Precise mycobacterial species and subspecies identification using the PEP-TORCH peptidome algorithm

Abstract Mycobacterial infections pose a significant global health concern, requiring precise identification for effective treatment. However, diagnosing them is challenging due to inaccurate identifications and prolonged times. In this study, we aimed to develop a novel peptidome-based method using...

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Main Authors: Duran Bao, Sudipa Maity, Lingpeng Zhan, Seungyeon Seo, Qingbo Shu, Christopher J Lyon, Bo Ning, Adrian Zelazny, Tony Y Hu, Jia Fan
Format: Article
Language:English
Published: Springer Nature 2025-03-01
Series:EMBO Molecular Medicine
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Online Access:https://doi.org/10.1038/s44321-025-00207-5
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Summary:Abstract Mycobacterial infections pose a significant global health concern, requiring precise identification for effective treatment. However, diagnosing them is challenging due to inaccurate identifications and prolonged times. In this study, we aimed to develop a novel peptidome-based method using mycobacterial growth indicator tube (MGIT) cultures for faster and more accurate identification. We created the PEPtide Taxonomy/ORganism CHecking (PEP-TORCH), an algorithm that analyzes tryptic peptides identified by mass spectrometry to diagnose species and subspecies with predominance scores. PEP-TORCH demonstrated 100% accuracy in identifying mycobacterial species, subspecies, and co-infections in 81 individuals suspected of mycobacterial infections, eliminating the need for a sub-solid culture procedure, the gold standard in clinical practice. A notable strength of PEP-TORCH is its ability to provide information on species and subspecies simultaneously, a process conventionally achieved sequentially. This capability significantly expedites pathogen identification. Furthermore, a targeted proteomics method was validated in 63 clinical samples using the taxa-specific peptides selected by PEP-TORCH, making them suitable as biomarkers in more clinically friendly settings. This comprehensive identification approach holds promise for streamlining treatment strategies in clinical practice.
ISSN:1757-4684