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用于药物发现和药物开发的单细胞测序

Single-Cell Sequencing for Drug Discovery and Drug Development.

作者信息

Wu Hongjin, Wang Charles, Wu Shixiu

机构信息

Cancer Research Institute, Hangzhou Cancer Hospital, Hangzhou, 320000, Zhejiang Province, P.R. China

Center for Genomics & Department of Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA

出版信息

Curr Top Med Chem. 2017;17(15):1769-1777. doi: 10.2174/1568026617666161116145358.

Abstract

Next-generation sequencing (NGS), particularly single-cell sequencing, has revolutionized the scale and scope of genomic and biomedical research. Recent technological advances in NGS and singlecell studies have made the deep whole-genome (DNA-seq), whole epigenome and whole-transcriptome sequencing (RNA-seq) at single-cell level feasible. NGS at the single-cell level expands our view of genome, epigenome and transcriptome and allows the genome, epigenome and transcriptome of any organism to be explored without a priori assumptions and with unprecedented throughput. And it does so with single-nucleotide resolution. NGS is also a very powerful tool for drug discovery and drug development. In this review, we describe the current state of single-cell sequencing techniques, which can provide a new, more powerful and precise approach for analyzing effects of drugs on treated cells and tissues. Our review discusses single-cell whole genome/exome sequencing (scWGS/scWES), single-cell transcriptome sequencing (scRNA-seq), single-cell bisulfite sequencing (scBS), and multiple omics of single-cell sequencing. We also highlight the advantages and challenges of each of these approaches. Finally, we describe, elaborate and speculate the potential applications of single-cell sequencing for drug discovery and drug development.

摘要

下一代测序(NGS),尤其是单细胞测序,已经彻底改变了基因组学和生物医学研究的规模和范围。NGS和单细胞研究领域的最新技术进展使得在单细胞水平进行深度全基因组测序(DNA测序)、全表观基因组测序和全转录组测序(RNA测序)成为可能。单细胞水平的NGS拓展了我们对基因组、表观基因组和转录组的认识,使我们能够在无需先验假设的情况下以前所未有的通量探索任何生物体的基因组、表观基因组和转录组,而且能达到单核苷酸分辨率。NGS也是药物发现和药物开发的一项非常强大的工具。在本综述中,我们描述了单细胞测序技术的现状,这些技术能够为分析药物对处理后的细胞和组织的作用提供一种全新、更强大且精确的方法。我们的综述讨论了单细胞全基因组/外显子组测序(scWGS/scWES)、单细胞转录组测序(scRNA测序)、单细胞亚硫酸氢盐测序(scBS)以及单细胞测序的多组学研究。我们还强调了这些方法各自的优势和挑战。最后,我们描述、阐述并推测了单细胞测序在药物发现和药物开发中的潜在应用。

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