MSACL 2019 EU Abstract

Biomarker Discovery and Translational Research Leading to Clinical Utility: Experimental Approaches and Pitfalls

Christiane Auray-Blais, Michel Boutin
Université de Sherbrooke, Sherbrooke, Quebec, Canada

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Christiane/Michel Auray-Blais/Boutin (Presenter) Université de Sherbrooke

Presenter Bio: Christiane Auray-Blais, LL.M., Ph.D. is the Director of the Neonatal Urine Screening Program for hereditary metabolic disorders in Sherbrooke, QC. She is the author of more than 275 publications, book chapters, abstracts and articles. She is a full professor in the Medical Genetics Division in the Department of Pediatrics at the Université de Sherbrooke. She is the principal investigator/co-investigator in numerous research grants. She has received awards for her involvement and expertise in preventive genetic medicine.

Michel Boutin, Ph.D., worked for 2 years as a scientific assistant for a proteomic platform (Université Laval, QC). Since 2011, he is the technical director of the Water-CHUS Expertise Centre in Clinical Mass Spectrometry (Faculty of Medicine and Health Sciences, Clinical Research Centre-CHUS, Sherbrooke, QC) and adjunct teacher at Université de Sherbrooke for 2 years.

Relevant Financial Disclosures (within past 24 months) Honorarium/Expenses C. Auray-Blais and M. Boutin received expense support from Waters Discussing Products? NO, presenter will NOT present educational content related to products/services of the ineligible company(ies) listed above. Conflict mitigation NOT REQUIRED.

This session will focus on three aspects of clinical analyses: 1) the discovery of biomarkers using semi- and untargeted metabolomic approaches; 2) the “de novo” structural elucidation of biomarkers; and 3) the quantitative analysis of biomarkers in the clinical field. The focus on biomarker discovery will be on the choice, collection and preparation of samples for optimal results and to prevent the risk to create artificial biases between the patient and control groups. Different aspects concerning the UPLC/MS analysis of samples will be addressed to increase the quality of the dataset and to obtain the necessary information to optimize the alignment (data mining) of the results. Other tools, such as various mathematical transformations applied to the marker peak areas, will be presented to improve biomarker discovery based on their abundance. Multivariate analyses, mainly the supervised orthogonal partial least-square discriminant analysis (OPLS-DA) statistical method, will show how to target biomarker candidates. In the second part of the seminar, tips on the structural elucidation of biomarkers by tandem mass spectrometry will be presented. Often, novel biomarkers are not listed in tandem mass spectrometry data banks. Therefore, tools will be presented to perform “de novo” structural elucidation of molecules. The issue related to the presence of structural isomers interfering with the interpretation of a biomarker fragmentation spectrum will be presented. The last part of the seminar will be dedicated to the development and validation of Multiple Reaction Monitoring (MRM) methods for the quantitative analysis of biomarkers. Two examples of UPLC methods optimization allowing the separation of the biomarker from structural isomer interferences will be presented as well as how to reduce matrix effects. During this Practical Training Track presentation, biomarker results for Parkinson’s disease and various genetic diseases such as Fabry and Gaucher diseases will be used as clinical applications.