Brief Bioinform. 2021 May 20;22(3). doi: 10.1093/bib/bbaa060.
Advances in sequencing technologies facilitate personalized disease-risk profiling and clinical diagnosis. In recent years, some great progress has been made in noninvasive diagnoses based on cell-free DNAs (cfDNAs). It exploits the fact that dead cells release DNA fragments into the circulation, and some DNA fragments carry information that indicates their tissues-of-origin (TOOs). Based on the signals used for identifying the TOOs of cfDNAs, the existing methods can be classified into three categories: cfDNA mutation-based methods, methylation pattern-based methods and cfDNA fragmentation pattern-based methods. In cfDNA mutation-based methods, the SNP information or the detected mutations in driven genes of certain diseases are employed to identify the TOOs of cfDNAs. Methylation pattern-based methods are developed to identify the TOOs of cfDNAs based on the tissue-specific methylation patterns. In cfDNA fragmentation pattern-based methods, cfDNA fragmentation patterns, such as nucleosome positioning or preferred end coordinates of cfDNAs, are used to predict the TOOs of cfDNAs. In this paper, the strategies and challenges in each category are reviewed. Furthermore, the representative applications based on the TOOs of cfDNAs, including noninvasive prenatal testing, noninvasive cancer screening, transplantation rejection monitoring and parasitic infection detection, are also reviewed. Moreover, the challenges and future work in identifying the TOOs of cfDNAs are discussed. Our research provides a comprehensive picture of the development and challenges in identifying the TOOs of cfDNAs, which may benefit bioinformatics researchers to develop new methods to improve the identification of the TOOs of cfDNAs.
测序技术的进步促进了个性化疾病风险分析和临床诊断。近年来，基于游离 DNA（cfDNA）的非侵入性诊断取得了一些重大进展。它利用了这样一个事实，即死亡细胞会将 DNA 片段释放到循环中，而有些 DNA 片段携带有表明其组织来源（TOO）的信息。基于用于识别 cfDNA 的 TOO 的信号，现有的方法可以分为三类：基于 cfDNA 突变的方法、基于甲基化模式的方法和基于 cfDNA 片段化模式的方法。在基于 cfDNA 突变的方法中，使用特定疾病驱动基因中的 SNP 信息或检测到的突变来识别 cfDNA 的 TOO。基于甲基化模式的方法是基于组织特异性甲基化模式开发的，用于识别 cfDNA 的 TOO。在基于 cfDNA 片段化模式的方法中，cfDNA 片段化模式，如核小体定位或 cfDNA 的首选末端坐标，用于预测 cfDNA 的 TOO。本文综述了每一类方法的策略和挑战。此外，还综述了基于 cfDNA 的 TOO 的代表性应用，包括无创产前检测、无创癌症筛查、移植排斥监测和寄生虫感染检测。此外，还讨论了识别 cfDNA 的 TOO 所面临的挑战和未来工作。我们的研究提供了识别 cfDNA 的 TOO 的发展和挑战的全面概述，这可能有助于生物信息学研究人员开发新方法来提高识别 cfDNA 的 TOO 的能力。
