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. 2016 Jan 11;11(1):e0146585.
doi: 10.1371/journal.pone.0146585. eCollection 2016.

Network Analysis of Human Genes Influencing Susceptibility to Mycobacterial Infections

Ettie M Lipner  1   2 , Benjamin J Garcia  1   2 , Michael Strong  1   2
Affiliations

Network Analysis of Human Genes Influencing Susceptibility to Mycobacterial Infections

Ettie M Lipner et al. PLoS One. .

Abstract

Tuberculosis and nontuberculous mycobacterial infections constitute a high burden of pulmonary disease in humans, resulting in over 1.5 million deaths per year. Building on the premise that genetic factors influence the instance, progression, and defense of infectious disease, we undertook a systems biology approach to investigate relationships among genetic factors that may play a role in increased susceptibility or control of mycobacterial infections. We combined literature and database mining with network analysis and pathway enrichment analysis to examine genes, pathways, and networks, involved in the human response to Mycobacterium tuberculosis and nontuberculous mycobacterial infections. This approach allowed us to examine functional relationships among reported genes, and to identify novel genes and enriched pathways that may play a role in mycobacterial susceptibility or control. Our findings suggest that the primary pathways and genes influencing mycobacterial infection control involve an interplay between innate and adaptive immune proteins and pathways. Signaling pathways involved in autoimmune disease were significantly enriched as revealed in our networks. Mycobacterial disease susceptibility networks were also examined within the context of gene-chemical relationships, in order to identify putative drugs and nutrients with potential beneficial immunomodulatory or anti-mycobacterial effects.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Database-derived TB and NTM-associated genes.
Fig 2
Fig 2. Union of TB and NTM gene sets: network 1.
Grey: Network identified genes; Blue: TB or NTM focus genes.
Fig 3
Fig 3. Union of TB and NTM gene sets: network 2.
Grey: Network identified genes; Blue: TB or NTM focus genes.
Fig 4
Fig 4. TB network.
Grey: Network identified genes; Blue: TB focus genes.
Fig 5
Fig 5. NTM network.
Grey: Network identified genes; Blue: NTM focus genes.
Fig 6
Fig 6. Intersection of TB and NTM gene sets.
Grey: Network identified genes; Blue: TB and NTM focus genes.
Fig 7
Fig 7. Network-identified immune-modulating chemicals.
Grey: Network identified chemicals; Blue: Network identified genes.
Fig 8
Fig 8. Network-identified nutrients.
Grey: Network identified vitamins; Blue: Network identified genes.
See this image and copyright information in PMC

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References

    1. Donoghue HD, Spigelman M, Greenblatt CL, Lev-Maor G, Bar-Gal GK, Matheson C, et al. Tuberculosis: from prehistory to Robert Koch, as revealed by ancient DNA. Lancet Infect Dis. 2004. September;4(9):584–92. - PubMed
    1. Zink AR, Grabner W, Reischl U, Wolf H, Nerlich AG. Molecular study on human tuberculosis in three geographically distinct and time delineated populations from ancient Egypt. Epidemiol Infect 2003. March;130(2):239–49. - PMC - PubMed
    1. World Health Organization. Global tuberculosis report 2014. World Health Organization; 2014.
    1. Falkinham JO. Surrounded by mycobacteria: nontuberculous mycobacteria in the human environment. J Appl Microbiol. 2009. August;107(2):356–67. 10.1111/j.1365-2672.2009.04161.x - DOI - PubMed
    1. Kennedy TP, Weber DJ. Nontuberculous mycobacteria. An underappreciated cause of geriatric lung disease. Am J Respir Crit Care Med. 1994. June;149(6):1654–8 - PubMed

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