Analyzing the cancer methylome through targeted bisulfite sequencing

Abstract

Bisulfite conversion of genomic DNA combined with next-generation sequencing (NGS) has become a very effective approach for mapping the whole-genome and sub-genome wide DNA methylation landscapes. However, whole methylome shotgun bisulfite sequencing is still expensive and not suitable for analyzing large numbers of human cancer specimens. Recent advances in the development of targeted bisulfite sequencing approaches offer several attractive alternatives. The characteristics and applications of these methods are discussed in this review article. In addition, the bioinformatic tools that can be used for sequence capture probe design as well as downstream sequence analyses are also addressed.

Keywords: ACBS-seq; AML; BSPP; CGI; COBRA; CpG island; DMH; DNA methylation; DREAM; ES; HELP; HpaII tiny fragment enrichment by ligation-mediated PCR; ICF; MALDI-TOF MS; MBD; MCA; MDS; MIRA; MIRA-seq; MRE-seq; MSP; MeDIP; MeDIP-seq; NGS; Next-generation sequencing; PCR; SHBS-seq; SHS; TBS-seq; Targeted bisulfite sequencing; WGBS-seq; acute myeloid leukemia; array capture bisulfite sequencing; bisulfite padlock probes; combined bisulfite and restriction analysis; differential methylation hybridization; digital restriction enzyme analysis of methylation; embryonic stem; immunodeficiency, centromere instability and facial anomalies; matrix-assisted laser desorption/ionization-time of flight mass spectrometry; methyl-binding domain; methylated CpG island amplification; methylated CpG island recovery assay; methylated CpG island recovery assay sequencing; methylated DNA immunoprecipitation; methylated DNA immunoprecipitation sequencing; methylation sensitive restriction enzyme sequencing; methylation specific PCR; myelodysplastic syndromes; next-generation sequencing; polymerase chain reaction; solution hybrid selection; solution hybrid selection bisulfite sequencing; targeted bisulfite sequencing; whole genome shotgun bisulfite sequencing.