Weighted gene co-expression network analysis identifies key modules and hub genes associated with mycobacterial infection of human macrophages

Lu, Lu, Wei, RanLei, Bhakta, Sanjib, Waddell, Simon and Boix, Ester (2021) Weighted gene co-expression network analysis identifies key modules and hub genes associated with mycobacterial infection of human macrophages. Antibiotics, 10 (2). a97 1-16. ISSN 2079-6382

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Abstract

Tuberculosis (TB) is still a leading cause of death worldwide. Treatments remain unsatisfactory due to an incomplete understanding of the underlying host–pathogen interactions during infection. In the present study, weighted gene co-expression network analysis (WGCNA) was conducted to identify key macrophage modules and hub genes associated with mycobacterial infection. WGCNA was performed combining our own transcriptomic results using Mycobacterium aurum-infected human monocytic macrophages (THP1) with publicly accessible datasets obtained from three types of macrophages infected with seven different mycobacterial strains in various one-to-one combinations. A hierarchical clustering tree of 11,533 genes was built from 198 samples, and 47 distinct modules were revealed. We identified a module, consisting of 226 genes, which represented the common response of host macrophages to different mycobacterial infections that showed significant enrichment in innate immune stimulation, bacterial pattern recognition, and leukocyte chemotaxis. Moreover, by network analysis applied to the 74 genes with the best correlation with mycobacteria infection, we identified the top 10 hub-connecting genes: NAMPT, IRAK2, SOCS3, PTGS2, CCL20, IL1B, ZC3H12A, ABTB2, GFPT2, and ELOVL7. Interestingly, apart from the well-known Toll-like receptor and inflammation-associated genes, other genes may serve as novel TB diagnosis markers and potential therapeutic targets.

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Global Health and Infection
SWORD Depositor: Mx Elements Account
Depositing User: Mx Elements Account
Date Deposited: 22 Jan 2021 08:36
Last Modified: 22 Jan 2021 08:45
URI: http://sro.sussex.ac.uk/id/eprint/96623

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