Application of cell-free DNA sequencing in characterization of bloodborne microbes and the study of microbe-disease interactions
Application of cell-free DNA sequencing in characterization of bloodborne microbes and the study of microbe-disease interactions
复制标题
DOI：
10.7717/peerj.7426
复制
发表时间：
2019-08-06
期刊：
影响因子：
2.7
通讯作者：
Yu, Alice L.
中科院分区：
文献类型：
--
作者：
Chiu, Kuo-Ping;Yu, Alice L.
微生物能否与心血管系统正常细胞和谐共存是一个重要的问题。这个问题的答案将对医学微生物学产生巨大的影响。为了解决这个问题，必须以有效和全面的方式识别和表征血源性微生物。由于微生物序列的复杂性和循环系统中大量未知微生物物种的组成，使用细胞培养、PCR或微阵列的传统方法不适用于该目的。最近的报告表明，使用下一代测序（NGS）或单分子测序（SMS）的无细胞DNA（cfDNA）测序，以及生物信息学方法，具有强大的潜力，使我们能够在核苷酸水平上区分微生物物种。使用微生物cfDNA测序来鉴定脓毒症患者的微生物的多项研究已显示与细胞培养的高度一致。类似的方法也被应用于揭示以前未鉴定的微生物或证明对健康和/或患病个体的血源性微生物进行综合评估的可行性。使用SMRT（单分子实时）测序或纳米孔测序的SMS为加强这一研究提供了新的动力。总之，微生物cfDNA测序提供了一个新的机会，使我们能够进一步了解血液传播微生物在疾病发展中的作用。类似的方法也应该适用于宏基因组学的研究，以充分和全面地分析生活在各种环境中的微生物物种。本文回顾了这一系列研究，并讨论了已经开发或可能在未来开发的方法学方法，这些方法可能具有强大的潜力，以促进基于cfDNA和cfRNA的癌症和急性/慢性疾病研究，希望更好地了解循环系统中隐藏的微生物将改善诊断，预防和治疗问题性疾病。
It is an important issue whether microorganisms can live harmoniously with normal ells in the cardiovascular system. The answer to the question will have enormous impact on medical microbiology. To address the issue, it is essential to identify and characterize the bloodborne microbes in an efficient and comprehensive manner. Due to microbial sequence complexity and the composition of significant number of unknown microbial species in the circulatory system, traditional approaches using cell culture, PCR, or microarray are not suitable for the purpose. Recent reports indicate that cell-free DNA (cfDNA) sequencing using next-generation sequencing (NGS) or single-molecule sequencing (SMS), together with bioinformatics approaches, possesses a strong potential enabling us to distinguish microbial species at the nucleotide level. Multiple studies using microbial cfDNA sequencing to identify microbes for septic patients have shown strong agreement with cell culture. Similar approaches have also been applied to reveal previously unidentified microorganisms or to demonstrate the feasibility of comprehensive assessment of bloodborne microorganisms for healthy and/or diseased individuals. SMS using either SMRT (single-molecule real-time) sequencing or Nanopore sequencing are providing new momentum to reinforce this line of investigation. Taken together, microbial cfDNA sequencing provides a novel opportunity allowing us to further understand the involvement of bloodborne microbes in development of diseases. Similar approaches should also be applicable to the study of metagenomics for sufficient and comprehensive analysis of microbial species living in various environments. This article reviews this line of research and discuss the methodological approaches that have been developed, or are likely to be developed in the future, which may have strong potential to facilitate cfDNA- and cfRNA-based studies of cancer and acute/chronic diseases, in the hope that a better understanding of the hidden microbes in the circulatory system will improve diagnosis, prevention and treatment of problematic diseases.