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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author Duran Bao
Sudipa Maity
Lingpeng Zhan
Seungyeon Seo
Qingbo Shu
Christopher J Lyon
Bo Ning
Adrian Zelazny
Tony Y Hu
Jia Fan
author_facet Duran Bao
Sudipa Maity
Lingpeng Zhan
Seungyeon Seo
Qingbo Shu
Christopher J Lyon
Bo Ning
Adrian Zelazny
Tony Y Hu
Jia Fan
author_sort Duran Bao
collection DOAJ
description 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.
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spelling doaj-art-6d58fab9e73249259d6ceab3eae2a1be2025-08-20T02:11:42ZengSpringer NatureEMBO Molecular Medicine1757-46842025-03-0117484186110.1038/s44321-025-00207-5Precise mycobacterial species and subspecies identification using the PEP-TORCH peptidome algorithmDuran Bao0Sudipa Maity1Lingpeng Zhan2Seungyeon Seo3Qingbo Shu4Christopher J Lyon5Bo Ning6Adrian Zelazny7Tony Y Hu8Jia Fan9Center for Cellular and Molecular Diagnostics, Tulane University School of MedicineCenter for Cellular and Molecular Diagnostics, Tulane University School of MedicineCenter for Cellular and Molecular Diagnostics, Tulane University School of MedicineDepartment of Laboratory Medicine, NIH Clinical Center, NIHCenter for Cellular and Molecular Diagnostics, Tulane University School of MedicineCenter for Cellular and Molecular Diagnostics, Tulane University School of MedicineCenter for Cellular and Molecular Diagnostics, Tulane University School of MedicineDepartment of Laboratory Medicine, NIH Clinical Center, NIHCenter for Cellular and Molecular Diagnostics, Tulane University School of MedicineCenter for Cellular and Molecular Diagnostics, Tulane University School of MedicineAbstract 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.https://doi.org/10.1038/s44321-025-00207-5AlgorithmLC-MS/MSNontuberculosis MycobacteriumPeptidomeSubspecies
spellingShingle Duran Bao
Sudipa Maity
Lingpeng Zhan
Seungyeon Seo
Qingbo Shu
Christopher J Lyon
Bo Ning
Adrian Zelazny
Tony Y Hu
Jia Fan
Precise mycobacterial species and subspecies identification using the PEP-TORCH peptidome algorithm
EMBO Molecular Medicine
Algorithm
LC-MS/MS
Nontuberculosis Mycobacterium
Peptidome
Subspecies
title Precise mycobacterial species and subspecies identification using the PEP-TORCH peptidome algorithm
title_full Precise mycobacterial species and subspecies identification using the PEP-TORCH peptidome algorithm
title_fullStr Precise mycobacterial species and subspecies identification using the PEP-TORCH peptidome algorithm
title_full_unstemmed Precise mycobacterial species and subspecies identification using the PEP-TORCH peptidome algorithm
title_short Precise mycobacterial species and subspecies identification using the PEP-TORCH peptidome algorithm
title_sort precise mycobacterial species and subspecies identification using the pep torch peptidome algorithm
topic Algorithm
LC-MS/MS
Nontuberculosis Mycobacterium
Peptidome
Subspecies
url https://doi.org/10.1038/s44321-025-00207-5
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