Journal: medRxiv

Article Title: The Diurnal Rhythmicity of Untargeted Metabolomic Profiles in Humans

doi: 10.64898/2026.04.28.26347027

Figure Lengend Snippet: a . Forest plot of 60 blood-draw time associated serum metabolites identified in the primary combined sex models. In blue, is the cosine time of blood draw-associated metabolites and in green the sine time of blood-draw associated metabolites. Metabolites that exhibit significance in the 2df joint test (which jointly assesses both sine and cosine effects of time) are in red font. b . Pathway enrichment analysis results (false discovery rate < 0.05) for the complete set of 84 time of blood draw-associated serum metabolites discovered across combined samples, sex or age-stratified analyses, and/or primary and sensitivity models. c . Chronotype gene-metabolite connections identified by network analysis across all 84 blood draw-time associated metabolites. Pink hexagons depict serum metabolites, and green circles depict chronotype genes. d . Scatter plot of 672 serum metabolites in five clusters identified by HDBSCAN in UMAP dimensions. e . Cluster average LOWESS trends across time of blood draw. The overlaid dashed black line represents the average trajectory of metabolites with positive cosine similarity to the cluster mean and a dashed gray line for those with negative cosine similarity.

Article Snippet: Serum metabolite concentrations from baseline fasting blood samples retrieved during the day were quantified by the Metabolon, Inc.

Techniques:

Journal: medRxiv

Article Title: The Diurnal Rhythmicity of Untargeted Metabolomic Profiles in Humans

doi: 10.64898/2026.04.28.26347027

Figure Lengend Snippet: a . Fuji plot of 673 significant metabolite-trait associations (51 metabolites across 58 health traits) with adjustment of blood draw time. The outermost track displays health trait categories, and their corresponding legend color. The ‘Other’ trait category comprises of Dental, Sleep, Respiratory, Neuropsychological, and Quality of Life traits. The top five or top one most significant metabolite(s) (according to p-value significance) are annotated in the outermost track with their name, with the colored square indicating metabolite type. Metabolite types are separated each into a designated separate scatter plot track, with the tracks colored according to the legend in the bottom left. The bar plot in the upper right quadrant showcases total metabolite-trait associations identified, according to metabolite type. The following abbreviations are used: PUFA: polyunsaturated fatty acid, MUFA: monounsaturated fatty acid, SFA: saturated fatty acid, and FA: fatty acid. b . Natural log-scaled ratios comparing metabolite-trait association effect sizes from models adjusting for blood draw time, to models not adjusting for blood draw time. c . Non-zero counts of metabolite-trait associations which exhibit directional disagreement in effect size estimates between models.

Article Snippet: Serum metabolite concentrations from baseline fasting blood samples retrieved during the day were quantified by the Metabolon, Inc.

Techniques:

Journal: medRxiv

Article Title: The Diurnal Rhythmicity of Untargeted Metabolomic Profiles in Humans

doi: 10.64898/2026.04.28.26347027

Figure Lengend Snippet: a . Type 1 error under α=0.05 across three outcome scenarios (constant, in-phase with metabolite, and π/2 phase-shifted) and three causal metabolite compositions (circadian:non-circadian = 20:0, 10:10, 2:18) from the simulation analyses. b . Type 2 error under α=10 -4 across the same outcome scenarios and metabolite compositions.

Article Snippet: Serum metabolite concentrations from baseline fasting blood samples retrieved during the day were quantified by the Metabolon, Inc.

Techniques: