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journal article·2024-06Open access

Wemics: A Single‐Base Resolution Methylation Quantification Method for Enhanced Prediction of Epigenetic Regulation

Yi Liu, Jiani Yi, Pin Wu, Jun Zhang, Xufan Li, Jia Li, Liyuan Zhou, Yong Liu, Haiming Xu, Enguo Chen, Honghe Zhang, Mingyu Liang, Pengyuan Liu, Xiaoqing Pan, Yan Lu

Advanced Science· Volume 11· Issue 21
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Source abstract

Abstract

Abstract DNA methylation, an epigenetic mechanism that alters gene expression without changing DNA sequence, is essential for organism development and key biological processes like genomic imprinting and X‐chromosome inactivation. Despite tremendous efforts in DNA methylation research, accurate quantification of cytosine methylation remains a challenge. Here, a single‐base methylation quantification approach is introduced by weighting methylation of consecutive CpG sites (Wemics) in genomic regions. Wemics quantification of DNA methylation better predicts its regulatory impact on gene transcription and identifies differentially methylated regions (DMRs) with more biological relevance. Most Wemics‐quantified DMRs in lung cancer are epigenetically conserved and recurrently occurred in other primary cancers from The Cancer Genome Atlas (TCGA), and their aberrant alterations can serve as promising pan‐cancer diagnostic markers. It is further revealed that these detected DMRs are enriched in transcription factor (TF) binding motifs, and methylation of these TF binding motifs and TF expression synergistically regulate target gene expression. Using Wemics on epigenomic‐transcriptomic data from the large lung cancer cohort, a dozen novel genes with oncogenic potential are discovered that are upregulated by hypomethylation but overlooked by other quantification methods. These findings increase the understanding of the epigenetic mechanism by which DNA methylation regulates gene expression.
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Research context

OpenAlex topics: Epigenetics and DNA Methylation · Genetic Syndromes and Imprinting · RNA modifications and cancer

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province Department of Respiratory Medicine, Department of Clinical Laboratory Sir Run Run Shaw Hospital and Institute of Translational Medicine Zhejiang University School of Medicine Hangzhou Zhejiang 310016 China

Institute of Bioinformatics Zhejiang University Hangzhou 310058 China

Department of Thoracic Surgery The Second Affiliated Hospital Zhejiang University School of Medicine Zhejiang University Hangzhou 310009 China

Department of Physiology The University of Arizona Tucson AZ 85721 USA

Department of Pathology Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy Chinese Academy of Medical Sciences Zhejiang University School of Medicine Hangzhou 310058 China

Cancer center Zhejiang University Hangzhou 310058 China

Department of Mathematics Shanghai Normal University Shanghai 200233 China

Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases Department of Gynecologic Oncology Women's Hospital and Institute of Translational Medicine Zhejiang University School of Medicine Hangzhou Zhejiang 310029 China

Funding

National Natural Science Foundation of China · National Institutes of Health

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