Rhythmic variation in proteomics: challenges and opportunities for statistical power and biomarker identification

Time-of-day variation in the molecular profile of biofluids and ssues is a well-described phenomenon, but – especially for proteomics – is rarely considered in terms of the challenges this presents to reproducible biomarker identification. In this work we demonstrate these confounding issues using a small-scale proteomics analysis of male participants in a constant routine protocol following an 8-day laboratory study, in which sleep-wake, light-dark and meal timings were controlled. We provide a case study analysis of circadian and ultradian rhythmicity in proteins in the complement and coagulation cascades, as well as apolipoproteins, and demonstrate that rhythmicity increases the risk of Type II errors due to the reduction in statistical power from increased variance.