Using circulating microbial cell-free DNA to identify persistent Treponema pallidum infection in serofast syphilis patients

Summary: The question of whether serofast status of syphilis patients indicates an ongoing low-grade Treponema pallidum (T. pallidum) infection remains unanswered. To address this, we developed a machine learning model to identify T. pallidum in cell-free DNA (cfDNA) using next-generation sequencing...

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Main Authors: Meng Yin Wu, Lu Chen, Li Cheng Liu, Ming Juan Liu, Yan Feng Li, He Yi Zheng, Ling Leng, Yi Jun Zou, Wei Jun Chen, Jun Li
Format: Article
Language:English
Published: Elsevier 2024-04-01
Series:iScience
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004224006205
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author Meng Yin Wu
Lu Chen
Li Cheng Liu
Ming Juan Liu
Yan Feng Li
He Yi Zheng
Ling Leng
Yi Jun Zou
Wei Jun Chen
Jun Li
author_facet Meng Yin Wu
Lu Chen
Li Cheng Liu
Ming Juan Liu
Yan Feng Li
He Yi Zheng
Ling Leng
Yi Jun Zou
Wei Jun Chen
Jun Li
author_sort Meng Yin Wu
collection DOAJ
description Summary: The question of whether serofast status of syphilis patients indicates an ongoing low-grade Treponema pallidum (T. pallidum) infection remains unanswered. To address this, we developed a machine learning model to identify T. pallidum in cell-free DNA (cfDNA) using next-generation sequencing (NGS). Our findings showed that a TP_rate cut-off of 0.033 demonstrated superior diagnostic performance for syphilis, with a specificity of 92.3% and a sensitivity of 71.4% (AUROC = 0.92). This diagnosis model predicted that 20 out of 92 serofast patients had a persistent low-level infection. Based on these predictions, re-treatment was administered to these patients and its efficacy was evaluated. The results showed a statistically significant decrease in RPR titers in the prediction-positive group compared to the prediction-negative group after re-treatment (p < 0.05). These findings provide evidence for the existence of T. pallidum under serofast status and support the use of intensive treatment for serofast patients at higher risk in clinical practice.
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spelling doaj.art-f7fc37078b9f4b609f50b51d61a30c752024-03-17T07:58:36ZengElsevieriScience2589-00422024-04-01274109399Using circulating microbial cell-free DNA to identify persistent Treponema pallidum infection in serofast syphilis patientsMeng Yin Wu0Lu Chen1Li Cheng Liu2Ming Juan Liu3Yan Feng Li4He Yi Zheng5Ling Leng6Yi Jun Zou7Wei Jun Chen8Jun Li9Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, ChinaBeijing Macro &amp; Micro-test Bio-Tech Co., Ltd, Beijing 100083, ChinaBeijing Macro &amp; Micro-test Bio-Tech Co., Ltd, Beijing 100083, ChinaDepartment of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, ChinaDepartment of Neurology, Peking Union Medical College Hospital, Beijing 100730, ChinaDepartment of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, ChinaState Key Laboratory of Complex Severe and Rare Diseases, Translational Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, ChinaCollege of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, ChinaUniversity of Chinese Academy of Sciences, Beijing 100049, ChinaDepartment of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China; Corresponding authorSummary: The question of whether serofast status of syphilis patients indicates an ongoing low-grade Treponema pallidum (T. pallidum) infection remains unanswered. To address this, we developed a machine learning model to identify T. pallidum in cell-free DNA (cfDNA) using next-generation sequencing (NGS). Our findings showed that a TP_rate cut-off of 0.033 demonstrated superior diagnostic performance for syphilis, with a specificity of 92.3% and a sensitivity of 71.4% (AUROC = 0.92). This diagnosis model predicted that 20 out of 92 serofast patients had a persistent low-level infection. Based on these predictions, re-treatment was administered to these patients and its efficacy was evaluated. The results showed a statistically significant decrease in RPR titers in the prediction-positive group compared to the prediction-negative group after re-treatment (p < 0.05). These findings provide evidence for the existence of T. pallidum under serofast status and support the use of intensive treatment for serofast patients at higher risk in clinical practice.http://www.sciencedirect.com/science/article/pii/S2589004224006205Microbiology
spellingShingle Meng Yin Wu
Lu Chen
Li Cheng Liu
Ming Juan Liu
Yan Feng Li
He Yi Zheng
Ling Leng
Yi Jun Zou
Wei Jun Chen
Jun Li
Using circulating microbial cell-free DNA to identify persistent Treponema pallidum infection in serofast syphilis patients
iScience
Microbiology
title Using circulating microbial cell-free DNA to identify persistent Treponema pallidum infection in serofast syphilis patients
title_full Using circulating microbial cell-free DNA to identify persistent Treponema pallidum infection in serofast syphilis patients
title_fullStr Using circulating microbial cell-free DNA to identify persistent Treponema pallidum infection in serofast syphilis patients
title_full_unstemmed Using circulating microbial cell-free DNA to identify persistent Treponema pallidum infection in serofast syphilis patients
title_short Using circulating microbial cell-free DNA to identify persistent Treponema pallidum infection in serofast syphilis patients
title_sort using circulating microbial cell free dna to identify persistent treponema pallidum infection in serofast syphilis patients
topic Microbiology
url http://www.sciencedirect.com/science/article/pii/S2589004224006205
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