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Identifying mitochondria-related signatures for tuberculosis diagnosis through machine learning on single-cell
Xianyi Zhang1, Kehong Zhang2, Yu Wang3
1The Baoan People's Hospital of Shenzhen, The Second Affiliated Hospital of Shenzhen University, Shenzhen University, Shenzhen, 518000, China.
Microbial Pathogenesis
|April 12, 2026
Summary
Researchers identified three mitochondria-related genes (STAT2, CASP1, COX7B) as biomarkers for diagnosing active tuberculosis disease (TBD). This blood-based test offers a promising, non-sputum alternative for early detection and treatment initiation.
Area of Science:
- Biomolecular analysis and diagnostics
- Genomics and transcriptomics
- Infectious disease research
Background:
- Tuberculosis (TB) causes significant mortality, with early diagnosis critical for control.
- Current diagnostic methods often rely on sputum, delaying detection and treatment.
- Mitochondrial dysregulation is implicated in Mycobacterium tuberculosis (MTB) evasion.
Purpose of the Study:
- To identify mitochondria-related gene signatures as potential biomarkers for active tuberculosis disease (TBD).
- To develop and validate a non-sputum-based diagnostic model for TBD using blood samples.
Main Methods:
- Integrated microarray and single-cell RNA sequencing data from active TB, latent TB, and healthy controls.
- Identified ten mitochondria-related differentially expressed genes (MitoDEGs) in monocytic cells.
- Utilized LASSO and SVM-RFE algorithms to select three hub markers (STAT2, CASP1, COX7B) for a diagnostic model.
Main Results:
- A three-MitoDEG (STAT2, CASP1, COX7B) blood-based diagnostic model was constructed.
- The model demonstrated robust diagnostic performance across training, validation, and independent testing sets (AUCs ranging from 0.852 to 0.993).
- An independent clinical cohort confirmed the model's efficacy in discriminating TBD from non-TB controls (AUC = 0.909).
Conclusions:
- A novel three-MitoDEG signature shows significant potential as a blood-based diagnostic tool for TBD.
- This non-sputum approach offers a scalable alternative for TB triage, especially in resource-limited settings.
- Further validation could lead to improved early diagnosis and management of tuberculosis.
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