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pmid:38890657

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

Yang Yu · Jie Hua · Liang Chen

BMC pediatrics · 2024 doi:10.1186/s12887-024-04881-1

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Autophagy-related molecular clusters identified as indicators for distinguishing active and latent TB infection in pediatric patients.
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10.1186/s12887-024-04881-1
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Yang Yu
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Jie Hua
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Liang Chen
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BMC pediatrics
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2024
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.
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Publicly available datasets were analyzed in this study. These data can be found in GSE37250 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE37250), GSE19491 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE19491), GSE28623 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE28623).
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Publicly available datasets were analyzed in this study. These data can be found in GSE37250 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE37250), GSE19491 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE19491), GSE28623 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE28623).
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The random forest model achieved the best training-set discrimination, with an AUC of 0.950, and the seven-gene model achieved an AUC of 0.888 in the external validation dataset.
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In comparison to GLM (AUC = 0.707) and SVM (AUC = 0.933), the RF model’s area AUC peaked at 0.950 (Fig. 7e).
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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.\nMETHODS: 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).\nRESULTS: 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.\nCONCLUSIONS: In summary, according to the present investigation, autophagy and the immunopathology of TB might be correlated. 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