Predicting Disease-related Associations by Heterogeneous Network Embedding

Elucidating biological mechanisms underlying complex diseases is an important goal in biomedical research. Recent advances in biological technology have enabled the generation of massive volume of data in genomics, transcriptomics, proteomics, epigenomics, metagenomics, metabolomics, nutriomics, etc., leading to the emergence of systems biology approach to investigating complex diseases. However, most of the data remain underutilized after their initial acquisition and analysis. There is a growing gap between the generation of the multifaceted data and our ability to integrate and analyze them. Inspired by the observation that many of the aforementioned data can be represented by networks, we propose a network-based model to encapsulate the rich information provided in each database and to connect across different databases. We integrate several public databases to construct a heterogeneous network in which nodes are entities such as genes, miRNAs, diseases, and edges represent known relationships between them. One fundamental challenge is how to perform meaningful analysis on such network, overcoming the intrinsic heterogeneity. We propose a network embedding method to learn a low-dimensional vector space that best preserves the known relationships between entities. Based on the learned vector representations, entities that are close to each other but currently do not have known direct connections, are likely to have an association and therefore are good candidates for future investigation. In the experiments, we construct a heterogeneous network of genes, miRNAs and diseases using data from six public databases. To evaluate the performance of the proposed method, we predict disease-gene and disease-miRNA associations. Comparison of our novel method with several state-of-the-art methods clearly demonstrates the advantage of our method, as it is the only one that takes full advantage of the rich contextual information provided by the heterogeneous network. The encouraging results suggest that our method can provide help in identifying new hypotheses to guide future research.