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

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 infect...

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Autores principales:	Jacqueline U. McDonald, Myrsini Kaforou, Simon Clare, Christine Hale, Maria Ivanova, Derek Huntley, Marcus Dorner, Victoria J. Wright, Michael Levin, Federico Martinon-Torres, Jethro A. Herberg, John S. Tregoning
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	host response immunity respiratory syncytial virus viral immunity Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/c043515a01fd43c196b5287f8e06adfe
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spelling	oai:doaj.org-article:c043515a01fd43c196b5287f8e06adfe2021-12-02T18:39:34ZA Simple Screening Approach To Prioritize Genes for Functional Analysis Identifies a Role for Interferon Regulatory Factor 7 in the Control of Respiratory Syncytial Virus Disease10.1128/mSystems.00051-162379-5077https://doaj.org/article/c043515a01fd43c196b5287f8e06adfe2016-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00051-16https://doaj.org/toc/2379-5077ABSTRACT 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. IMPORTANCE Making the most of “big data” is one of the core challenges of current biology. There is a large array of heterogeneous data sets of host gene responses to infection, but these data sets do not inform us about gene function and require specialized skill sets and training for their utilization. Here we describe an approach that combines and simplifies these data sets, distilling this information into a single list of genes commonly upregulated in response to infection with RSV as a model pathogen. Many of the genes on the list have unknown functions in RSV disease. We validated the gene list with new clinical, in vitro, and in vivo data. This approach allows the rapid selection of genes of interest for further, more-detailed studies, thus reducing time and costs. Furthermore, the approach is simple to use and widely applicable to a range of diseases.Jacqueline U. McDonaldMyrsini KaforouSimon ClareChristine HaleMaria IvanovaDerek HuntleyMarcus DornerVictoria J. WrightMichael LevinFederico Martinon-TorresJethro A. HerbergJohn S. TregoningAmerican Society for Microbiologyarticlehost responseimmunityrespiratory syncytial virusviral immunityMicrobiologyQR1-502ENmSystems, Vol 1, Iss 3 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	host response immunity respiratory syncytial virus viral immunity Microbiology QR1-502
spellingShingle	host response immunity respiratory syncytial virus viral immunity Microbiology QR1-502 Jacqueline U. McDonald Myrsini Kaforou Simon Clare Christine Hale Maria Ivanova Derek Huntley Marcus Dorner Victoria J. Wright Michael Levin Federico Martinon-Torres Jethro A. Herberg John S. Tregoning 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
description	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. IMPORTANCE Making the most of “big data” is one of the core challenges of current biology. There is a large array of heterogeneous data sets of host gene responses to infection, but these data sets do not inform us about gene function and require specialized skill sets and training for their utilization. Here we describe an approach that combines and simplifies these data sets, distilling this information into a single list of genes commonly upregulated in response to infection with RSV as a model pathogen. Many of the genes on the list have unknown functions in RSV disease. We validated the gene list with new clinical, in vitro, and in vivo data. This approach allows the rapid selection of genes of interest for further, more-detailed studies, thus reducing time and costs. Furthermore, the approach is simple to use and widely applicable to a range of diseases.
format	article
author	Jacqueline U. McDonald Myrsini Kaforou Simon Clare Christine Hale Maria Ivanova Derek Huntley Marcus Dorner Victoria J. Wright Michael Levin Federico Martinon-Torres Jethro A. Herberg John S. Tregoning
author_facet	Jacqueline U. McDonald Myrsini Kaforou Simon Clare Christine Hale Maria Ivanova Derek Huntley Marcus Dorner Victoria J. Wright Michael Levin Federico Martinon-Torres Jethro A. Herberg John S. Tregoning
author_sort	Jacqueline U. McDonald
title	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
title_short	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
title_full	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
title_fullStr	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
title_full_unstemmed	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
title_sort	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
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/c043515a01fd43c196b5287f8e06adfe
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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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