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基于新一代高通量技术的人类疾病组学研究策略

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  • 深圳华大基因研究院, 深圳 518083

收稿日期: 2011-04-28

  修回日期: 2011-06-24

  网络出版日期: 2011-07-29

基金资助

全基因组高分辨率中国(东亚)人群遗传变异图谱的绘制(编号:2011CB809200)

New-generation high-throughput technologies based ‘omics’ research strategy in human disease

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  • BGI-Shenzhen, Shenzhen 518083, China

Received date: 2011-04-28

  Revised date: 2011-06-24

  Online published: 2011-07-29

摘要

近年来, 包括第二代测序技术和蛋白质谱技术等在内的新一代高通量技术越来越多的应用于解决生物学问题尤其是人类疾病的研究。这种以数据为导向, 大规模、工业化的研究模式, 使得从基因组水平、转录组水平、蛋白质组水平等角度对疾病展开全方位、多层次的研究成为可能。文章综述了新一代高通量技术在DNA、RNA、表观遗传、宏基因组和蛋白质组水平的人类疾病研究进展以及在转化医学领域的应用。在基因组水平上, 外显子组测序是近年来持续的研究热点, 随着测序成本的不断降低, 全基因组重测序也越来越凸显了其在全基因组范围内检测大型结构变异的优势, 并使得个人基因组引领的个体化医疗逐渐成为可能。在转录组水平, 如小RNA测序技术可用来检测已知小RNA和预测新的小RNA, 这些小RNA不仅可以作为疾病诊断和预后的分子标志物, 在疾病治疗方面也具有无限潜力。在蛋白质组水平, 如目标蛋白质组学可以有目标地测定可能与疾病相关的特定蛋白质或多肽, 能够很好地应用于疾病的临床分期分型。文章进一步阐述了跨组学研究在疾病研究领域中的应用和发展趋势, 借助生物信息学分析方法进行多组学整合研究, 能更加系统地阐释疾病的发生及发展机理, 为疾病的诊断治疗提供强有力的工具。

本文引用格式

杨旭,焦睿,杨琳,吴莉萍,李英睿,王俊 . 基于新一代高通量技术的人类疾病组学研究策略[J]. 遗传, 2011 , 33(8) : 829 -846 . DOI: 10.3724/SP.J.1005.2011.00829

Abstract

In recent years, new-generation high-throughput technologies, including next-generation sequencing technology and mass spectrometry method, have been widely applied in solving biological problems, especially in human diseases field. This data driven, large-scale and industrialized research model enables the omnidirectional and multi-level study of human diseases from the perspectives of genomics, transcriptomics and proteomics levels, etc. In this paper, the latest development of the high-throughput technologies that applied in DNA, RNA, epigenomics, metagenomics including proteomics and some applications in translational medicine are reviewed. At genomics level, exome sequencing has been the hot spot of the recent research. However, the predominance of whole genome resequencing in detecting large structural variants within the whole genome level is coming to stand out as the drop of sequencing cost, which also makes it possible for personalized genome based medicine application. At trancriptomics level, e.g., small RNA sequencing can be used to detect known and predict unknown miRNA. Those small RNA could not only be the biomarkers for disease diagnosis and prognosis, but also show the potential of disease treatment. At proteomics level, e.g., target proteomics can be used to detect the possible disease-related protein or peptides, which can be useful index for clinical staging and typing. Furthermore, the application and development of trans-omics study in disease research are briefly introduced. By applying bioinformatics technologies for integrating multi-omics data, the mechanism, diagnosis and therapy of the disease are likely to be systemically explained and realized, so as to provide powerful tools for disease diagnosis and therapies.

参考文献

[1] Ng SB, Turner EH, Robertson PD, Flygare SD, Bigham AW, Lee C, Shaffer T, Wong M, Bhattacharjee A, Eichler EE, Bamshad M, Nickerson DA, Shendure J. Targeted capture and massively parallel sequencing of 12 human exomes. Nature, 2009, 461(7261): 272-276.
[2] Ng SB, Buckingham KJ, Lee C, Bigham AW, Tabor HK, Dent KM, Huff CD, Shannon PT, Jabs EW, Nickerson DA, Shendure J, Bamshad MJ. Exome sequencing identifies the cause of a mendelian disorder. Nat Genet, 2010, 42(1): 30-35.
[3] Bolze A, Byun M, McDonald D, Morgan NV, Abhyankar A, Premkumar L, Puel A, Bacon CM, Rieux-Laucat F, Pang K, Britland A, Abel L, Cant A, Maher ER, Riedl SJ, Hambleton S, Casanova JL. Whole-exome-sequencing-based discovery of human FADD deficiency. Am J Hum Genet, 2010, 87(6): 873-881.
[4] Wang JL, Yang X, Xia K, Hu ZM, Weng L, Jin X, Jiang H, Zhang P, Shen L, Guo JF, Li N, Li YR, Lei LF, Zhou J, Du J, Zhou YF, Pan Q, Wang J, Wang J, Li RQ, Tang BS. TGM6 identified as a novel causative gene of spi-nocerebellar ataxias using exome sequencing. Brain, 2010, 133(12): 3510-3518.
[5] Li YR, Vinckenbosch N, Tian G, Huerta-Sanchez E, Jiang T, Jiang H, Albrechtsen A, Andersen G, Cao HZ, Korneliussen T, Grarup N, Guo YR, Hellman I, Jin X, Li QB, Liu JT, Liu X, Sparsø T, Tang MF, Wu HL, Wu RH, Yu C, Zheng HC, Astrup A, Bolund L, Holmkvist J, Jørgensen T, Kristiansen K, Schmitz O, Schwartz TW, Zhang XQ, Li RQ, Yang HM, Wang J, Hansen T, Pedersen O, Nielsen R, Wang J. Resequencing of 200 human exomes identifies an excess of low-frequency non-synonymous coding variants. Nat Genet, 2010, 42(11): 969-972.
[6] Musunuru K, Pirruccello JP, Do R, Peloso GM, Guiducci C, Sougnez C, Garimella KV, Fisher S, Abreu J, Barry AJ, Fennell T, Banks E, Ambrogio L, Cibulskis K, Kernytsky A, Gonzalez E, Rudzicz N, Engert JC, DePristo MA, Daly MJ, Cohen JC, Hobbs HH, Altshuler D, Schonfeld G, Gabriel SB, Yue P, Kathiresan S. Exome sequencing, ANGPTL3 mutations, and familial combined hypolipidemia. N Engl J Med, 2010, 363(23): 2220-2227.
[7] Jones S, Wang TL, Shih IeM, Mao TL, Nakayama K, Roden R, Glas R, Slamon D, Diaz LA Jr, Vogelstein B, Kinzler KW, Velculescu VE, Papadopoulos N. Frequent mutations of chromatin remodeling gene ARID1A in ovarian clear cell carcinoma. Science, 2010, 330(6001): 228-231.
[8] Harbour JW, Onken MD, Roberson EDO, Duan SH, Cao L, Worley LA, Council ML, Matatall KA, Helms C, Bowcock AM. Frequent mutation of BAP1 in metastasizing uveal melanomas. Science, 2010, 330(6009): 1410- 1413.
[9] O'Roak BJ, Deriziotis P, Lee C, Vives L, Schwartz JJ, Girirajan S, Karakoc E, Mackenzie AP, Ng SB, Baker C, Rieder MJ, Nickerson DA, Bernier R, Fisher SE, Shendure J, Eichler EE. Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations. Nat Genet., 2011, 43(6): 585-589.
[10] Girard SL, Gauthier J, Noreau A, Xiong L, Zhou S, Jouan L, Dionne-Laporte A, Spiegelman D, Henrion E, Diallo O, Thibodeau P, Bachand I, Bao JY, Tong AH, Lin CH, Millet B, Jaafari N, Joober R, Dion PA, Lok S, Krebs MO, Rouleau GA. Increased exonic de novo mutation rate in individuals with schizophrenia. Nat Genet., 2011 Jul 10. doi: 10.1038/ng.886.
[Epub ahead of print]
[11] Ley TJ, Mardis ER, Ding L, Fulton B, McLellan MD, Chen K, Dooling D, Dunford-Shore BH, McGrath S, Hickenbotham M, Cook L, Abbott R, Larson DE, Koboldt DC, Pohl C, Smith S, Hawkins A,. DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome. Nature, 2008, 456(7218): 66-72.
[12] Mardis ER, Ding L, Dooling DJ, Larson DE, McLellan MD, Chen K, Koboldt DC, Fulton RS, Delehaunty KD, McGrath SD, Fulton LA, Locke DP, Magrini VJ, Abbott RM, Vickery TL, Reed JS, Robinson JS, Wylie T, Smith SM, Carmichael L. Recurring mutations found by sequencing an acute myeloid leukemia genome. N Engl J Med, 2
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