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Translational biomarker discovery in clinical metabolomics: an introductory tutorial

By:
Contributors: David Broadhurst, PhD

Metabolomics. 2013 Apr;9(2):280-299. Epub 2012 Dec 4.

Xia J1, Broadhurst DI, Wilson M, Wishart DS.

 

Abstract

Metabolomics is increasingly being applied towards the identification of biomarkers for disease diagnosis, prognosis and risk prediction. Unfortunately among the many published metabolomic studies focusing on biomarker discovery, there is very little consistency and relatively little rigor in how researchers select, assess or report their candidate biomarkers. In particular, few studies report any measure of sensitivity, specificity, or provide receiver operator characteristic (ROC) curves with associated confidence intervals. Even fewer studies explicitly describe or release the biomarker model used to generate their ROC curves. This is surprising given that for biomarker studies in most other biomedical fields, ROC curve analysis is generally considered the standard method for performance assessment. Because the ultimate goal of biomarker discovery is the translation of those biomarkers to clinical practice, it is clear that the metabolomics community needs to start “speaking the same language” in terms of biomarker analysis and reporting-especially if it wants to see metabolite markers being routinely used in the clinic. In this tutorial, we will first introduce the concept of ROC curves and describe their use in single biomarker analysis for clinical chemistry. This includes the construction of ROC curves, understanding the meaning of area under ROC curves (AUC) and partial AUC, as well as the calculation of confidence intervals. The second part of the tutorial focuses on biomarker analyses within the context of metabolomics. This section describes different statistical and machine learning strategies that can be used to create multimetabolite biomarker models and explains how these models can be assessed using ROC curves. In the third part of the tutorial we discuss common issues and potential pitfalls associated with different analysis methods and provide readers with a list of nine recommendations for biomarker analysis and reporting. To help readers test, visualize and explore the concepts presented in this tutorial, we also introduce a web-based tool called ROCCET (ROC Curve Explorer & Tester, http://www.roccet.ca). ROCCET was originally developed as a teaching aid but it can also serve as a training and testing resource to assist metabolomics researchers build biomarker models and conduct a range of common ROC curve analyses for biomarker studies.

PubMed

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Congratulations to first place winner Doug Brown!

Congratulations to PhD grad student Doug Brown for his First Place win at the 2018 University of Alberta Student Falling Walls Lab Competition! Doug’s First Place award also gains him an entry and an all-expenses-paid trip to the highly competitive and prestigious Falling Walls Lab Conference in Berlin, November 8-9, 2018!

Fifteen student presenters pitched their innovative and globally-important research ideas in a short 3 minute presentation to a panel of science and tech-business savvy judges and a large cheering audience on September 19, 2018, at the University of Alberta in a high-stakes “TEDTalk” meets “Dragon’s Den” style. The competition was very strong but Doug gave an inspired speech on breaking down the walls of metastatic cancers using new lipid nanoparticle technology that he is helping to develop during his graduate studies in Dr. John Lewis’ laboratory.

The Sept 19th UofA Falling Walls Lab competition will be featured on Global News on the evening of Sept. 20th, around 6:15 pm. Check it out!

Doug will be taking his pitch to the Falling Walls Lab competition in Berlin, Germany this November where he will compete with many other inspirational students at this international event.

This is doubly exciting for the Lewis lab because John Lewis recently won the UofA Falling Walls Venture competition that was held on Aug 29, 2018 and he will be competing in the Berlin Falling Walls Venture!

Good luck to both Doug and John at the Falling Walls Finale in Berlin!

- Perrin Beatty