Putative Origins of Cell-Free DNA in Humans: A Review of Active and Passive Nucleic Acid Release Mechanisms.
Putative Origins of Cell-Free DNA in Humans: A Review of Active and Passive Nucleic Acid Release Mechanisms.
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DOI：
10.3390/ijms21218062
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发表时间：
2020-10-29
影响因子：
5.6
通讯作者：
Sensen CW
中科院分区：
文献类型：
--
作者：
Grabuschnig S;Bronkhorst AJ;Holdenrieder S;Rosales Rodriguez I;Schliep KP;Schwendenwein D;Ungerer V;Sensen CW
通过细胞死亡、降解和调控挤压的各种途径，各种来源的部分或完整基因组（例如，宿主细胞、胎儿细胞和浸润的病毒和微生物）以分节的无细胞DNA （cfDNA）分子的形式不断脱落到人体体液中。虽然总cfDNA的遗传复杂性是巨大的，但逐步高效提取，高通量测序，通过生物信息学程序表征和检测的发展已经导致cfDNA亚型的越来越准确的划分和分析。毫不奇怪，cfDNA分析正在成为医学许多分支中强大的临床工具。此外，纵向cfDNA采样的低侵入性为研究各种背景下的时间基因组变化提供了前所未有的途径。然而，cfDNA的遗传多样性也是模糊性的一个重要来源，并提出了重大的实验和分析挑战。例如，血液中的cfDNA种群是异质的，也会动态波动，在个体之间是不同的，尽管通常来自不同的来源和过程，但仍表现出许多重叠的特征。因此，更深入地了解影响cfDNA特性的决定变量是至关重要的，然而，到目前为止，在很大程度上是缺乏的。在这项工作中，我们回顾了最近和历史上关于主动和被动释放机制的研究，并估计了它们对cfDNA组成的贡献的重要性和程度。
Through various pathways of cell death, degradation, and regulated extrusion, partial or complete genomes of various origins (e.g., host cells, fetal cells, and infiltrating viruses and microbes) are continuously shed into human body fluids in the form of segmented cell-free DNA (cfDNA) molecules. While the genetic complexity of total cfDNA is vast, the development of progressively efficient extraction, high-throughput sequencing, characterization via bioinformatics procedures, and detection have resulted in increasingly accurate partitioning and profiling of cfDNA subtypes. Not surprisingly, cfDNA analysis is emerging as a powerful clinical tool in many branches of medicine. In addition, the low invasiveness of longitudinal cfDNA sampling provides unprecedented access to study temporal genomic changes in a variety of contexts. However, the genetic diversity of cfDNA is also a great source of ambiguity and poses significant experimental and analytical challenges. For example, the cfDNA population in the bloodstream is heterogeneous and also fluctuates dynamically, differs between individuals, and exhibits numerous overlapping features despite often originating from different sources and processes. Therefore, a deeper understanding of the determining variables that impact the properties of cfDNA is crucial, however, thus far, is largely lacking. In this work we review recent and historical research on active vs. passive release mechanisms and estimate the significance and extent of their contribution to the composition of cfDNA.
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DOI：
10.1126/science.aao4227
发表时间：
2018-09-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Albrengues J;Shields MA;Ng D;Park CG;Ambrico A;Poindexter ME;Upadhyay P;Uyeminami DL;Pommier A;Küttner V;Bružas E;Maiorino L;Bautista C;Carmona EM;Gimotty PA;Fearon DT;Chang K;Lyons SK;Pinkerton KE;Trotman LC;Goldberg MS;Yeh JT;Egeblad M
通讯作者：
Egeblad M
影响因子：
14.9
作者：
Bailey SM;Murnane JP
通讯作者：
Murnane JP
影响因子：
8
作者：
Aucamp, Janine;Bronkhorst, Abel J.;Pretorius, Piet J.
通讯作者：
Pretorius, Piet J.
影响因子：
9.3
作者：
Beck, Julia;Urnovitz, Howard B.;Schuetz, Ekkehard
通讯作者：
Schuetz, Ekkehard
影响因子：
6.6
作者：
Bayraktar R;Van Roosbroeck K;Calin GA
通讯作者：
Calin GA