的组织细胞起源的相对比例。在这里，我们开发了一种称为EV起源的数字EV量化方法，该方法可以枚举来自血浆细胞外小泡长RNA测序图谱的EV组织细胞来源。EV起源是由基因表达特征的输入矩阵和鲁棒的反卷积算法构成的，共同用于分离感兴趣的每种组织或细胞类型的相对比例。EV起源分别从exLR-seq图谱预测了七种造血细胞和十六种实体组织亚群的相对富集。使用电动车起源方法，我们描绘了健康个体血浆电动车可追溯系统的综合图景。我们还比较了血浆EV样品中具有多种疾病状态的异质组织细胞源成分。值得注意的是，异常肝脏分数可能反映了肝病的发生和发展。肝部分也可以作为诊断指标，有效地将HCC患者与正常人区分开。电动汽车的起源提供了一种方法，可用于解释循环电动汽车中组织细胞起源的复杂异质性。我们的方法可能有助于开发基于exLR的液体活检应用。