Contribution of MALDI‐TOF mass spectrometry and machine learning including deep learning techniques for the detection of virulence factors of Clostridioides difficile strains

Abstract Clostridioides difficile (CD) infections are defined by toxins A (TcdA) and B (TcdB) along with the binary toxin (CDT). The emergence of the ‘hypervirulent’ (Hv) strain PR 027, along with PR 176 and 181, two decades ago, reshaped CD infection epidemiology in Europe. This study assessed MALD...

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Published in:Microbial Biotechnology
Main Authors: Alexandre Godmer, Quentin Giai Gianetto, Killian Le Neindre, Valentine Latapy, Mathilda Bastide, Muriel Ehmig, Valérie Lalande, Nicolas Veziris, Alexandra Aubry, Frédéric Barbut, Catherine Eckert
Format: Article
Language:English
Published: Wiley 2024-06-01
Online Access:https://doi.org/10.1111/1751-7915.14478
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author Alexandre Godmer
Quentin Giai Gianetto
Killian Le Neindre
Valentine Latapy
Mathilda Bastide
Muriel Ehmig
Valérie Lalande
Nicolas Veziris
Alexandra Aubry
Frédéric Barbut
Catherine Eckert
author_facet Alexandre Godmer
Quentin Giai Gianetto
Killian Le Neindre
Valentine Latapy
Mathilda Bastide
Muriel Ehmig
Valérie Lalande
Nicolas Veziris
Alexandra Aubry
Frédéric Barbut
Catherine Eckert
author_sort Alexandre Godmer
collection DOAJ
container_title Microbial Biotechnology
description Abstract Clostridioides difficile (CD) infections are defined by toxins A (TcdA) and B (TcdB) along with the binary toxin (CDT). The emergence of the ‘hypervirulent’ (Hv) strain PR 027, along with PR 176 and 181, two decades ago, reshaped CD infection epidemiology in Europe. This study assessed MALDI‐TOF mass spectrometry (MALDI‐TOF MS) combined with machine learning (ML) and Deep Learning (DL) to identify toxigenic strains (producing TcdA, TcdB with or without CDT) and Hv strains. In total, 201 CD strains were analysed, comprising 151 toxigenic (24 ToxA+B+CDT+, 22 ToxA+B+CDT+ Hv+ and 105 ToxA+B+CDT−) and 50 non‐toxigenic (ToxA−B−) strains. The DL‐based classifier exhibited a 0.95 negative predictive value for excluding ToxA−B− strains, showcasing accuracy in identifying this strain category. Sensitivity in correctly identifying ToxA+B+CDT− strains ranged from 0.68 to 0.91. Additionally, all classifiers consistently demonstrated high specificity (>0.96) in detecting ToxA+B+CDT+ strains. The classifiers' performances for Hv strain detection were linked to high specificity (≥0.96). This study highlights MALDI‐TOF MS enhanced by ML techniques as a rapid and cost‐effective tool for identifying CD strain virulence factors. Our results brought a proof‐of‐concept concerning the ability of MALDI‐TOF MS coupled with ML techniques to detect virulence factor and potentially improve the outbreak's management.
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spelling doaj-art-e86b24d938164ff0bcc6ee30a3965d482025-08-19T23:13:29ZengWileyMicrobial Biotechnology1751-79152024-06-01176n/an/a10.1111/1751-7915.14478Contribution of MALDI‐TOF mass spectrometry and machine learning including deep learning techniques for the detection of virulence factors of Clostridioides difficile strainsAlexandre Godmer0Quentin Giai Gianetto1Killian Le Neindre2Valentine Latapy3Mathilda Bastide4Muriel Ehmig5Valérie Lalande6Nicolas Veziris7Alexandra Aubry8Frédéric Barbut9Catherine Eckert10U1135, Centre d'Immunologie et Des Maladies Infectieuses (Cimi‐Paris) Sorbonne Université Paris FranceInstitut Pasteur Université Paris Cité, Bioinformatics and Biostatistics HUB Paris FranceAP‐HP, Sorbonne Université (Assistance Publique Hôpitaux de Paris), National Reference Laboratory for Clostridioides Difficile Paris FranceDépartement de Bactériologie AP‐HP, Sorbonne Université (Assistance Publique Hôpitaux de Paris), Groupe Hospitalier Universitaire, Sorbonne Université, Hôpital, Saint‐Antoine Paris FranceDépartement de Bactériologie AP‐HP, Sorbonne Université (Assistance Publique Hôpitaux de Paris), Groupe Hospitalier Universitaire, Sorbonne Université, Hôpital, Saint‐Antoine Paris FranceAP‐HP, Sorbonne Université (Assistance Publique Hôpitaux de Paris), National Reference Laboratory for Clostridioides Difficile Paris FranceDépartement de Bactériologie AP‐HP, Sorbonne Université (Assistance Publique Hôpitaux de Paris), Groupe Hospitalier Universitaire, Sorbonne Université, Hôpital, Saint‐Antoine Paris FranceU1135, Centre d'Immunologie et Des Maladies Infectieuses (Cimi‐Paris) Sorbonne Université Paris FranceU1135, Centre d'Immunologie et Des Maladies Infectieuses (Cimi‐Paris) Sorbonne Université Paris FranceAP‐HP, Sorbonne Université (Assistance Publique Hôpitaux de Paris), National Reference Laboratory for Clostridioides Difficile Paris FranceU1135, Centre d'Immunologie et Des Maladies Infectieuses (Cimi‐Paris) Sorbonne Université Paris FranceAbstract Clostridioides difficile (CD) infections are defined by toxins A (TcdA) and B (TcdB) along with the binary toxin (CDT). The emergence of the ‘hypervirulent’ (Hv) strain PR 027, along with PR 176 and 181, two decades ago, reshaped CD infection epidemiology in Europe. This study assessed MALDI‐TOF mass spectrometry (MALDI‐TOF MS) combined with machine learning (ML) and Deep Learning (DL) to identify toxigenic strains (producing TcdA, TcdB with or without CDT) and Hv strains. In total, 201 CD strains were analysed, comprising 151 toxigenic (24 ToxA+B+CDT+, 22 ToxA+B+CDT+ Hv+ and 105 ToxA+B+CDT−) and 50 non‐toxigenic (ToxA−B−) strains. The DL‐based classifier exhibited a 0.95 negative predictive value for excluding ToxA−B− strains, showcasing accuracy in identifying this strain category. Sensitivity in correctly identifying ToxA+B+CDT− strains ranged from 0.68 to 0.91. Additionally, all classifiers consistently demonstrated high specificity (>0.96) in detecting ToxA+B+CDT+ strains. The classifiers' performances for Hv strain detection were linked to high specificity (≥0.96). This study highlights MALDI‐TOF MS enhanced by ML techniques as a rapid and cost‐effective tool for identifying CD strain virulence factors. Our results brought a proof‐of‐concept concerning the ability of MALDI‐TOF MS coupled with ML techniques to detect virulence factor and potentially improve the outbreak's management.https://doi.org/10.1111/1751-7915.14478
spellingShingle Alexandre Godmer
Quentin Giai Gianetto
Killian Le Neindre
Valentine Latapy
Mathilda Bastide
Muriel Ehmig
Valérie Lalande
Nicolas Veziris
Alexandra Aubry
Frédéric Barbut
Catherine Eckert
Contribution of MALDI‐TOF mass spectrometry and machine learning including deep learning techniques for the detection of virulence factors of Clostridioides difficile strains
title Contribution of MALDI‐TOF mass spectrometry and machine learning including deep learning techniques for the detection of virulence factors of Clostridioides difficile strains
title_full Contribution of MALDI‐TOF mass spectrometry and machine learning including deep learning techniques for the detection of virulence factors of Clostridioides difficile strains
title_fullStr Contribution of MALDI‐TOF mass spectrometry and machine learning including deep learning techniques for the detection of virulence factors of Clostridioides difficile strains
title_full_unstemmed Contribution of MALDI‐TOF mass spectrometry and machine learning including deep learning techniques for the detection of virulence factors of Clostridioides difficile strains
title_short Contribution of MALDI‐TOF mass spectrometry and machine learning including deep learning techniques for the detection of virulence factors of Clostridioides difficile strains
title_sort contribution of maldi tof mass spectrometry and machine learning including deep learning techniques for the detection of virulence factors of clostridioides difficile strains
url https://doi.org/10.1111/1751-7915.14478
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