Practical proteomic biomarker discovery: taking a step back to leap forward

There is a pressing need for radically improved proteomic screening methods that allow for earlier diagnosis of disease, for systematic monitoring of physiological responses and for uncovering the fundamental mechanisms of drug action. Recent developments in proteomic technology offer tremendous, yet untapped, potential to yield novel biomarkers that are translatable to routine clinical use. Despite the significant conceptual promise of comparative proteomic profiling as a research platform for biomarker discovery, however, major hurdles remain for practical and clinical implementation. In particular, there is growing recognition that rigorous experimental design principles are urgently required to validate conclusively the unproven methodologies currently being touted. Debate and confusion persist about where the burden of proof lies: statistically, biologically or clinically? Moreover, there is no consensus about what constitutes a meaningful benchmark. An important question is how to achieve a scientifically rigorous, and therefore convincing, proof-of-concept that can be accepted by the field. Key analytical challenges related to these issues that must be addressed by the burgeoning biomarker community are discussed here.