Single-molecule optical genome mapping in nanochannels: multidisciplinarity at the nanoscale.
Single-molecule optical genome mapping in nanochannels: multidisciplinarity at the nanoscale.
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纳米通道中的单分子光学基因组定位：纳米尺度下的多学科。
DOI：
10.1042/ebc20200021
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发表时间：
2021-04-16
影响因子：
6.4
通讯作者：
Ebenstein Y
中科院分区：
文献类型：
--
作者：
Jeffet J;Margalit S;Michaeli Y;Ebenstein Y
人类基因组包含了超越基因序列的多层信息。事实上，相同的遗传学并不一定产生相同的表型，这对于人体中两种不同细胞类型的情况是显而易见的。具有相同遗传背景的细胞在结构和功能上的巨大差异归因于额外的基因组信息含量。这包括大规模的遗传畸变，以及对调节特定细胞功能至关重要的多种表观遗传模式。这些遗传和表观遗传模式协同运作，以维持健康和疾病中的特定细胞功能。单分子光学基因组作图是一种高通量基因组分析方法，其基于对在纳米通道阵列中拉伸的长染色体片段进行成像。获得长DNA分子加上荧光标记的各种基因组信息提供了一个独特的机会，研究基因组中的遗传和表观遗传模式，在单分子水平上在大的基因组距离。光学映射协同地缠绕化学，物理和计算进步，以揭示测序技术无法获得的宝贵的生物学见解。在这里，我们描述了该方法的基本操作原理，并回顾了各种可用的机制，荧光标记基因组信息。我们提出了一些最近的生物学和临床的影响，使光学映射和目前最近的方法，以提高该方法的分辨率和准确性。最后，我们讨论了如何多层的基因组信息可以同时映射到同一个DNA分子上，从而为表征单个DNA分子上的多个基因组观测值铺平了道路。
The human genome contains multiple layers of information that extend beyond the genetic sequence. In fact, identical genetics do not necessarily yield identical phenotypes as evident for the case of two different cell types in the human body. The great variation in structure and function displayed by cells with identical genetic background is attributed to additional genomic information content. This includes large-scale genetic aberrations, as well as diverse epigenetic patterns that are crucial for regulating specific cell functions. These genetic and epigenetic patterns operate in concert in order to maintain specific cellular functions in health and disease. Single-molecule optical genome mapping is a high-throughput genome analysis method that is based on imaging long chromosomal fragments stretched in nanochannel arrays. The access to long DNA molecules coupled with fluorescent tagging of various genomic information presents a unique opportunity to study genetic and epigenetic patterns in the genome at a single-molecule level over large genomic distances. Optical mapping entwines synergistically chemical, physical, and computational advancements, to uncover invaluable biological insights, inaccessible by sequencing technologies. Here we describe the method’s basic principles of operation, and review the various available mechanisms to fluorescently tag genomic information. We present some of the recent biological and clinical impact enabled by optical mapping and present recent approaches for increasing the method’s resolution and accuracy. Finally, we discuss how multiple layers of genomic information may be mapped simultaneously on the same DNA molecule, thus paving the way for characterizing multiple genomic observables on individual DNA molecules.