RT Journal
A1 Li, Jin
A1 Li, Yan
A1 Li, Wei
A1 Luo, Huaibing
A1 Xi, Yanping
A1 Dong, Shihua
A1 Gao, Ming
A1 Xu, Peng
A1 Zhang, Baolong
A1 Liang, Ying
A1 Zou, Qingping
A1 Hu, Xin
A1 Peng, Lina
A1 Zou, Dan
A1 Wang, Ting
A1 Yang, Hongbo
A1 Jiang, Cizhong
A1 Peng, Shaoliang
A1 Wu, Feizhen
A1 Yu, Wenqiang
T1 Guide Positioning Sequencing identifies aberrant DNA methylation patterns that alter cell identity and tumor-immune surveillance networks
JF Genome Research 
JO Genome Research 
YR 2019 
FD February 01 
VO 29 
IS 2 
SP 270 
OP 280 
DO 10.1101/gr.240606.118 
UL http://genome.cshlp.org/content/29/2/270.abstract 
AB Aberrant DNA methylation is a distinguishing feature of cancer. Yet, how methylation affects immune surveillance and tumor metastasis remains ambiguous. We introduce a novel method, Guide Positioning Sequencing (GPS), for precisely detecting whole-genome DNA methylation with cytosine coverage as high as 96% and unbiased coverage of GC-rich and repetitive regions. Systematic comparisons of GPS with whole-genome bisulfite sequencing (WGBS) found that methylation difference between gene body and promoter is an effective predictor of gene expression with a correlation coefficient of 0.67 (GPS) versus 0.33 (WGBS). Moreover, Methylation Boundary Shift (MBS) in promoters or enhancers is capable of modulating expression of genes associated with immunity and tumor metabolism. Furthermore, aberrant DNA methylation results in tissue-specific enhancer switching, which is responsible for altering cell identity during liver cancer development. Altogether, we demonstrate that GPS is a powerful tool with improved accuracy and efficiency over WGBS in simultaneously detecting genome-wide DNA methylation and genomic variation. Using GPS, we show that aberrant DNA methylation is associated with altering cell identity and immune surveillance networks, which may contribute to tumorigenesis and metastasis.