Title
A comprehensive comparison of residue-level methylation levels with the regression-based gene-level methylation estimations by ReGear
Abstract
Motivation: DNA methylation is a biological process impacting the gene functions without changing the underlying DNA sequence. The DNA methylation machinery usually attaches methyl groups to some specific cytosine residues, which modify the chromatin architectures. Such modifications in the promoter regions will inactivate some tumor-suppressor genes. DNA methylation within the coding region may significantly reduce the transcription elongation efficiency. The gene function may be tuned through some cytosines are methylated. Methods: This study hypothesizes that the overall methylation level across a gene may have a better association with the sample labels like diseases than the methylations of individual cytosines. The gene methylation level is formulated as a regression model using the methylation levels of all the cytosines within this gene. A comprehensive evaluation of various feature selection algorithms and classification algorithms is carried out between the gene-level and residue-level methylation levels. Results: A comprehensive evaluation was conducted to compare the gene and cytosine methylation levels for their associations with the sample labels and classification performances. The unsupervised clustering was also improved using the gene methylation levels. Some genes demonstrated statistically significant associations with the class label, even when no residue-level methylation features have statistically significant associations with the class label. So in summary, the trained gene methylation levels improved various methylome-based machine learning models. Both methodology development of regression algorithms and experimental validation of the gene-level methylation biomarkers are worth of further investigations in the future studies.
Year
DOI
Venue
2021
10.1093/bib/bbaa253
BRIEFINGS IN BIOINFORMATICS
Keywords
DocType
Volume
regression, ReGear, differential methylation, feature selection, classification, hierarchical clustering
Journal
22
Issue
ISSN
Citations 
4
1467-5463
0
PageRank 
References 
Authors
0.34
0
10
Name
Order
Citations
PageRank
Jinpu Cai100.34
Yuyang Xu200.34
Wen Zhang300.34
Shiying Ding400.34
Yuewei Sun500.34
Jingyi Lyu600.34
Meiyu Duan704.06
Shuai Liu801.35
Huang Lan91013.31
Fengfeng Zhou108312.36