Guide Positioning Sequencing identifies aberrant DNA methylation patterns that alter cell identity and tumor-immune surveillance networks

Jin Li, Yan Li, Wei Li, Huaibing Luo, Yanping Xi, Shihua Dong, Ming Gao, Peng Xu, Baolong Zhang, Ying Liang, Qingping Zou, Xin Hu, Lina Peng, Dan Zou, Ting Wang, Hongbo Yang, Cizhong Jiang, Shaoliang Peng, Feizhen Wu, Wenqiang Yu

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)270-280
Number of pages11
JournalGenome research
Volume29
Issue number2
DOIs
StatePublished - Feb 2019

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

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