dna甲基化与疾病报告-36页.pdf

Determining and characterizing epigenomic patterns across cells and individuals 张世华 中国科学院数学与系统科学研究院 2017-06-16 Major interests Optimization, Statistics, Algorithm and Machine Learning for Knowledge Discovery Bioinformatics and Computational Biology Cancer genomics Epigenomics Network biology 2 Epigenetics Non-DNA sequence related, heritable mechanisms to control gene expressions. 3 DNA methylation (DNA甲基化) An epigenetic modification of the DNA sequence: adding a methyl group to the 5 position of cytosine (5mC) Primarily happens at CpG sites (C followed by a G), although non-CG methylation exists 4 DNA methylation (DNA甲基化) • In human genome, ~90% of CpG sites are fully methylated, except at CpG islands where methylation levels are typically low • Methylation of CpG islands in/near promoter region of gene can silence gene expression. • DNA methylation has high tissue-specificity. Often referred to as the “5th base”. 5 Technologies to measure DNA methylation • Microarray: Illunima Infinium 450k – covers ~450k CpG sites in the genome. • Capture-based or enrichment-based sequencing (MeDIP-seq): • Use methyl-binding proteins or antibodies to capture methylated DNA fragments, then sequence fragments. • Resolution is low: can typically quantify the amount of DNA methylation in 100-200 bp regions. • Bisulfite-conversion-based sequencing (BS-seq, RRBS) • Bisulfite treatment converts unmethylated C’s to T’s. • Sequencing converted data gives single-bp re