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

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posted on 2023-06-09, 22:51 authored by Lu Lu, RanLei Wei, Sanjib Bhakta, Simon WaddellSimon Waddell, Ester Boix
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.

History

Publication status

  • Published

File Version

  • Published version

Journal

Antibiotics

ISSN

2079-6382

Publisher

MDPI

Issue

2

Volume

10

Page range

1-16

Article number

a97

Department affiliated with

  • Global Health and Infection Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2021-01-22

First Open Access (FOA) Date

2021-01-22

First Compliant Deposit (FCD) Date

2021-01-22

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