TY - JOUR
T1 - Guide Positioning Sequencing identifies aberrant DNA methylation patterns that alter cell identity and tumor-immune surveillance networks
AU - Li, Jin
AU - Li, Yan
AU - Li, Wei
AU - Luo, Huaibing
AU - Xi, Yanping
AU - Dong, Shihua
AU - Gao, Ming
AU - Xu, Peng
AU - Zhang, Baolong
AU - Liang, Ying
AU - Zou, Qingping
AU - Hu, Xin
AU - Peng, Lina
AU - Zou, Dan
AU - Wang, Ting
AU - Yang, Hongbo
AU - Jiang, Cizhong
AU - Peng, Shaoliang
AU - Wu, Feizhen
AU - Yu, Wenqiang
N1 - Publisher Copyright:
© 2019 Li et al.
PY - 2019/2
Y1 - 2019/2
N2 - 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-genomeDNAmethylation with cytosine coverage as high as96% 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 DNAmethylation and genomic variation. Using GPS, we show that aberrantDNA methylation is associated with altering cell identity and immune surveillance networks, which may contribute to tumorigenesis and metastasis.
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-genomeDNAmethylation with cytosine coverage as high as96% 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 DNAmethylation and genomic variation. Using GPS, we show that aberrantDNA methylation is associated with altering cell identity and immune surveillance networks, which may contribute to tumorigenesis and metastasis.
UR - http://www.scopus.com/inward/record.url?scp=85060932660&partnerID=8YFLogxK
U2 - 10.1101/gr.240606.118
DO - 10.1101/gr.240606.118
M3 - Article
C2 - 30670627
AN - SCOPUS:85060932660
SN - 1088-9051
VL - 29
SP - 270
EP - 280
JO - Genome research
JF - Genome research
IS - 2
ER -