Supplementary Materials for “Estimating Periodicity of Oscillatory Time Series Through Resampling Techniques” by Maria J. Costa, Bärbel F. Finkenstädt, Peter D. Gould, Julia Foreman, Karen Halliday, Anthony Hall, and David A. Rand Additional plots from simulation studies The definition of outlier used in this paper is motivated by biological rather than distributional arguments. Hence, the boxplots in this web appendix are constructed in a slightly different way. The three central lines composing the box correspond to the usual 25th, 50th and 75th percentiles of the simulated distribution of log10 (SqE) for both the SR method and the FFTNLLS routine excluding all the so-called outliers. However, the whiskers now correspond to the observed minimum and maximum of log10 (SqE) associated with period estimates within the circadian range. 1 NC = 4, n = 30 8 4 4 log (SqE) 0 10 10 log (SqE) NC = 2, n = 30 8 −4 −8 0 −4 SR −8 otl−FFT−NLLS SR NC = 4, n = 60 8 8 4 4 log (SqE) 0 10 10 log (SqE) NC = 2, n = 60 −4 −8 0 −4 SR −8 otl−FFT−NLLS SR otl−FFT−NLLS NC = 4, n = 240 8 4 4 log (SqE) 0 10 10 log (SqE) NC = 2, n = 240 8 −4 −8 otl−FFT−NLLS 0 −4 SR −8 otl−FFT−NLLS SR otl−FFT−NLLS Supplementary Figure 1. Boxplots of log10 (SqE) for period estimates obtained from synthetic mRNA dynamics for both the SR and the FFT-NLLS methods. In all the plots the dotted line corresponds to the 50th percentile of the distribution of log10 (SqE) for the SR method. The crosses represent values of log10 (SqE) associated with outliers. 2 mRNA level Mild Asymmetry Severe Asymmetry 600 600 400 400 400 200 200 200 0 Transcription Moderate Asymmetry 600 0 50 100 0 0 50 100 0 300 300 300 200 200 200 100 100 100 0 0 50 100 Time (hours) 0 0 50 100 Time (hours) 0 0 0 50 100 50 100 Time (hours) Supplementary Figure 2. Dynamics of synthetic mRNA (top panels) and corresponding transcription functions (bottom panels) for the different asymmetry levels. From left to right, mild asymmetry level, moderate asymmetry level, and severe asymmetry level. Markers represent synthetic hourly mRNA observations. 3 Moderate Asymmetry 4 0 0 10 log (SqE) 4 −4 −4 −8 −8 SR otl−FFT−NLLS SR otl−FFT−NLLS Severe Asymmetry 4 log10(SqE) log10(SqE) Mild Asymmetry 0 −4 −8 SR otl−FFT−NLLS Supplementary Figure 3. Boxplots of log10 (SqE) for period estimates obtained from synthetic mRNA dynamics satisfying all three levels of asymmetry using both the SR and FFT-NLLS methods. In all the plots the dotted line corresponds to the 50th percentile of the distribution of log10 (SqE) for the SR method. Crosses represent values of log10 (SqE) associated with outliers. 4 mRNA level Mild Shoulder Severe Shoulder 400 400 300 300 300 200 200 200 100 100 100 0 τ(t) Moderate Shoulder 400 0 50 100 0 0 50 100 0 0.8 0.8 0.8 0.6 0.6 0.6 0.4 0.4 0.4 0.2 0.2 0.2 0 0 50 100 0 Time (hours) 0 50 Time (hours) 100 0 0 0 50 100 50 100 Time (hours) Supplementary Figure 4. Dynamics of synthetic mRNA (top panels) and corresponding transcription rates τ(t) (bottom panels) for the different shoulder models. From left to right, mild shoulder level, moderate shoulder level, and severe shoulder level. Markers represent synthetic hourly mRNA observations. 5 Moderate Shoulder 6 6 4 4 10 log (SqE) 8 2 2 0 0 −2 −2 SR otl−FFT−NLLS SR otl−FFT−NLLS Severe Shoulder 8 6 log10(SqE) log10(SqE) Mild Shoulder 8 4 2 0 −2 SR otl−FFT−NLLS Supplementary Figure 5. Boxplots of log10 (SqE) for period estimates obtained from synthetic mRNA dynamics satisfying all three levels of shoulder pattern using both the SR and FFT-NLLS methods. In all the plots the dotted line corresponds to the 50th percentile of the distribution of log10 (SqE) for the SR method. Crosses represent values of log10 (SqE) associated with outliers. 6 ni = 8, νi = 0.05, σr = 0.1 ni = 16, νi = 0.05, σr = 0.1 i i T0 0.04 T0 0.04 T1 T1 T2 T2 K.05 0.02 Size discrepancy Size discrepancy K.05 0 −0.02 −0.04 0 0.02 0 −0.02 −0.04 0.2 0.4 0.6 Nominal size 0.8 1 0 0.2 ni = 8, νi = 0.08, σr = 0.2 0.4 0.6 Nominal size 0.8 ni = 16, νi = 0.08, σr = 0.2 i i T0 0.04 T0 0.04 T1 T1 T2 T2 K.05 0.02 Size discrepancy Size discrepancy K.05 0 −0.02 −0.04 0 1 0.02 0 −0.02 −0.04 0.2 0.4 0.6 Nominal size 0.8 1 0 0.2 0.4 0.6 Nominal size 0.8 Supplementary Figure 6. P-value discrepancy plots for hypotheses tests T 0 , T 1 and T 2 for different parameter combinations. In all cases, ri = 0.5, i = 1, 2. Horizontal lines represent 5% critical value of the Kolmogorov-Smirnov test, K.05 . 7 1 δ = 0.5, n1 = n2 = 32 δ = 1.5, n1 = n2 = 32 1 1 0.8 0.8 T0 T0 T1 T1 T2 Power 0.6 0.6 0.4 0.4 0.2 0.2 0 0 0.05 0.1 Size 0.15 0 0.2 0 0.05 0.1 Size 0.15 δ = 1.5, n1 = 16, n2 = 32 1 0.8 T0 T1 T2 Power Power T2 0.6 0.4 0.2 0 0 0.05 0.1 Size 0.15 0.2 Supplementary Figure 7. Estimated power curves for hypotheses tests T 0 , T 1 and T 2 corrected for true size for different values of δ, n1 and n2 . Other parameters in the data generating process are fixed to νi = 0.08, ri = 0.5, σri = 0.1, i = 1, 2. 8 0.2