Fig. 6.
Time-awake–dependent variations in the transcriptome. (A) Genes with a prevalent time-awake–dependent variation during the constant routine/total sleep deprivation following the control condition (124 probes that target 122 genes, FDR <5%). Medians of the melatonin-aligned probe values across all participants in the control condition are clustered based on a circular SOM. Cluster means are plotted as time-series and the number of genes per cluster is indicated in parenthesis (genes belonging to multiple clusters are counted in each cluster independently). Sampling times and melatonin profile shown correspond to the average values across all participants in the control condition. (B–D) Data are based on genes with a prevalent time-awake variation during the constant routine/total sleep deprivation after sleep restriction and not significantly prevalent after control (363 probes that target 361 genes with cumulative upward trend, and 470 probes that target 444 genes with cumulative downward trend; see Fig. 3 B and C). (B) Heatmap rows correspond to the median of the melatonin-aligned probe values across all participants per sleep condition. Rows are clustered based on a circular SOM of the sleep-restriction profiles. Color codes to the left of the heat map identify the clusters. Relative clock time and melatonin profile are the average values across all participants per condition. Genes related to circadian rhythmicity and sleep (according to Gene Ontology) are indicated in the heatmap (gene colors indicate cluster location). (C) Smoothing spline (64) of the average of melatonin-aligned median profiles (shown in B) of probes with an increasing trend and of probes with a decreasing trend. (D) Density plot of cumulative trend angle differences between sleep restriction and control. A total of 1,838 paired trend angles (363 probes significant in an average of 5.06 participants) were used for the comparison of upward trends, and a total of 2,454 paired trend angles (470 probes significant in an average of 5.22 participants) were used for the comparison of downward trends. For upward trend (orange), the estimated mean of the differences is 20.1085° [95% CI (19.3552, 20.8618), indicated by orange broken lines; t test P < 2.2 × 10−16]. For downward trend (blue), the estimated mean of the differences is −21.1062° [95% CI (−21.7344, −20.4781), indicated by blue broken lines; t test P < 2.2 × 10−16].