通过新一代测序技术分析表观遗传修饰

Analysis of epigenetic modifications by next generation sequencing.

作者信息

Liang Shoudan, Lu Yue, Jelinek Jaroslav, Estecio Marcos, Li Hao, Issa Jean-Pierre

机构信息

Department of Bioinformatics and Computational Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.

出版信息

Annu Int Conf IEEE Eng Med Biol Soc. 2009;2009:6730. doi: 10.1109/IEMBS.2009.5332853.

DOI:10.1109/IEMBS.2009.5332853

PMID:19963934

Abstract

In plants and animals, gene expression can be altered by changes not to DNA itself but rather chemical modifications either to DNA or to histones that interact with DNA. These so called epigenetic modifications persist through cell cycle. Rapidly advancing technologies, such next generation DNA sequencing, have dramatically increased our ability to survey epigenetic markers genomewide. These techniques are revealing in great details massive epigenetic changes in cancer. Analysis of next generation sequencing data present a formidable computational challenge. We will discuss methods to address these challenges in the context of analyzing histone modifications and DNA methylation data. Several techniques useful in epigenetic data analysis will be discussed, mapping tags to reference genome incorporating all known SNPs, analysis of chIP-seq data, as well as restriction enzyme-based DNA methylation analysis.

摘要

在植物和动物中，基因表达的改变并非源于DNA本身的变化，而是源于对DNA或与DNA相互作用的组蛋白的化学修饰。这些所谓的表观遗传修饰在细胞周期中持续存在。快速发展的技术，如下一代DNA测序，极大地提高了我们在全基因组范围内检测表观遗传标记的能力。这些技术正详细揭示癌症中大量的表观遗传变化。分析下一代测序数据带来了巨大的计算挑战。我们将在分析组蛋白修饰和DNA甲基化数据的背景下讨论应对这些挑战的方法。还将讨论几种在表观遗传数据分析中有用的技术，将标签映射到包含所有已知单核苷酸多态性的参考基因组、分析染色质免疫沉淀测序（ChIP-seq）数据以及基于限制性酶的DNA甲基化分析。