Gene Co-expression Network Analysis to Understand the Progression of Rift Valley Fever in Bos Taurus.

Abstract

Rift Valley Fever (RVF) is a fatal disease caused by the Rift Valley Fever Virus (RVFV) that affects both humans and domestic animals. The disease is mainly transmitted by the Aedes and Culex mosquito species. Primarily, RVF disease infects domestic animals such as cattle, goats and sheep, resulting in varied clinical outcomes including morbidity, massive storm abortions and high rates of neonatal mortality. The occurrence of RVF is closely linked with above-average rainfall which provide a conducive environment for mosquitoes to breed, multiply and transmit the virus to animals. Human infections result in a spectrum of symptoms ranging from being asymptomatic to more serious complications such as miscarriages in pregnant women. Although several studies aimed at deciphering the pathogenesis of RVF have been conducted, to our knowledge, none has investigated gene co-expression networks to determine putative gene drivers of RVF pathogenesis. This study used a systems biology approach to construct of a Bos taurus gene co-expression network and identified functionally correlated gene clusters (modules). Moreover, consensus regulatory motifs of enriched gene clusters have been identified. Analysis of publicly available Bos taurus RNA-Seq data revealed thirty-three (33) gene clusters, with nine (9) being enriched for gene ontology terms associated with RVF pathogenesis. Out of the nine enriched modules, two (red and turquoise) modules were significantly enriched. The red module was enriched for terms such as calcineurin-NFAT signaling cascade, and ubiquitin-dependent protein catabolic process while the turquoise module was enriched for terms such as dendrite, G protein-coupled receptor activity, response to stimuli, and xenobiotic metabolic processes. The constructed gene co-expression network has uncovered functionally related genes, intramodular hub genes, and immunity genes potentially underpinning RVF pathogenesis. The putative regulatory motifs identified in this study can plausibly be targeted for RVF drug and vaccine development.