期刊
CURRENT BIOINFORMATICS
卷 16, 期 2, 页码 179-196出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1574893615999200724145835
关键词
CpG island; methylation; predictive model; unbiased learning; sequence signature; DNA motif
This study aimed to develop machine learning models to predict the methylation propensity of CGIs, with results indicating that combined features in the model provide more accurate predictions. This can lead to a better understanding of disease mechanisms, gene classification based on methylation propensity, and potential preventative treatment strategies.
Background: Epigenetic repression mechanisms play an important role in gene regulation, specifically in cancer development. In many cases, a CpG island's (CGI) susceptibility or resistance to methylation is shown to be contributed by local DNA sequence features. Objective: To develop unbiased machine learning models-individually and combined for different biological features-that predict the methylation propensity of a CGI. Methods: We developed our model consisting of CGI sequence features on a dataset of 75 sequences (28 prone, 47 resistant) representing a genome-wide methylation structure. We tested our model on two independent datasets that are chromosome (132 sequences) and disease (70 sequences) specific. Results: We provided improvements in prediction accuracy over previous models. Our results indicate that combined features better predict the methylation propensity of a CGI (area under the curve (AUC) similar to 0.81). Our global methylation classifier performs well on independent datasets reaching an AUC of similar to 0.82 for the complete model and an AUC of similar to 0.88 for the model using select sequences that better represent their classes in the training set. We report certain de novo motifs and transcription factor binding site (TFBS) motifs that are consistently better in separating prone and resistant CGIs. Conclusion: Predictive models for the methylation propensity of CGIs lead to a better understanding of disease mechanisms and can be used to classify genes based on their tendency to contain methylation prone CGIs, which may lead to preventative treatment strategies.
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