Proteomics

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


ABSTRACT: 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.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Serum

SUBMITTER: Lee Gethings  

LAB HEAD: Lee Gethings

PROVIDER: PXD055555 | Pride | 2025-05-07

REPOSITORIES: Pride

Dataset's files

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080923_001.mzML Mzml
080923_001.raw.zip Raw
080923_002.mzML Mzml
080923_002.raw.zip Raw
080923_003.mzML Mzml
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Publications

Challenges and opportunities for statistical power and biomarker identification arising from rhythmic variation in proteomics.

Spick Matt M   Isherwood Cheryl M CM   Gethings Lee A LA   Hughes Christopher J CJ   Daly Matthew E ME   Hassanin Hana H   van der Veen Daan R DR   Skene Debra J DJ   Johnston Jonathan D JD  

Npj biological timing and sleep 20250125 1


Time-of-day variation in the molecular profile of biofluids and tissues is a well-described phenomenon, but-especially for proteomics-is rarely considered in terms of the challenges this presents to reproducible biomarker identification. We provide a case study analysis of human circadian and ultradian rhythmicity in proteins, including in the complement and coagulation cascades and apolipoproteins, with PLG, CFAH, ZA2G and ITIH2 demonstrated as rhythmic for the first time. We also show that rhy  ...[more]

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