Meta-Analysis of Peripheral Blood Transcriptome Datasets Reveals a Biomarker Panel for Tuberculosis in Patients Infected With HIV

Abstract

Biomarkers are critical for rapid diagnosis of tuberculosis (TB) and could benefit patients with AIDS where diagnosis of TB co-infection is challenging. Meta-analysis is an approach to combine the results of the studies with standard statistical method by weighting each study with different sample size. This study aimed to use meta-analysis to integrate transcriptome datasets from different studies and screen for TB biomarkers in patients who were HIV-positive. Five datasets were subjected to meta-analysis on whole-blood transcriptomes from 640 patients infected with HIV. A total of 293 differentially expressed genes (DEGs) were identified as significant (P<0.0001) using the random effective model to integrate the statistical results from each study. DEGs were enriched in biological processes related to TB, such as “Type I interferon signaling” and “stimulatory C-type lectin receptor signaling”. Eighteen DEGs had at least a two-fold change in expression between patients infected with HIV who were TB-positive and those who were TB-negative. GBP4, SERPING1, ATF3 and CDKBN3 were selected as a biomarker panel to perform multivariable logistic regression analysis on TB status and relative gene expression levels. The biomarker panel showed excellent accuracy (AUC>0.90 for HIV+TB) in clinical trial and suggests that meta-analysis is an efficient method to integrate transcriptome datasets from different studies.

Diagnosis of pulmonary tuberculosis via identification of core genes and pathways utilizing blood transcriptional signatures: a multicohort analysis

“…The latest study used meta-analysis to integrate transcriptome datasets from different studies and screen for TB biomarkers in patients who were HIV-positive [ 15 ]. In our study, we will analyse data for PTB while eliminating any potential interference from HIV by using HIV-negative patients only.…”

Differential Expression of lncRNAs in HIV Patients with TB and HIV-TB with Anti-Retroviral Treatment

“…A challenging issue in HIV-TB coinfection is the atypical presentation of TB [ 40 ]. While the conventional sputum-based detection of TB is of limited scope in these patients and often leads to false negativity [ 41 ], interferon gamma (IFN-γ)-based assays, though specific [ 42 ], are more expensive. Thus, several studies have applied transcriptomics, particularly the altered or differentially expressed protein-coding genes between HIV and HIV-TB patients, to identify biological markers for TB in HIV patients [ 43 , 44 ].…”

In-depth systems biological evaluation of bovine alveolar macrophages suggests novel insights into molecular mechanisms underlying Mycobacterium bovis infection

“…Several hub-central TFs, including ATF3 ( Chen Y. et al, 2021 ), FOSB ( Green et al, 2010 ), HIF1A ( Li F. et al, 2020 ), and IRF1 ( Pathak et al, 2007 ) were also identified that played a key immunoregulatory role in the biological behavior of the pink module. For example, HIF1A hub-central TF is a master transcriptional regulator and an important factors in regulating gene expression in response to hypoxia ( Cimmino et al, 2019 ).…”