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In silico analysis of autoimmune diseases and genetic relationships to vaccination against infectious diseases

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  • In silico analysis of autoimmune diseases and genetic relationships to vaccination against infectious diseases

    In silico analysis of autoimmune diseases and genetic relationships to vaccination against infectious diseases

    Peter B McGarvey12*, Baris E Suzek126, James N Baraniuk3, Shruti Rao1, Brian Conkright1, Samir Lababidi4, Andrea Sutherland45, Richard Forshee4 and Subha Madhavan1
    Author Affiliations
    1 Innovation Center for Biomedical Informatics, Georgetown University Medical Center, 2115 Wisconsin Ave NW, Suite 110, Washington 20007, DC, USA
    2 Protein Information Resource, Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, 3300 Whitehaven Street NW, Suite 1200, Washington 20007, DC, USA
    3 Division of Rheumatology, Immunology and Allergy, Department of Medicine, Georgetown University Medical Center, 3800 Reservoir Road, NW, Washington 20007, DC, USA
    4 Office of Biostatistics and Epidemiology, Center for Biologics Evaluation and Research, US Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring 20993, MD, USA
    5 Department of International Health, Johns Hopkins School of Public Health, 615 North Wolfe Street, Baltimore 21205, MD, USA
    6 Department of Computer Engineering, Muğla Sıtkı Ko?man University, Muğla, Turkey

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    BMC Immunology 2014, 15:61 doi:10.1186/s12865-014-0061-0
    The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1471-2172/15/61
    Received: 7 November 2014
    Accepted: 1 December 2014
    Published: 9 December 2014
    ? 2014 McGarvey et al.; licensee BioMed Ltd.
    This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.


    Abstract

    Background

    Near universal administration of vaccines mandates intense pharmacovigilance for vaccine safety and a stringently low tolerance for adverse events. Reports of autoimmune diseases (AID) following vaccination have been challenging to evaluate given the high rates of vaccination, background incidence of autoimmunity, and low incidence and variable times for onset of AID after vaccinations. In order to identify biologically plausible pathways to adverse autoimmune events of vaccine-related AID, we used a systems biology approach to create a matrix of innate and adaptive immune mechanisms active in specific diseases, responses to vaccine antigens, adjuvants, preservatives and stabilizers, for the most common vaccine-associated AID found in the Vaccine Adverse Event Reporting System.
    Results

    This report focuses on Guillain-Barre Syndrome (GBS), Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE), and Idiopathic (or immune) Thrombocytopenic Purpura (ITP). Multiple curated databases and automated text mining of PubMed literature identified 667 genes associated with RA, 448 with SLE, 49 with ITP and 73 with GBS. While all data sources provided valuable and unique gene associations, text mining using natural language processing (NLP) algorithms provided the most information but required curation to remove incorrect associations. Six genes were associated with all four AIDs. Thirty-three pathways were shared by the four AIDs. Classification of genes into twelve immune system related categories identified more ?Th17 T-cell subtype? genes in RA than the other AIDs, and more ?Chemokine plus Receptors? genes associated with RA than SLE. Gene networks were visualized and clustered into interconnected modules with specific gene clusters for each AID, including one in RA with ten C-X-C motif chemokines. The intersection of genes associated with GBS, GBS peptide auto-antigens, influenza A infection, and influenza vaccination created a subnetwork of genes that inferred a possible role for the MAPK signaling pathway in influenza vaccine related GBS.
    Conclusions

    Results showing unique and common gene sets, pathways, immune system categories and functional clusters of genes in four autoimmune diseases suggest it is possible to develop molecular classifications of autoimmune and inflammatory events. Combining this information with cellular and other disease responses should greatly aid in the assessment of potential immune-mediated adverse events following vaccination.
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