Diurnal rhythm of the human plasma proteome

. 2025 Aug 22;22:29. doi: 10.1186/s12014-025-09551-7

Research in context
Evidence before this study Blood sampling is fundamental to diagnosis and treatment in hospital settings. However, research on circadian and diurnal rhythms in the plasma proteome, and their implications for diagnostic accuracy, remains limited. We searched Google Scholar up to February 26, 2025, using the terms “Plasma Proteins and Circadian Rhythm”, “Plasma Proteins and Diurnal Variations”, “Circadian Rhythm and Plasma Proteome” and “Mass Spectrometry, Plasma Proteomics and Circadian Rhythm”. We identified fewer than five relevant studies, most of which relied on SomaScan aptamer-based assays that provide only partial protein coverage and may introduce bias in specificity and quantitation. Consequently, unbiased mass-spectrometry analyses of circadian and diurnal rhythm protein variation in healthy individuals are lacking. This gap hinders our understanding of how time-of-day protein fluctuations affect patient testing, protein research and ultimately diagnostic accuracy Added value of this study	Using a high-throughput, unbiased mass spectrometry approach with multiple time point sampling in 24 healthy individuals, we found that 26% of plasma proteins exhibited significant diurnal rhythms. Our study offers a comprehensive overview of how the plasma proteome varies by time-of-day, providing critical insights that can guide future research and help refine diagnostic protocols Implications of all the available evidence These findings suggest that time-of-day fluctuations in plasma proteins may be relevant to the interpretation of clinical blood tests. However, additional research in larger and more diverse cohorts is needed to determine whether standardized sampling times or time-sensitive reference ranges would improve diagnostic accuracy and patient outcomes. Moreover, our results imply that previous proteomic investigations may have been influenced by the lack of circadian and diurnal consideration, emphasizing the potential value of carefully timed sampling and diurnal considerations in future diagnostics, treatment and research

Research in context

Evidence before this study Blood sampling is fundamental to diagnosis and treatment in hospital settings. However, research on circadian and diurnal rhythms in the plasma proteome, and their implications for diagnostic accuracy, remains limited. We searched Google Scholar up to February 26, 2025, using the terms “Plasma Proteins and Circadian Rhythm”, “Plasma Proteins and Diurnal Variations”, “Circadian Rhythm and Plasma Proteome” and “Mass Spectrometry, Plasma Proteomics and Circadian Rhythm”. We identified fewer than five relevant studies, most of which relied on SomaScan aptamer-based assays that provide only partial protein coverage and may introduce bias in specificity and quantitation. Consequently, unbiased mass-spectrometry analyses of circadian and diurnal rhythm protein variation in healthy individuals are lacking. This gap hinders our understanding of how time-of-day protein fluctuations affect patient testing, protein research and ultimately diagnostic accuracy

Added value of this study

Using a high-throughput, unbiased mass spectrometry approach with multiple time point sampling in 24 healthy individuals, we found that 26% of plasma proteins exhibited significant diurnal rhythms. Our study offers a comprehensive overview of how the plasma proteome varies by time-of-day, providing critical insights that can guide future research and help refine diagnostic protocols

Implications of all the available evidence

These findings suggest that time-of-day fluctuations in plasma proteins may be relevant to the interpretation of clinical blood tests. However, additional research in larger and more diverse cohorts is needed to determine whether standardized sampling times or time-sensitive reference ranges would improve diagnostic accuracy and patient outcomes. Moreover, our results imply that previous proteomic investigations may have been influenced by the lack of circadian and diurnal consideration, emphasizing the potential value of carefully timed sampling and diurnal considerations in future diagnostics, treatment and research