A scalable random walk with restart on heterogeneous networks with Apache Spark for ranking disease-related genes through type-II fuzzy data fusion

Abstract

One of the effective missions of biology and medical science is to find disease-related genes. Recent research uses gene/protein networks to find such genes. Due to false positive interactions in these networks, the results often are not accurate and reliable. Integrating multiple gene/protein networks could overcome this drawback, causing a network with fewer false positive interactions. The integration method plays a crucial role in the quality of the constructed network. In this paper, we integrate several sources to build a reliable heterogeneous network, i.e., a network that includes nodes of different types. Due to the different gene/protein sources, four gene-gene similarity networks are constructed first and integrated by applying the type-II fuzzy voter scheme. The resulting gene-gene network is linked to a disease-disease similarity network (as the outcome of integrating four sources) through a two-part disease-gene network. We propose a novel algorithm, namely random walk with restart on the heterogeneous network method with fuzzy fusion (RWRHN-FF). Through running RWRHN-FF over the heterogeneous network, disease-related genes are determined. Experimental results using the leave-one-out cross-validation indicate that RWRHN-FF outperforms existing methods. The proposed algorithm can be applied to find new genes for prostate, breast, gastric, and colon cancers. Since the RWRHN-FF algorithm converges slowly on large heterogeneous networks, we propose a parallel implementation of the RWRHN-FF algorithm on the Apache Spark platform for high-throughput and reliable network inference. Experiments run on heterogeneous networks of different sizes indicate faster convergence compared to other non-distributed modes of implementation.