The use of mass spectrometry for analysing metabolite biomarkers in epidemiology: methodological and statistical considerations for application to large numbers of biological samples

Data quality is critical for epidemiology, and as scientific understanding expands, the range of data available for epidemiological studies and the types of tools used for measurement have also expanded. It is essential for the epidemiologist to have a grasp of the issues involved with different measurement tools. One tool that is increasingly being used for measuring biomarkers in epidemiological cohorts is mass spectrometry (MS), because of the high specificity and sensitivity of MS-based methods and the expanding range of biomarkers that can be measured. Further, the ability of MS to quantify many biomarkers simultaneously is advantageously compared to single biomarker methods. However, as with all methods used to measure biomarkers, there are a number of pitfalls to consider which may have an impact on results when used in epidemiology. In this review we discuss the use of MS for biomarker analyses, focusing on metabolites and their application and potential issues related to large-scale epidemiology studies, the use of MS "omics" approaches for biomarker discovery and how MS-based results can be used for increasing biological knowledge gained from epidemiological studies. Better understanding of the possibilities and possible problems related to MS-based measurements will help the epidemiologist in their discussions with analytical chemists and lead to the use of the most appropriate statistical tools for these data.