A Machine Learning Approach to Predict Gene Regulatory Networks in Seed Development in Arabidopsis Using Time Series Gene Expression Data

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2016-07-08

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Virginia Tech

Abstract

Gene regulatory networks (GRNs) provide a natural representation of relationships between regulators and target genes. Though inferring GRN is a challenging task, many methods, including unsupervised and supervised approaches, have been developed in the literature. However, most of these methods target non-context-specific GRNs. Because the regulatory relationships consistently reprogram under different tissues or biological processes, non-context-specific GRNs may not fit some specific conditions. In addition, a detailed investigation of the prediction results has remained elusive. In this study, I propose to use a machine learning approach to predict GRNs that occur in developmental stage-specific networks and to show how it improves our understanding of the GRN in seed development.

I developed a Beacon GRN inference tool to predict a GRN in seed development in Arabidopsis based on a support vector machine (SVM) local model. Using the time series gene expression levels in seed development and prior known regulatory relationships, I evaluated and predicted the GRN at this specific biological process. The prediction results show that one gene may be controlled by multiple regulators. The targets that are strongly positively correlated with their regulators are mostly expressed at the beginning of seed development. The direct targets were detected when I found a match between the promoter regions of the targets and the regulator's binding sequence. Our prediction provides a novel testable hypotheses of a GRN in seed development in Arabidopsis, and the Beacon GRN inference tool provides a valuable model system for context-specific GRN inference.

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Network inference, signal transduction pathways, gene expression, support vector machines

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