Genetic Profiling and Comorbidities of Zika Infection
Background: The difficulty in distinguishing infection by Zika virus (ZIKV) from other flaviviruses is a global health concern, particularly given the high risk of neurologic complications (including Guillain-Barre syndrome [GBS]) with ZIKV infection. Methods: We developed quantitative frameworks to compare and explore infectome, diseasome, and comorbidity of ZIKV infections. We analyzed gene expression microarray and RNA-Seq data from ZIKV, West Nile fever (WNF), chikungunya, dengue, yellow fever, Japanese encephalitis virus, GBS, and control datasets. Using neighborhood-based benchmarking and multilayer network topology, we constructed relationship networks based on the Online Mendelian Inheritance in Man database and our identified significant genes. Results: ZIKV infections showed dysregulation in expression of 929 genes. Forty-seven genes were highly expressed in both ZIKV and dengue infections. However, ZIKV shared <15 significant transcripts with other flavivirus infections. Notably, dysregulation of MAFB and SELENBP1 was common to ZIKV, dengue, and GBS infection; ATF5, TNFAIP3, and BAMB1 were common to ZIKV, dengue, and WNF; and NAMPT and PMAlP1 were common to ZIKV, GBS, and WNF. Phylogenetic, ontologic, and pathway analyses showed that ZIKV infection most resembles dengue fever. Conclusions: We have developed methodologies to investigate disease mechanisms and predictions for infectome, diseasome, and comorbidities quantitatively, and identified particular similarities between ZIKV and dengue infections.
|ISBN||1537-6613 (Electronic) 0022-1899 (Linking)|
|Authors||Moni, M. A.; Lio, P.|
|Responsible Garvan Author|
|Publisher Name||JOURNAL OF INFECTIOUS DISEASES|
|URL link to publisher's version||https://www.ncbi.nlm.nih.gov/pubmed/28934431|