Gene network in pulmonary tuberculosis based on bioinformatic analysis

Lili Li,Yuan He,Zhihua Wang,Jian Lv

doi:10.1186/s12879-020-05335-6

Abstract

BackgroundPulmonary tuberculosis (PTB) is one of the serious infectious diseases worldwide; however, the gene network involved in the host response remain largely unclear.MethodsThis study integrated two cohorts profile datasets GSE34608 and GSE83456 to elucidate the potential gene network and signaling pathways in PTB. Differentially expressed genes (DEGs) were obtained for Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis using Metascape database. Protein-Protein Interaction (PPI) network of DEGs was constructed by the online database the Search Tool for the Retrieval of Interacting Genes (STRING). Modules were identified by the plug-in APP Molecular Complex Detection (MCODE) in Cytoscape. GO and KEGG pathway of Module 1 were further analyzed by STRING. Hub genes were selected for further expression validation in dataset GSE19439. The gene expression level was also investigated in the dataset GSE31348 to display the change pattern during the PTB treatment.ResultsTotally, 180 shared DEGs were identified from two datasets. Gene function and KEGG pathway enrichment revealed that DEGs mainly enriched in defense response to other organism, response to bacterium, myeloid leukocyte activation, cytokine production, etc. Seven modules were clustered based on PPI network. Module 1 contained 35 genes related to cytokine associated functions, among which 14 genes, including chemokine receptors, interferon-induced proteins and Toll-like receptors, were identified as hub genes. Expression levels of the hub genes were validated with a third dataset GSE19439. The signature of this core gene network showed significant response to Mycobacterium tuberculosis (Mtb) infection, and correlated with the gene network pattern during anti-PTB therapy.ConclusionsOur study unveils the coordination of causal genes during PTB infection, and provides a promising gene panel for PTB diagnosis. As major regulators of the host immune response to Mtb infection, the 14 hub genes are also potential molecular targets for developing PTB drugs.

Highlights

Pulmonary tuberculosis (PTB) is one of the serious infectious diseases worldwide; the gene network involved in the host response remain largely unclear
Identification of Differentially expressed genes (DEGs) Gene expression profile of GSE34608 and GSE83456 were downloaded from GEO database
PCA plots of both datasets indicated the distinction expression of control and PTB samples (Fig. 1a and b). 2214 and 1025 DEGs were identified from GSE34608 and GSE83456 datasets, respectively (Fig. 2a)

Summary

Introduction

Pulmonary tuberculosis (PTB) is one of the serious infectious diseases worldwide; the gene network involved in the host response remain largely unclear. Pulmonary tuberculosis (PTB) is one of the serious infectious diseases with high mortality in the world. PTB is caused by various strains of mycobacteria with Mycobacterium tuberculosis (Mtb) being mostly observed in human. According to the World Health Organization (WHO) report, there were 10 million new cases of PTB disease and 1.5 million deaths worldwide in 2017 (WHO, 2018). It has been estimated that one third of the world’s population are infected with Mtb as latent infections, among which 5 to 10% would develop into active tuberculosis (TB) [1, 2]. Quick diagnostic and efficient treatment are of great importance to control the spread of PTB and reduce its mortality [3, 4]. Despite accumulating evidence on the mechanism of PTB, the molecular processes and the specific gene regulations in the progression of PTB remain to be explored

Methods

Results

Conclusion