Detecting Blood Methylation Signatures in Response to Childhood Cancer Radiotherapy via Machine Learning Methods

Abstract

Radiotherapy is a helpful treatment for cancer, but it can also potentially cause changes in many molecules, resulting in adverse effects. Among these changes, the occurrence of abnormal DNA methylation patterns has alarmed scientists. To explore the influence of region-specific radiotherapy on blood DNA methylation, we designed a computational workflow by using machine learning methods that can identify crucial methylation alterations related to treatment exposure. Irrelevant methylation features from the DNA methylation profiles of 2052 childhood cancer survivors were excluded via the Boruta method, and the remaining features were ranked using the minimum redundancy maximum relevance method to generate feature lists. These feature lists were then fed into the incremental feature selection method, which uses a combination of deep forest, k-nearest neighbor, random forest, and decision tree to find the most important methylation signatures and build the best classifiers and classification rules. Several methylation signatures and rules have been discovered and confirmed, allowing for a better understanding of methylation patterns in response to different treatment exposures.