Aptamer based proteomic pilot study reveals a urine signature indicative of pediatric urinary tract infections.

Liang Dong,David S Hains,Joshua Watson,Andrew L Schwaderer,Jeffrey M Caterino,Sha Cao,Samuel Arregui,Vijay Saxena,John Ketz,Abduselam K Awol,Daniel M Cohen,Mehreen Arshad

doi:10.1371/journal.pone.0235328

Abstract

Current urinary tract infection (UTI) diagnostic strategies that rely on leukocyte esterase have limited accuracy. We performed an aptamer-based proteomics pilot study to identify urine protein levels that could differentiate a culture proven UTI from culture negative samples, regardless of pyuria status. We analyzed urine from 16 children with UTIs, 8 children with culture negative pyuria and 8 children with negative urine culture and no pyuria. The urine levels of 1,310 proteins were quantified using the Somascan™ platform and normalized to urine creatinine. Machine learning with support vector machine (SVM)-based feature selection was performed to determine the combination of urine biomarkers that optimized diagnostic accuracy. Eight candidate urine protein biomarkers met filtering criteria. B-cell lymphoma protein, C-X-C motif chemokine 6, C-X-C motif chemokine 13, cathepsin S, heat shock 70kDA protein 1A, mitogen activated protein kinase, protein E7 HPV18 and transgelin. AUCs ranged from 0.91 to 0.95. The best prediction was achieved by the SVMs with radial basis function kernel. Biomarkers panel can be identified by the emerging technologies of aptamer-based proteomics and machine learning that offer the potential to increase UTI diagnostic accuracy, thereby limiting unneeded antibiotics.

Highlights

Urinary tract infections (UTIs) are frequently encountered
Machine learning with support vector machine (SVM)-based feature selection was performed to determine the combination of urine biomarkers that optimized diagnostic accuracy
Biomarkers panel can be identified by the emerging technologies of aptamer-based proteomics and machine learning that offer the potential to increase UTI diagnostic accuracy, thereby limiting unneeded antibiotics

Summary

Introduction

UTIs account for 7 million office visits and 400,000 hospitalizations annually in the United States [1, 2]. The aforementioned hospitalizations for UTIs increased 52% between 1998 and 2011 and resulted in an estimated 2.8 billion dollars of cost. The diagnosis of UTIs is typically made at the point of care by symptoms and the identification of nitrites and /or leukocyte esterase (LE) on urinalysis (UA) and/or urine dipstick [5]. Urine culture results with 50,000 colony forming units (cfu)/ml of a uropathogen is used to confirm a clinical UTI [5]. Non UTI, infectious and/or inflammatory conditions such chlamydia, appendicitis and interstitial nephritis can result in positive urine leukocyte esterase and negative urine cultures [7]

Results

Discussion

Conclusion