Autophagy-related molecular clusters identified as indicators for distinguishing active and latent TB infection in pediatric patients

Abstract

Abstract Background Autophagy is crucial for controlling the manifestation of tuberculosis. This study intends to discover autophagy-related molecular clusters as biomarkers for discriminating between latent tuberculosis (LTBI) and active tuberculosis (ATB) in children through gene expression profile analysis. Methods The expression of autophagy modulators was examined in pediatric patients with LTBI and ATB utilizing public datasets from the Gene Expression Omnibus (GEO) collection (GSE39939 and GSE39940). Results In a training dataset (GSE39939), patients with LTBI and ATB exhibited the expression of autophagy-related genes connected with their active immune responses. Two molecular clusters associated with autophagy were identified. Compared to Cluster 1, Cluster 2 was distinguished through decreased adaptive cellular immune response and enhanced inflammatory activation, according to single-sample gene set enrichment analysis (ssGSEA). Per the study of gene set variation, Cluster 2’s differentially expressed genes (DEGs) played a role in synthesizing transfer RNA, DNA repair and recombination, and primary immunodeficiency. The peak variation efficiency, root mean square error, and area under the curve (AUC) (AUC = 0.950) were all lowered in random forest models. Finally, a seven-gene-dependent random forest profile was created utilizing the CD247, MAN1C1, FAM84B, HSZFP36, SLC16A10, DTX3, and SIRT4 genes, which performed well against the validation dataset GSE139940 (AUC = 0.888). The nomogram calibration and decision curves performed well in identifying ATB from LTBI. Conclusions In summary, according to the present investigation, autophagy and the immunopathology of TB might be correlated. Furthermore, this investigation established a compelling prediction expression profile for measuring autophagy subtype development risks, which might be employed as possible biomarkers in children to differentiate ATB from LTBI.

Keywords

• Autophagy
• Molecular cluster
• Model
• Active tuberculosis
• Latent tuberculosis
• Children