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

doi:10.1101/gr.240606.118

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

^*Corresponding author for this work

Biochemistry and Molecular Genetics

Research output: Contribution to journal › Article › peer-review

26 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 language	English (US)
Pages (from-to)	270-280
Number of pages	11
Journal	Genome research
Volume	29
Issue number	2
DOIs	https://doi.org/10.1101/gr.240606.118
State	Published - Feb 2019

Funding

We thank Guoming Shi for supplying hepatoma cell lines 97L and LM3.We thank Yue Yu for manuscript revision and careful reading of the manuscript.We thank Yao Xiao, Min Xiao, Xiaoguang Ren, Lan Zhang, Liping Zhao, RuKui Zhang, and Shuzheng Song for editorial help and comments on the manuscript. This work was supported by the Ministry of Science and Technology (Grant Nos. 2016YFC0900303 and 2018YFC1005004), Major Special Projects of Basic Research of Shanghai Science and Technology Commission (Grant No. 18JC1411101), the Science and Technology Innovation Action Plan of Shanghai (Grant No. 17411950900), the National Natural Science Foundation of China (Grant Nos. 31671308, 31872814, and 81272295), the Shanghai Science and Technology Committee (Grant No. 12ZR1402200), the National High-tech R&D program, 863 Program (Grant No. 2015AA020108), the National Key Research and Development Program of China (Grant No. 2016YFC1000500), the Ministry of Education of the People's Republic of China (Grant No. 2009CB825600), and the National Key R and D Program of China (Grant No. 2018YFC0910405). 2009CB825600), and the National Key R&D Program of China (Grant No. 2018YFC0910405). We thank Guoming Shi for supplying hepatoma cell lines 97L and LM3. We thank Yue Yu for manuscript revision and careful reading of the manuscript. We thank Yao Xiao, Min Xiao, Xiaoguang Ren, Lan Zhang, Liping Zhao, RuKui Zhang, and Shuzheng Song for editorial help and comments on the manuscript. This work was supported by the Ministry of Science and Technology (Grant Nos. 2016YFC0900303 and 2018YFC1005004), Major Special Projects of Basic Research of Shanghai Science and Technology Commission (Grant No. 18JC1411101), the Science and Technology Innovation Action Plan of Shanghai (Grant No. 17411950900), the National Natural Science Foundation of China (Grant Nos. 31671308, 31872814, and 81272295), the Shanghai Science and Technology Committee (Grant No. 12ZR1402200), the National High-tech R&D program, 863 Program (Grant No. 2015AA020108), the National Key Research and Development Program of China (Grant No. 2016YFC1000500), the Ministry of Education of the People’s Republic of China (Grant No.

ASJC Scopus subject areas

Genetics
Genetics(clinical)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1101/gr.240606.118

Cite this

Li, J., Li, Y., Li, W., Luo, H., Xi, Y., Dong, S., Gao, M., Xu, P., Zhang, B., Liang, Y., Zou, Q., Hu, X., Peng, L., Zou, D., Wang, T., Yang, H., Jiang, C., Peng, S., Wu, F., & Yu, W. (2019). Guide Positioning Sequencing identifies aberrant DNA methylation patterns that alter cell identity and tumor-immune surveillance networks. Genome research, 29(2), 270-280. https://doi.org/10.1101/gr.240606.118

@article{108262fd088243c69b81801d46938446,

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

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.",

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

note = "Funding Information: We thank Guoming Shi for supplying hepatoma cell lines 97L and LM3.We thank Yue Yu for manuscript revision and careful reading of the manuscript.We thank Yao Xiao, Min Xiao, Xiaoguang Ren, Lan Zhang, Liping Zhao, RuKui Zhang, and Shuzheng Song for editorial help and comments on the manuscript. This work was supported by the Ministry of Science and Technology (Grant Nos. 2016YFC0900303 and 2018YFC1005004), Major Special Projects of Basic Research of Shanghai Science and Technology Commission (Grant No. 18JC1411101), the Science and Technology Innovation Action Plan of Shanghai (Grant No. 17411950900), the National Natural Science Foundation of China (Grant Nos. 31671308, 31872814, and 81272295), the Shanghai Science and Technology Committee (Grant No. 12ZR1402200), the National High-tech R&D program, 863 Program (Grant No. 2015AA020108), the National Key Research and Development Program of China (Grant No. 2016YFC1000500), the Ministry of Education of the People's Republic of China (Grant No. 2009CB825600), and the National Key R and D Program of China (Grant No. 2018YFC0910405). Funding Information: 2009CB825600), and the National Key R&D Program of China (Grant No. 2018YFC0910405). Funding Information: We thank Guoming Shi for supplying hepatoma cell lines 97L and LM3. We thank Yue Yu for manuscript revision and careful reading of the manuscript. We thank Yao Xiao, Min Xiao, Xiaoguang Ren, Lan Zhang, Liping Zhao, RuKui Zhang, and Shuzheng Song for editorial help and comments on the manuscript. This work was supported by the Ministry of Science and Technology (Grant Nos. 2016YFC0900303 and 2018YFC1005004), Major Special Projects of Basic Research of Shanghai Science and Technology Commission (Grant No. 18JC1411101), the Science and Technology Innovation Action Plan of Shanghai (Grant No. 17411950900), the National Natural Science Foundation of China (Grant Nos. 31671308, 31872814, and 81272295), the Shanghai Science and Technology Committee (Grant No. 12ZR1402200), the National High-tech R&D program, 863 Program (Grant No. 2015AA020108), the National Key Research and Development Program of China (Grant No. 2016YFC1000500), the Ministry of Education of the People{\textquoteright}s Republic of China (Grant No. Publisher Copyright: {\textcopyright} 2019 Li et al.",

year = "2019",

month = feb,

doi = "10.1101/gr.240606.118",

language = "English (US)",

volume = "29",

pages = "270--280",

journal = "Genome research",

issn = "1088-9051",

publisher = "Cold Spring Harbor Laboratory Press",

number = "2",

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Li, J, Li, Y, Li, W, Luo, H, Xi, Y, Dong, S, Gao, M, Xu, P, Zhang, B, Liang, Y, Zou, Q, Hu, X, Peng, L, Zou, D, Wang, T, Yang, H, Jiang, C, Peng, S, Wu, F & Yu, W 2019, 'Guide Positioning Sequencing identifies aberrant DNA methylation patterns that alter cell identity and tumor-immune surveillance networks', Genome research, vol. 29, no. 2, pp. 270-280. https://doi.org/10.1101/gr.240606.118

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 - Funding Information: We thank Guoming Shi for supplying hepatoma cell lines 97L and LM3.We thank Yue Yu for manuscript revision and careful reading of the manuscript.We thank Yao Xiao, Min Xiao, Xiaoguang Ren, Lan Zhang, Liping Zhao, RuKui Zhang, and Shuzheng Song for editorial help and comments on the manuscript. This work was supported by the Ministry of Science and Technology (Grant Nos. 2016YFC0900303 and 2018YFC1005004), Major Special Projects of Basic Research of Shanghai Science and Technology Commission (Grant No. 18JC1411101), the Science and Technology Innovation Action Plan of Shanghai (Grant No. 17411950900), the National Natural Science Foundation of China (Grant Nos. 31671308, 31872814, and 81272295), the Shanghai Science and Technology Committee (Grant No. 12ZR1402200), the National High-tech R&D program, 863 Program (Grant No. 2015AA020108), the National Key Research and Development Program of China (Grant No. 2016YFC1000500), the Ministry of Education of the People's Republic of China (Grant No. 2009CB825600), and the National Key R and D Program of China (Grant No. 2018YFC0910405). Funding Information: 2009CB825600), and the National Key R&D Program of China (Grant No. 2018YFC0910405). Funding Information: We thank Guoming Shi for supplying hepatoma cell lines 97L and LM3. We thank Yue Yu for manuscript revision and careful reading of the manuscript. We thank Yao Xiao, Min Xiao, Xiaoguang Ren, Lan Zhang, Liping Zhao, RuKui Zhang, and Shuzheng Song for editorial help and comments on the manuscript. This work was supported by the Ministry of Science and Technology (Grant Nos. 2016YFC0900303 and 2018YFC1005004), Major Special Projects of Basic Research of Shanghai Science and Technology Commission (Grant No. 18JC1411101), the Science and Technology Innovation Action Plan of Shanghai (Grant No. 17411950900), the National Natural Science Foundation of China (Grant Nos. 31671308, 31872814, and 81272295), the Shanghai Science and Technology Committee (Grant No. 12ZR1402200), the National High-tech R&D program, 863 Program (Grant No. 2015AA020108), the National Key Research and Development Program of China (Grant No. 2016YFC1000500), the Ministry of Education of the People’s Republic of China (Grant No. 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.

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

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