Next-generation sequencing in aging research: emerging applications, problems, pitfalls and possible solutions.

Next-generation sequencing in aging research: emerging applications, problems, pitfalls and possible solutions.
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DOI:
10.1016/j.arr.2009.10.006
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发表时间:
2010-07
影响因子:
13.1
通讯作者:
Janssens, Georges
Janssens, Georges
中科院分区:
医学1区
文献类型:
--
作者:
de Magalhaes, Joao Pedro;Finch, Caleb E.;Janssens, Georges

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最近的技术进步使得 DNA 测序变得更快、更便宜,正在推动生物和医学研究。在这篇综述中,我们概述了最先进的下一代测序 (NGS) 平台及其应用,包括基因组测序和重测序、转录分析 (RNA-Seq) 以及 DNA-蛋白质相互作用 (ChIP-Seq) 和表观基因组的高通量调查。我们特别关注NGS带来的新方法如何帮助揭示衰老、长寿和年龄相关疾病的生物学和遗传机制。然而,同样地,NGS 平台开放了以前不可用的发现,它们也带来了新的挑战,特别是在处理、分析和解释数据方面。讨论了生物信息学和软件问题以及全基因组研究中的统计困难,以及使用靶向测序来降低成本并促进统计分析。最后,我们讨论了从大量数据中收集生物学见解的多种方法,例如功能富集、转录调控和网络分析。尽管在快速发展的 NGS 领域,新平台很快就会占据中心舞台,但 NGS 所实现的方法将在未来几年成为分子生物学、遗传学和系统生物学的基础,从而有助于衰老研究。
Recent technological advances that allow faster and cheaper DNA sequencing are now driving biological and medical research. In this review, we provide an overview of state-of-the-art next-generation sequencing (NGS) platforms and their applications, including in genome sequencing and resequencing, transcriptional profiling (RNA-Seq) and high-throughput survey of DNA-protein interactions (ChIP-Seq) and of the epigenome. Particularly, we focus on how new methods made possible by NGS can help unravel the biological and genetic mechanisms of aging, longevity and age-related diseases. In the same way, however, NGS platforms open discovery not available before, they also give rise to new challenges, in particular in processing, analyzing and interpreting the data. Bioinformatics and software issues plus statistical difficulties in genome-wide studies are discussed, as well as the use of targeted sequencing to decrease costs and facilitate statistical analyses. Lastly, we discuss a number of methods to gather biological insights from massive amounts of data, such as functional enrichment, transcriptional regulation and network analyses. Although in the fast-moving field of NGS new platforms will soon take center stage, the approaches made possible by NGS will be at the basis of molecular biology, genetics and systems biology for years to come, making them instrumental for research on aging.
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