A Simple Screening Approach To Prioritize Genes for Functional Analysis Identifies a Role for Interferon Regulatory Factor 7 in the Control of Respiratory Syncytial Virus Disease
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Published version
Accepted version
Author(s)
Type
Journal Article
Abstract
Greater understanding of the functions of host gene products in response to infection is required. While many of these genes enable pathogen clearance, some enhance pathogen growth or contribute to disease symptoms. Many studies have profiled transcriptomic and proteomic responses to infection, generating large data sets, but selecting targets for further study is challenging. Here we propose a novel data-mining approach combining multiple heterogeneous data sets to prioritize genes for further study by using respiratory syncytial virus (RSV) infection as a model pathogen with a significant health care impact. The assumption was that the more frequently a gene is detected across multiple studies, the more important its role is. A literature search was performed to find data sets of genes and proteins that change after RSV infection. The data sets were standardized, collated into a single database, and then panned to determine which genes occurred in multiple data sets, generating a candidate gene list. This candidate gene list was validated by using both a clinical cohort and in vitro screening. We identified several genes that were frequently expressed following RSV infection with no assigned function in RSV control, including IFI27, IFIT3, IFI44L, GBP1, OAS3, IFI44, and IRF7. Drilling down into the function of these genes, we demonstrate a role in disease for the gene for interferon regulatory factor 7, which was highly ranked on the list, but not for IRF1, which was not. Thus, we have developed and validated an approach for collating published data sets into a manageable list of candidates, identifying novel targets for future analysis.
Date Issued
2016-06-28
Date Acceptance
2016-05-26
Citation
mSystems, 2016, 1 (3)
ISSN
2379-5077
Publisher
American Society for Microbiology
Journal / Book Title
mSystems
Volume
1
Issue
3
Copyright Statement
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
License URL
Sponsor
Commission of the European Communities
Grant Number
115308
Subjects
host response
immunity
respiratory syncytial virus
viral immunity
Publication Status
Published
Article Number
e00051-16