MICOP: Maximal information coefficient-based oscillation prediction to detect biological rhythms in proteomics data

Hitoshi Iuchi, Masahiro Sugimoto, Masaru Tomita

Circadian rhythms comprise oscillating molecular interactions, the disruption of the homeostasis of which would cause various disorders. To understand this phenomenon systematically, an accurate technique to identify oscillating molecules among omics datasets must be developed; however, this is still impeded by many difficulties, such as experimental noise and attenuated amplitude. To address these issues, we developed a new algorithm named Maximal Information Coefficient-based Oscillation Prediction (MICOP), a sine curve-matching method. The performance of MICOP in labeling oscillation or non-oscillation was compared with four reported methods using Mathews correlation coefficient (MCC) values. The numerical experiments were performed with time-series data with (1) mimicking of molecular oscillation decay, (2) high noise and low sampling frequency and (3) one-cycle data. The first experiment revealed that MICOP could accurately identify the rhythmicity of decaying molecular oscillation (MCC > 0.7). The second experiment revealed that MICOP was robust against high-level noise (MCC > 0.8) even upon the use of low-sampling-frequency data. The third experiment revealed that MICOP could accurately identify the rhythmicity of noisy one-cycle data (MCC > 0.8). As an application, we utilized MICOP to analyze time-series proteome data of mouse liver. MICOP identified that novel oscillating candidates numbered 14 and 30 for C57BL/6 and C57BL/6 J, respectively. In this paper, we presented MICOP, which is an MIC-based algorithm, for predicting periodic patterns in large-scale time-resolved protein expression profiles. The performance test using artificially generated simulation data revealed that the performance of MICOP for decaying data was superior to that of the existing widely used methods. It can reveal novel findings from time-series data and may contribute to biologically significant results. This study suggests that MICOP is an ideal approach for detecting and characterizing oscillations in time-resolved omics data sets.