Mining whole sample mass spectrometry proteomics data for biomarkers: an overview

In this paper we aim to provide a concise overview of designing and conducting an MS proteomics experiment in such a way as to allow statistical analysis that may lead to the discovery of novel biomarkers. We provide a summary of the various stages that make up such an experiment, highlighting the need for experimental goals to be decided upon in advance. We discuss issues in experimental design at the sample collection stage, and good practise for standardising protocols within the proteomics laboratory. We then describe approaches to the data mining stage of the experiment, including the processing steps that transform a raw mass spectrum into a useable form. We propose a permutation-based procedure for determining the significance of reported error rates. Finally, because of its general advantages in speed and cost, we suggest that MS proteomics may be a good candidate for an early primary screening approach to disease diagnosis, identifying areas of risk and making referrals for more specific tests without necessarily making a diagnosis in its own right. Our discussion is illustrated with examples drawn from experiments on bovine blood serum conducted in the Centre for Proteomic Research (CPR) at Southampton University