1. Combination of the fetal urinary metabolome and peptidome for the prediction of postnatal renal outcome in fetuses with PUV.
- Author
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Buffin-Meyer B, Klein J, Breuil B, Muller F, Moulos P, Groussolles M, Bouali O, Bascands JL, Decramer S, and Schanstra JP
- Subjects
- Biomarkers urine, Female, Fetal Diseases diagnosis, Fetal Diseases urine, Fetus metabolism, Humans, Infant, Newborn, Infant, Newborn, Diseases urine, Kidney Failure, Chronic urine, Male, Peptide Fragments analysis, Predictive Value of Tests, Pregnancy, Pregnancy Outcome, Prognosis, Proteome analysis, Proteome metabolism, Retrospective Studies, Urethral Stricture congenital, Urethral Stricture diagnosis, Urethral Stricture urine, Urinalysis methods, Infant, Newborn, Diseases diagnosis, Kidney Failure, Chronic congenital, Kidney Failure, Chronic diagnosis, Metabolome physiology, Peptide Fragments urine, Prenatal Diagnosis methods
- Abstract
Most of biomarker panels, extracted from single omics traits, still need improvement since they display a gray zone where prediction is uncertain. Here we verified whether a combination of omics traits, fetal urinary metabolites and peptides analyzed in the same sample, improved prediction of postnatal renal function in fetuses with posterior urethral valves (PUV) compared to individual omics traits. Using CE-MS, we explored the urinary metabolome of 13 PUV fetuses with end stage renal disease (ESRD) and 12 PUV fetuses without postnatal ESRD at 2 years postnatally. This allowed the selection of 24 differentially abundant metabolite features which were modelled into predictive classifiers, alone or in combination with 12 peptides previously identified as predictive of ESRD. Validation in 35 new fetuses showed that the combination of peptides and metabolites significantly outperformed the 24 metabolite features with increased AUC (0.987 vs 0.905), net reclassification improvement (36%) and better sensitivity accuracy (86% vs 60%). In addition, the two trait combination tended to improve, but without reaching statistical significance, the already high performances of the 12 peptide biomarkers (AUC 0.967, accuracy 80%). In conclusion, this study demonstrates the potential of cumulating different omics traits in biomarker research where single omics traits fall short., Significance: Although increasingly proposed in disease-diagnosis and -prognosis because of their improved efficacy over single markers, panels of body fluid biomarkers based on single omics analysis still fail to display perfect accuracy, probably due to biological variability. Here, we hypothesized that combination of different omics traits allowed to better capture this biological variability. As proof of concept, we studied the added value of fetal urine metabolites and peptides using CE-MS, starting from the same urine sample, to predict postnatal renal outcome in fetuses with posterior urethral valves. We observed that the prognostic power of combined metabolite and peptide markers was clearly higher than that of metabolites alone and slightly, but non-significantly, improved compared to the peptides alone. To our knowledge, this report is the first to demonstrate that combining multiomics traits extracted from (fetal) urine samples displays clear promise for kidney disease stratification., (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Published
- 2018
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