A new multimodal paradigm for biomarkers longitudinal monitoring: a clinical application to women steroid profiles in urine and blood.

Autor: de Figueiredo M; School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland; Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Geneva, Switzerland., Saugy J; Center of Research and Expertise in Anti-Doping Sciences, Institute of Sport Sciences, University of Lausanne, Lausanne, Switzerland., Saugy M; Center of Research and Expertise in Anti-Doping Sciences, Institute of Sport Sciences, University of Lausanne, Lausanne, Switzerland., Faiss R; Center of Research and Expertise in Anti-Doping Sciences, Institute of Sport Sciences, University of Lausanne, Lausanne, Switzerland., Salamin O; Center of Research and Expertise in Anti-Doping Sciences, Institute of Sport Sciences, University of Lausanne, Lausanne, Switzerland; Swiss Laboratory for Doping Analyses, University Center of Legal Medicine, Lausanne and Geneva, Lausanne University, Hospital and University of Lausanne, Switzerland., Nicoli R; Swiss Laboratory for Doping Analyses, University Center of Legal Medicine, Lausanne and Geneva, Lausanne University, Hospital and University of Lausanne, Switzerland., Kuuranne T; Swiss Laboratory for Doping Analyses, University Center of Legal Medicine, Lausanne and Geneva, Lausanne University, Hospital and University of Lausanne, Switzerland., Rudaz S; School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland; Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Geneva, Switzerland., Botrè F; Center of Research and Expertise in Anti-Doping Sciences, Institute of Sport Sciences, University of Lausanne, Lausanne, Switzerland., Boccard J; School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland; Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Geneva, Switzerland. Electronic address: julien.boccard@unige.ch.
Jazyk: angličtina
Zdroj: Analytica chimica acta [Anal Chim Acta] 2023 Aug 01; Vol. 1267, pp. 341389. Date of Electronic Publication: 2023 May 17.
DOI: 10.1016/j.aca.2023.341389
Abstrakt: Background: Most current state-of-the-art strategies to generate individual adaptive reference ranges are designed to monitor one clinical parameter at a time. An innovative methodology is proposed for the simultaneous longitudinal monitoring of multiple biomarkers. The estimation of individual thresholds is performed by applying a Bayesian modeling strategy to a multivariate score integrating several biomarkers (compound concentration and/or ratio). This multimodal monitoring was applied to data from a clinical study involving 14 female volunteers with normal menstrual cycles receiving testosterone via transdermal route, as to test its ability to detect testosterone administration. The study samples consisted of urine and blood collected during 4 weeks of a control phase and 4 weeks with a daily testosterone gel application.
Results: Integrating multiple biomarkers improved the detection of testosterone gel administration with substantially higher sensitivity compared with the distinct follow-up of each biomarker, when applied to selected urine and serum steroid biomarkers, as well as the combination of both. Among the 175 known positive samples, 38% were identified by the multimodal approach using urine biomarkers, 79% using serum biomarkers and 83% by combining biomarkers from both biological matrices, whereas 10%, 67% and 64% were respectively detected using standard unimodal monitoring.
Significance and Novelty: The detection of abnormal patterns can be improved using multimodal approaches. The combination of urine and serum biomarkers reduced the overall number of false-negatives, thus evidencing promising complementarity between urine and blood sampling for doping control, as highlighted in the case of the use of transdermal testosterone preparations. The generation in a multimodal setting of adaptive and personalized reference ranges opens up new opportunities in clinical and anti-doping profiling. The integration of multiple parameters in a longitudinal monitoring is expected to provide a more complete evaluation of individual profiles generating actionable intelligence to further guide sample collection, analysis protocols and decision-making in clinics and anti-doping.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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