Circulating Salivary miRNA hsa-miR-221 as Clinically Validated Diagnostic Marker for Hand, Foot, and Mouth Disease in Pediatric Patients

Enhancements in the diagnostic capabilities using host biomarkers are currently much needed where sensitivity and specificity issues plague the diagnosis of Hand, Foot and Mouth Disease (HFMD) in pediatrics clinical samples. We investigated miRNome profiles of HFMD saliva samples against healthy chi...

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Main Authors: Nyo Min, Previtha Dawn Sakthi Vale, Anng Anng Wong, Natalie Woon Hui Tan, Chia Yin Chong, Chih-Jung Chen, Robert Y.L. Wang, Justin Jang Hann Chu
Format: Article
Language:English
Published: Elsevier 2018-05-01
Series:EBioMedicine
Online Access:http://www.sciencedirect.com/science/article/pii/S2352396418301610
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author Nyo Min
Previtha Dawn Sakthi Vale
Anng Anng Wong
Natalie Woon Hui Tan
Chia Yin Chong
Chih-Jung Chen
Robert Y.L. Wang
Justin Jang Hann Chu
author_facet Nyo Min
Previtha Dawn Sakthi Vale
Anng Anng Wong
Natalie Woon Hui Tan
Chia Yin Chong
Chih-Jung Chen
Robert Y.L. Wang
Justin Jang Hann Chu
author_sort Nyo Min
collection DOAJ
description Enhancements in the diagnostic capabilities using host biomarkers are currently much needed where sensitivity and specificity issues plague the diagnosis of Hand, Foot and Mouth Disease (HFMD) in pediatrics clinical samples. We investigated miRNome profiles of HFMD saliva samples against healthy children and developed miRNA-based diagnosis models. Our 6-miRNA scoring model predicted HFMD with an overall accuracy of 85.11% in the training set and 92.86% in the blinded test set of Singapore cohort. Blinded evaluation of the model in Taiwan HFMD cases resulted in 77.08% accuracy with the 6-miRNA model and 68.75% with the 4-miRNA model. The strongest predictor of HFMD in all of the panels, hsa-miR-221 was found to be consistently and significantly downregulated in all of our HFMD cohorts. This is the first study to prove that HFMD infection could be diagnosed by circulating miRNAs in patient's saliva. Moreover, this study also serves as a stepping stone towards the future development of other infectious disease diagnosis workflows using novel biomarkers. Keywords: miRNA, Biomarker, Saliva, HFMD, Machine learning
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spelling doaj.art-b57c732d255542779ebb5a180b690da22022-12-21T18:53:27ZengElsevierEBioMedicine2352-39642018-05-0131299306Circulating Salivary miRNA hsa-miR-221 as Clinically Validated Diagnostic Marker for Hand, Foot, and Mouth Disease in Pediatric PatientsNyo Min0Previtha Dawn Sakthi Vale1Anng Anng Wong2Natalie Woon Hui Tan3Chia Yin Chong4Chih-Jung Chen5Robert Y.L. Wang6Justin Jang Hann Chu7Laboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University Health System, 5 Science Drive 2, National University of Singapore, 117597, SingaporeLaboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University Health System, 5 Science Drive 2, National University of Singapore, 117597, SingaporeInfectious Disease Service, Department of Pediatric Medicine, KK Women's and Children's Hospital, 100 Bukit Timah Road, 229899, SingaporeInfectious Disease Service, Department of Pediatric Medicine, KK Women's and Children's Hospital, 100 Bukit Timah Road, 229899, SingaporeInfectious Disease Service, Department of Pediatric Medicine, KK Women's and Children's Hospital, 100 Bukit Timah Road, 229899, SingaporeDivision of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Memorial and Children's Hospital, Linkuo 33305, TaiwanDivision of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Memorial and Children's Hospital, Linkuo 33305, Taiwan; Department of Biomedical Sciences, College of Medicine, Chang Gung University, TaoYuan 33302, TaiwanLaboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University Health System, 5 Science Drive 2, National University of Singapore, 117597, Singapore; Collaborative and Translational Unit for HFMD, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore; Corresponding author.Enhancements in the diagnostic capabilities using host biomarkers are currently much needed where sensitivity and specificity issues plague the diagnosis of Hand, Foot and Mouth Disease (HFMD) in pediatrics clinical samples. We investigated miRNome profiles of HFMD saliva samples against healthy children and developed miRNA-based diagnosis models. Our 6-miRNA scoring model predicted HFMD with an overall accuracy of 85.11% in the training set and 92.86% in the blinded test set of Singapore cohort. Blinded evaluation of the model in Taiwan HFMD cases resulted in 77.08% accuracy with the 6-miRNA model and 68.75% with the 4-miRNA model. The strongest predictor of HFMD in all of the panels, hsa-miR-221 was found to be consistently and significantly downregulated in all of our HFMD cohorts. This is the first study to prove that HFMD infection could be diagnosed by circulating miRNAs in patient's saliva. Moreover, this study also serves as a stepping stone towards the future development of other infectious disease diagnosis workflows using novel biomarkers. Keywords: miRNA, Biomarker, Saliva, HFMD, Machine learninghttp://www.sciencedirect.com/science/article/pii/S2352396418301610
spellingShingle Nyo Min
Previtha Dawn Sakthi Vale
Anng Anng Wong
Natalie Woon Hui Tan
Chia Yin Chong
Chih-Jung Chen
Robert Y.L. Wang
Justin Jang Hann Chu
Circulating Salivary miRNA hsa-miR-221 as Clinically Validated Diagnostic Marker for Hand, Foot, and Mouth Disease in Pediatric Patients
EBioMedicine
title Circulating Salivary miRNA hsa-miR-221 as Clinically Validated Diagnostic Marker for Hand, Foot, and Mouth Disease in Pediatric Patients
title_full Circulating Salivary miRNA hsa-miR-221 as Clinically Validated Diagnostic Marker for Hand, Foot, and Mouth Disease in Pediatric Patients
title_fullStr Circulating Salivary miRNA hsa-miR-221 as Clinically Validated Diagnostic Marker for Hand, Foot, and Mouth Disease in Pediatric Patients
title_full_unstemmed Circulating Salivary miRNA hsa-miR-221 as Clinically Validated Diagnostic Marker for Hand, Foot, and Mouth Disease in Pediatric Patients
title_short Circulating Salivary miRNA hsa-miR-221 as Clinically Validated Diagnostic Marker for Hand, Foot, and Mouth Disease in Pediatric Patients
title_sort circulating salivary mirna hsa mir 221 as clinically validated diagnostic marker for hand foot and mouth disease in pediatric patients
url http://www.sciencedirect.com/science/article/pii/S2352396418301610
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