Ebola-Associated Genes in the Human Genome: Implications for Novel Targets

Abstract

Ebola Virus Disease (EVD) is a major healthcare challenge facing the globe today and if left unchecked could become a pandemic. A limited knowledgebase exists about the Ebola virus with no U.S. Federal Drug Agency (FDA) approved drugs. Ebola-specific proteins, antibodies and vaccines are being explored currently for therapy. In an attempt to first develop an understanding of the human proteins involved in the EVD and potentially create a pipeline of targets for evaluation, the human genome was mined for EVD association using 1) genetic association, 2) disease-oriented knowledge database text mining, 3) transcriptome-based Meta Analysis and 4) pathway enrichment analysis. Forty-five human proteins (29 known proteins and 16 novel previously uncharacterized proteins) were identified which were associated with EVD. Mining the proteomic expression databases revealed the detection of these 45 proteins in diverse body fluids. Detailed bioinformatics and proteomic analyses of these EVD associated proteins shed light on pathways, nature and class of the proteins and their association with diverse diseases including other infectious diseases. Mining the drug banks for association with the 45 genes reveals putative drugs including anti-neoplastics, anti-inflammatory drugs, leukotrienes, interferons, anticoagulants, nucleoside analogues, retinoic acid and statins to add to the currently meager options for therapy and supportive care. Putative targets of interest include a chemokine (C-C motif) ligand 8 (CCL8), enzymes (indoleamine 2,3-dioxygenase 1|IDO1, cytochrome c oxidase| COA6) and Short-chain dehydrogenase/reductase, SDR) and members of the receptor family, killer cell immunoglobulin-like receptor, cytoplasmic tail (KIR). Using knockout technology, the 45 proteins identified in this study can be rapidly verified for therapeutic potential. The association of these proteins with other diseases potentially expands the scope to diverse use. The results presented in this study provide a further example of harnessing the human genome to identify disease relevant proteins for subsequent research and development.