E2M: A Deep Learning Framework for Associating Combinatorial Methylation Patterns with Gene Expression

Jianhao Peng; Idoia Ochoa; Olgica Milenkovic

doi:10.1101/527044

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Abstract

We focus on the new problem of determining which methylation patterns in gene promoters strongly associate with gene expression in cancer cells of different types. Although a number of results regarding the influence of methylation on expression data have been reported in the literature, our approach is unique in so far that it retrospectively predicts the combinations of methylated sites in promoter regions of genes that are reflected in the expression data. Reversing the traditional prediction order in many cases makes estimation of the model parameters easier, as real-valued data are used to predict categorical data, rather than vice-versa; in addition, our approach allows one to better assess the overall influence of methylation in modulating expression via state-of-the-art learning methods. For this purpose, we developed a novel neural network learning framework termed E²M (Expression-to-Methylation) to predict the status of different methylation sites in promoter regions of several bio-marker genes based on a sufficient statistics of the whole gene expression captured through Landmark genes. We ran our experiments on unquantized and quantized expression sets and neural network weights to illustrate the robustness of the method and reduce the storage footprint of the processing pipeline.