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. 2023 Apr 24;120(18):e2212685120. doi: 10.1073/pnas.2212685120

Table 1.

Comparison with DLMO estimation studies in humans using blood molecular markers

Refence Condition Sex N Age (y) Method #F Measures T R2 MdAE (h)
Laing et al. (15)* CR, FD f;m 24;25 27.1 (3.7) TimeTable 73 Blood mRNA 1 0.49 3.13
2 0.69 2.45
3 0.82 1.87
ZeitZeiger 107 1 0.47 3.18
2 0.69 2.43
3 0.78 2.07
PLSR 100 1 0.74 2.22
2 0.83 1.80
3 0.88 1.52
dTimeTable 73 2 0.78 1.67
dPLSR 100 2 0.90 1.13
Wittenbrink et al. (17)§ (1) CR m 12 25.3 (2.6) ZeitZeiger 32 RNAseq 1 - 1.6
30 2 - 1.4
(2) 30 NanoString 1 - 0.8
29 2 - 0.7
(3) NL f, m 17, 11 26.9 (5.7) 2 1 - 0.54
2 2 - 0.75
Kervezee et al. (23) CR f, m 1, 10 24.1 (18–30) PLSR 200 Blood mRNA 1 0.83 2.1
Braun et al. (18)* (1) CR f, m 12, 14 27.5 (4.3) TimeSignature 41 Blood mRNA 2 - 1.2
(2) FD f, m 11, 11 26.3 (3.4) - 1.85
(3) CR - 11 - - 1.20
mean 1.42
(1) CR f, m 12, 14 27.5 (4.3) dPLSR 100 Blood mRNA 2 - 0.98
(2) FD f, m 11, 11 26.3 (3.4) - 2.17
(3) CR - 11 - - 1.10
mean 1.42
Cogswell et al. (19) (1) LD baseline f, m 8, 8 22.4 (4.8) PLSR (DLMO) 100 Untargeted blood metabolites 1 0.61 2.2
(2) LD 5h sleep 0.6 2.1
(3) LD 9h sleep 0.56 2.6
mean 0.6 2.2
(1) LD baseline PLSR (DLMOff) 300 1 0.91 1.1
(2) LD 5h sleep 0.44 3.7
(3) LD 9h sleep 0.5 3.3
mean 0.62 1.8
Woelders et al., 2023 (this study) LD f 12 24.8 (4.4) PLSR 131 Targeted blood metabolites 1 - 1.02 (1.54)
2 - 0.45 (1.16)
3 - 0.30 (1.02)
m 12 22.7 (4.5) PLSR 131 Targeted blood metabolites 1 - 0.96 (1.48)
2 - 0.60 (1.15)
3 - 0.26 (1.01)

Variables: condition (FD, forced desynchrony; CR, constant routine; LD, light-dark cycle), sex (f= female, m= male), N=sample size for constructing the model (females, males), age [average and (SD)], method (statistical modeling approach), #F (number of features: 24-h gene expression or metabolite profiles required to train the model), measures (type of measurements used), T (number of sample timepoints used to construct a daily profile for each feature), R2 (model fit), MdAE (median absolute error) indicating the median central measure of the individual differences in hours between the estimated and true DLMO. Where necessary, MdAE was estimated from SD given in the original reference by 100,000 Monte Carlo simulation runs. For the current study (bottom rows), our random sample selection (in brackets) compares favorably with the error estimates of the other studies. Improving DLMO estimation by optimized timing of samples according to sex improved the performance of the algorithm considerably (bold MdAE values).

*The combined datasets of Archer et al. (24) and Möller-Levet et al. (25) were used in Laing et al. (15), which respectively correspond to datasets (1) and (2) that were re-analysed by Braun et al. (18).

Collection under dim light CR with or without prior sleep restriction.

Collection under dim light and darkness during FD with sleep in or out of phase with melatonin.

§Measured in isolated monocytes.

Participants were exposed to either both FD conditions, or both CR conditions.