Circulating Salivary miRNA hsa-miR-221 as Clinically Validated Diagnostic Marker for Hand, Foot, and Mouth Disease in Pediatric Patients
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
Affiliations
Nyo Min
Laboratory 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
Previtha Dawn Sakthi Vale
Laboratory 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
Anng Anng Wong
Infectious Disease Service, Department of Pediatric Medicine, KK Women's and Children's Hospital, 100 Bukit Timah Road, 229899, Singapore
Natalie Woon Hui Tan
Infectious Disease Service, Department of Pediatric Medicine, KK Women's and Children's Hospital, 100 Bukit Timah Road, 229899, Singapore
Chia Yin Chong
Infectious Disease Service, Department of Pediatric Medicine, KK Women's and Children's Hospital, 100 Bukit Timah Road, 229899, Singapore
Chih-Jung Chen
Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Memorial and Children's Hospital, Linkuo 33305, Taiwan
Robert Y.L. Wang
Division 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, Taiwan
Justin Jang Hann Chu
Laboratory 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 learning
