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Gene expression profiling meta-analysis reveals novel gene signatures and pathways shared between tuberculosis and rheumatoid arthritis.

ABSTRACT: Tuberculosis (TB) is among the leading causes of death by infectious diseases. An epidemiological association between Mycobacterium tuberculosis infection and autoimmune diseases like rheumatoid arthritis (RA) has been reported but it remains unclear if there is a causal relationship, and if so, which molecular pathways and regulatory mechanisms contribute to it. Here we used a computational biology approach by global gene expression meta-analysis to identify candidate genes and pathways that may link TB and RA. Data were collected from public expression databases such as NCBI GEO. Studies were selected that analyzed mRNA-expression in whole blood or blood cell populations in human case control studies at comparable conditions. Six TB and RA datasets (41 active TB patients, 33 RA patients, and 67 healthy controls) were included in the downstream analysis. This approach allowed the identification of deregulated genes that had not been identified in the single analysis of TB or RA patients and that were co-regulated in TB and RA patients compared to healthy subjects. The genes encoding TLR5, TNFSF10/TRAIL, PPP1R16B/TIMAP, SIAH1, PIK3IP1, and IL17RA were among the genes that were most significantly deregulated in TB and RA. Pathway enrichment analysis revealed 'T cell receptor signaling pathway', 'Toll-like receptor signaling pathway,' and 'virus defense related pathways' among the pathways most strongly associated with both diseases. The identification of a common gene signature and pathways substantiates the observation of an epidemiological association of TB and RA and provides clues on the mechanistic basis of this association. Newly identified genes may be a basis for future functional and epidemiological studies.

SUBMITTER: Badr MT

PROVIDER: S-EPMC6405138 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Gene expression profiling meta-analysis reveals novel gene signatures and pathways shared between tuberculosis and rheumatoid arthritis.

Badr M T MT Häcker G G

PloS one 20190307 3

Tuberculosis (TB) is among the leading causes of death by infectious diseases. An epidemiological association between Mycobacterium tuberculosis infection and autoimmune diseases like rheumatoid arthritis (RA) has been reported but it remains unclear if there is a causal relationship, and if so, which molecular pathways and regulatory mechanisms contribute to it. Here we used a computational biology approach by global gene expression meta-analysis to identify candidate genes and pathways that ma ...[more]

PMID: 30845171

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Project description:ObjectiveTo explore the shared gene signatures and potential molecular mechanisms of polyarticular juvenile idiopathic arthritis (pJIA) and autoimmune uveitis (AU).MethodThe microarray data of pJIA and AU from the Gene Expression Omnibus (GEO) database were downloaded and analyzed. The GEO2R tool was used to identify the shared differentially expressed genes (DEGs) and genes of extracellular proteins were identified among them. Then, weighted gene co-expression network analysis (WGCNA) was used to identify the shared immune-related genes (IRGs) related to pJIA and AU. Moreover, the shared transcription factors (TFs) and microRNAs (miRNAs) in pJIA and AU were acquired by comparing data from HumanTFDB, hTFtarget, GTRD, HMDD, and miRTarBase. Finally, Metascape and g: Profiler were used to carry out function enrichment analyses of previously identified gene sets.ResultsWe found 40 up-regulated and 15 down-regulated shared DEGs via GEO2R. Then 24 shared IRGs in positivity-related modules, and 18 shared IRGs in negatively-related modules were found after WGCNA. After that, 3 shared TFs (ARID1A, SMARCC2, SON) were screened. And the constructed TFs-shared DEGs network indicates a central role of ARID1A. Furthermore, hsa-miR-146 was found important in both diseases. The gene sets enrichment analyses suggested up-regulated shared DEGs, TFs targeted shared DEGs, and IRGs positivity-correlated with both diseases mainly enriched in neutrophil degranulation process, IL-4, IL-13, and cytokine signaling pathways. The IRGs negatively correlated with pJIA and AU mainly influence functions of the natural killer cell, cytotoxicity, and glomerular mesangial cell proliferation. The down-regulated shared DEGs and TFs targeted shared DEGs did not show particular functional enrichment.ConclusionOur study fully demonstrated the flexibility and complexity of the immune system disorders involved in pJIA and AU. Neutrophil degranulation may be considered the shared pathogenic mechanism, and the roles of ARID1A and MiR-146a are worthy of further in-depth study. Other than that, the importance of periodic inspection of kidney function is also noteworthy.

Dataset Information

Gene expression profiling meta-analysis reveals novel gene signatures and pathways shared between tuberculosis and rheumatoid arthritis.

Publications

Gene expression profiling meta-analysis reveals novel gene signatures and pathways shared between tuberculosis and rheumatoid arthritis.

Similar Datasets

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