Machine Learning Approaches for Identifying microRNA Targets and Conserved Protein Complexes

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Virginia Tech

Much research has been directed toward understanding the roles of essential components in the cell, such as proteins, microRNAs, and genes. This dissertation focuses on two interesting problems in bioinformatics research: microRNA-target prediction and the identification of conserved protein complexes across species. We define the two problems and develop novel approaches for solving them. MicroRNAs are short non-coding RNAs that mediate gene expression. The goal is to predict microRNA targets. Existing methods rely on sequence features to predict targets. These features are neither sufficient nor necessary to identify functional target sites and ignore the cellular conditions in which microRNA and mRNA interact. We developed MicroTarget to predict microRNA-mRNA interactions using heterogeneous data sources. MicroTarget uses expression data to learn candidate target set for each microRNA. Then, sequence data is used to provide evidence of direct interactions and ranking the predicted targets. The predicted targets overlap with many of the experimentally validated ones. The results indicate that using expression data helps in predicting microRNA targets accurately.

Protein complexes conserved across species specify processes that are core to cell machinery. Methods that have been devised to identify conserved complexes are severely limited by noise in PPI data. Behind PPIs, there are domains interacting physically to perform the necessary functions. Therefore, employing domains and domain interactions gives a better view of the protein interactions and functions. We developed novel strategy for local network alignment, DONA. DONA maps proteins into their domains and uses DDIs to improve the network alignment. We developed novel strategy for constructing an alignment graph and then uses this graph to discover the conserved sub-networks. DONA shows better performance in terms of the overlap with known protein complexes with higher precision and recall rates than existing methods. The result shows better semantic similarity computed with respect to both the biological process and the molecular function of the aligned sub-networks.

microRNA target, Machine learning, network alignment, protein complex.