A new regulatory interaction suggested by simulations for circadian genetic control mechanism in mammals

Knowledge of molecular biological systems is increasing at an amazing pace. It is becoming harder to intuitively evaluate the significance of each interaction between the molecules of the complex biological systems. Hence, we need to develop an efficient computational method to explore the biological mechanisms. In this study, we employed a hybrid functional Petri net in order to analyze mammalian circadian genetic control mechanisms, which consists of feedback loops of clock genes and generates endogenous near 24 h rhythms in mammals. We constructed a computational model based on the available biological data, and by using Genomic Object Net, we performed computer simulations of the time courses of clock gene transcription and translation. Although the original model successfully reproduced most of the circadian genetic control mechanisms, two discrepancies remained despite a wide selection of the parameters. We found that addition of a hypothetical path into the original model result in successful simulation of time courses and phase relationships among clock genes. This also demonstrates the usefulness of the hybrid functional Petri net approach to biological systems.