A novel subnetwork based analysis reveals shared pathways in T-cell mediated autoimmunity

Hdl Handle:
http://hdl.handle.net/10675.2/605888
Title:
A novel subnetwork based analysis reveals shared pathways in T-cell mediated autoimmunity
Authors:
Pabla, Simarjot Singh
Abstract:
Thymocyte auto-reactivity is an underlying theme of several autoimmune disorders. The precise role of auto-reactive T cells in the initiation and subsequent progression of autoimmune disorders has been studied extensively. However, these disease specific studies ignore pathways that may be in common to several T cell mediated autoimmune pathologies. This can be attributed in part to the shortcomings of traditional gene list based gene expression studies. Here we report a novel method to identify unifying gene expression changes in several autoimmune diseases. In order to uncover pathologically important pathways common to T-cell mediated autoimmune disorders, we used human gene expression data from Multiple Sclerosis, Rheumatoid Arthritis, Juvenile Idiopathic Arthritis and Sjögren’s syndrome. Unlike traditional gene expression analysis, we used jointly active connected subnetwork enrichment to identify subnetworks for each disorder, followed by topological network alignment, which led to identification of shared pathways. We report four pathways shared in these disorders, which include DNA damage response, gonadotropin, innate and adaptive immunity pathways. Importantly, our method did not reveal any common pathways in unrelated diseases. In order to experimentally validate our findings, RNA sequencing of mRNA isolated from salivary glands excised from a murine model of Sjögren’s syndrome was performed. High similarities were observed between Human T-cell mediated autoimmune disorders and Sjögren’s murine model. Collectively, these studies have identified a shared landscape of pathologically significant pathways, including DNA damage response, gonadotropin, innate and adaptive immunity in autoimmune disorders and provide a new methodology to identify common alterations in diseases with similar underlying etiologies.
Affiliation:
Center for Biotechnology and Genomic Medicine
Issue Date:
Mar-2016
URI:
http://hdl.handle.net/10675.2/605888
Type:
Dissertation
Appears in Collections:
Theses and Dissertations; Center for Biotechnology and Genomic Medicine Theses and Dissertations

Full metadata record

DC FieldValue Language
dc.contributor.authorPabla, Simarjot Singhen
dc.date.accessioned2016-04-19T13:37:00Zen
dc.date.available2016-04-19T13:37:00Zen
dc.date.issued2016-03en
dc.identifier.urihttp://hdl.handle.net/10675.2/605888en
dc.description.abstractThymocyte auto-reactivity is an underlying theme of several autoimmune disorders. The precise role of auto-reactive T cells in the initiation and subsequent progression of autoimmune disorders has been studied extensively. However, these disease specific studies ignore pathways that may be in common to several T cell mediated autoimmune pathologies. This can be attributed in part to the shortcomings of traditional gene list based gene expression studies. Here we report a novel method to identify unifying gene expression changes in several autoimmune diseases. In order to uncover pathologically important pathways common to T-cell mediated autoimmune disorders, we used human gene expression data from Multiple Sclerosis, Rheumatoid Arthritis, Juvenile Idiopathic Arthritis and Sjögren’s syndrome. Unlike traditional gene expression analysis, we used jointly active connected subnetwork enrichment to identify subnetworks for each disorder, followed by topological network alignment, which led to identification of shared pathways. We report four pathways shared in these disorders, which include DNA damage response, gonadotropin, innate and adaptive immunity pathways. Importantly, our method did not reveal any common pathways in unrelated diseases. In order to experimentally validate our findings, RNA sequencing of mRNA isolated from salivary glands excised from a murine model of Sjögren’s syndrome was performed. High similarities were observed between Human T-cell mediated autoimmune disorders and Sjögren’s murine model. Collectively, these studies have identified a shared landscape of pathologically significant pathways, including DNA damage response, gonadotropin, innate and adaptive immunity in autoimmune disorders and provide a new methodology to identify common alterations in diseases with similar underlying etiologies.en
dc.rightsCopyright protected. Unauthorized reproduction or use beyond the exceptions granted by the Fair Use clause of U.S. Copyright law may violate federal law.en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectSjogren's Syndromeen
dc.subjectMultiple Sclerosisen
dc.subjectArthritis, Rheumatoiden
dc.subjectArthritis, Juvenileen
dc.titleA novel subnetwork based analysis reveals shared pathways in T-cell mediated autoimmunityen
dc.typeDissertationen
dc.contributor.departmentCenter for Biotechnology and Genomic Medicineen
dc.description.advisorMcIndoe, Richarden
dc.description.committeePacholczyk, Rafal; Sharma, Ashok; Xu, Hongyan; Shi, Huidongen
dc.description.degreeDoctor of Philosophy with a Major in Genomic Medicineen
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