Gene co-expression network identifies critical genes, pathways and regulatory motifs mediating the progression of rift valley fever in Bostaurus

Rift Valley Fever (RVF) is a mosquito-borne viral disease caused by the Rift Valley Fever Virus. The disease is a zoonosis that largely affects domestic animals, including sheep, goats, and cattle, resulting in severe morbidity and mortality marked by massive storm abortions. To halt human and livestock deaths due to RVF, the development of efficacious vaccines and therapeutics is a compelling and urgent priority. We sought to identify potential key modules (gene clusters), hub genes, and regulatory motifs involved in the pathogenesis of RVF in Bos taurus that are amenable to inhibition. We analyzed 39 Bos taurus RNA-Seq samples using the weighted gene co-expression network analysis (WGCNA) R package and uncovered significantly enriched modules containing genes with potential pivotal roles in RVF progression. Moreover, regulatory motif analysis conducted using the Multiple Expectation Maximization for Motif Elicitation (MEME) suite identified motifs that probably modulate vital biological processes. Gene ontology terms associated with identified motifs were inferred using the GoMo human database. The gene co-expression network constructed in WGCNA using 5000 genes contained seven (7) modules, out of which four were significantly enriched for terms associated with response to viruses, response to interferon-alpha, innate immune response, and viral defense. Additionally, several biological pathways implicated in developmental processes, anatomical structure development, and multicellular organism development were identified. Regulatory motifs analysis identified short, repeated motifs whose function(s) may be amenable to disruption by novel therapeutics. Predicted functions of identified motifs include tissue development, embryonic organ development, and organ morphogenesis. We have identified several hub genes in enriched co-expressed gene modules and regulatory motifs potentially involved in the pathogenesis of RVF in B. taurus that are likely viable targets for disruption by novel therapeutics.