Format

Send to

Choose Destination
Genome Res. 2019 Feb;29(2):270-280. doi: 10.1101/gr.240606.118. Epub 2019 Jan 22.

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

Li J#1,2,3, Li Y#1,2,3, Li W#1,2,3, Luo H#1,2,3, Xi Y#1,2,3, Dong S#1,2,3, Gao M#4,5, Xu P1,2,3, Zhang B1,2,3, Liang Y1,2,3, Zou Q1,2,3, Hu X6, Peng L1,2,3, Zou D4,5, Wang T7,8, Yang H9,10, Jiang C11, Peng S4,5, Wu F12,13, Yu W1,2,3.

Author information

1
Shanghai Public Health Clinical Center and Department of General Surgery, Huashan Hospital, Cancer Metastasis Institute and Laboratory of RNA Epigenetics, Institute of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, 201508, China.
2
Department of Biochemistry and Molecular Biology, Shanghai Medical College, Key Laboratory of Ministry of Education, Department of Molecular Biology, Fudan University, Shanghai, 200032, China.
3
Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, 200433, China.
4
College of Computer Science and Electronic Engineering and National Supercomputing Centre in Changsha, Hunan University, Changsha 410082, China.
5
School of Computer Science, National University of Defense Technology, Changsha, 410073, China.
6
Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
7
Department of Genetics, Washington University School of Medicine, St. Louis, Missouri 63108, USA.
8
Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, Missouri 63108, USA.
9
Department of Biochemistry and Molecular Biology, College of Medicine, The Pennsylvania State University, Hershey, Pennsylvania 17033, USA.
10
Bioinformatics and Genomics Program, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
11
Institute of Translational Research, Tongji Hospital, the School of Life Sciences and Technology, Shanghai Key Laboratory of Signaling and Disease Research, the Collaborative Innovation Center for Brain Science, Tongji University, Shanghai, 200092, China.
12
Laboratory of Epigenetics, Institute of Biomedical Sciences, Fudan University, Shanghai 200032, China.
13
Children's Hospital of Fudan University, Shanghai, 201102, China.
#
Contributed equally

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-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.

PMID:
30670627
DOI:
10.1101/gr.240606.118

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center