TY - GEN
T1 - A computational framework to simultaneously quantify DNA methylation, somatic copy number alternation and DNA heterogeneity from low coverage plasma circulating DNA sequencing
AU - Yao, Pengfei
AU - Cheng, Long
AU - Lu, Jianwei
AU - Hao, Ke
AU - Zhang, Zhongyang
N1 - Funding Information:
This work is partially supported by National Natural Science Foundation of China (Grant No. 21477087, 91643201) and by the Ministry of Science and Technology of China (Grant No. 2016YFC0206507). The authors thank Dr. Y. M. Dennis Lo and colleagues for sharing the WGBS data and Methy-Pipe tools.
Publisher Copyright:
© 2018 Association for Computing Machinery.
PY - 2018/3/12
Y1 - 2018/3/12
N2 - Genome of Hepatocellular Carcinoma (HCC) undergoes profound changes, including DNA hypomethylation and somatic copy number alternations (SCNA). These two characteristics provide orthogonal information for HCC early diagnosis, and can be assessed by whole-genome bisulfite sequencing (WGBS) of the plasma circulating DNA. We proposed a computational framework to simultaneously quantify DNA methylation and SCNA from plasma circulating DNA WGBS, and further estimate the heterogeneity of the circulating DNA. Our approach reliably detected global DNA hypomethylation and SCNA from low coverage WGBS of tumor and plasma circulating DNA from HCC subjects compared to healthy control individuals. The chromosomal pattern of SCNA detected from tumor DNA and plasma DNA are highly consistent. The computational framework we proposed make efficient use of WGBS and able to simultaneously characterize DNA hypomethylation SCNA, which provide orthogonal evidence in HCC early diagnosis. Importantly, our approach estimated the tumor DNA fraction in plasma circulating DNA, ranging from 38.55% to 1.79%, and is correlated with tumor size (Spearman's correlation coefficient = 0.68, p-value=0.0049). We estimate that the tumor DNA content in plasma could be below 2% for HCC tumor of 2cm or smaller in diameter, which requires relatively high coverage WGBS for reliable assessment.
AB - Genome of Hepatocellular Carcinoma (HCC) undergoes profound changes, including DNA hypomethylation and somatic copy number alternations (SCNA). These two characteristics provide orthogonal information for HCC early diagnosis, and can be assessed by whole-genome bisulfite sequencing (WGBS) of the plasma circulating DNA. We proposed a computational framework to simultaneously quantify DNA methylation and SCNA from plasma circulating DNA WGBS, and further estimate the heterogeneity of the circulating DNA. Our approach reliably detected global DNA hypomethylation and SCNA from low coverage WGBS of tumor and plasma circulating DNA from HCC subjects compared to healthy control individuals. The chromosomal pattern of SCNA detected from tumor DNA and plasma DNA are highly consistent. The computational framework we proposed make efficient use of WGBS and able to simultaneously characterize DNA hypomethylation SCNA, which provide orthogonal evidence in HCC early diagnosis. Importantly, our approach estimated the tumor DNA fraction in plasma circulating DNA, ranging from 38.55% to 1.79%, and is correlated with tumor size (Spearman's correlation coefficient = 0.68, p-value=0.0049). We estimate that the tumor DNA content in plasma could be below 2% for HCC tumor of 2cm or smaller in diameter, which requires relatively high coverage WGBS for reliable assessment.
KW - DNA methylation
KW - Hepatocellular carcinoma
KW - Next generation sequencing
KW - Plasma circulating DNA
KW - Somatic copy number alternations
UR - http://www.scopus.com/inward/record.url?scp=85047137643&partnerID=8YFLogxK
U2 - 10.1145/3194480.3194483
DO - 10.1145/3194480.3194483
M3 - Conference contribution
AN - SCOPUS:85047137643
T3 - ACM International Conference Proceeding Series
SP - 7
EP - 13
BT - Proceedings of 2018 6th International Conference on Bioinformatics and Computational Biology, ICBCB 2018
PB - Association for Computing Machinery
T2 - 6th International Conference on Bioinformatics and Computational Biology, ICBCB 2018
Y2 - 12 March 2018 through 14 March 2018
ER -