Math meets biology to uncover unexpected biorhythms
When math meets biology
The researchers applied the mathematical method Antoulas used to analyze electronic digital signals to analyze a biological phenomenon, specifically gene expression data that had been collected every hour for 36 hours. The researchers analyzed more than 18,000 mouse liver genes involved in a variety of cellular processes, including metabolism, cell stress, cell cycle and cellular respiration.
“Our method revealed the fundamental cycles present in each data set collected for each gene,” Antoulas said. “We confirmed the 24-hour circadian cycles and uncovered genes whose expression over time followed a 12-hour cycle that was not evident when using other computational methods.”
“We took a closer look at the 12- and 24-hour cycles,” Dacso said. “The matrix pencil method revealed that these cycles were independent, and this has been confirmed by laboratory experiments showing that knocking down genes that follow a 24-hour cycle does not affect the expression pattern of the 12-hour genes.”
“By looking at the function of genes over time, as opposed to looking at a single moment, we have uncovered that fundamental cell functions, such as inflammation, stress response, protein quality control and energy supply, follow certain cycles,” Dacso said. “This finding has enormous implications for redefining aspects of human health as controlled by genes.”
“We and others have shown that disturbing the 24-hour clocks may lead to diseases of metabolism,” said co-author Dr. Bert O’Malley, chancellor and professor of molecular and cellular biology and Thomas C. Thompson Chair in Cell Biology at Baylor College of Medicine. “For instance, experimental evidence shows that night-shift workers who periodically change their night and day shifts or people who travel overseas often alter their sleep cycles, and this seems to make them prone to gain weight and develop diabetes and other alterations of metabolism that may lead to disease. It’s not a good idea to disturb the circadian rhythm on a regular basis. We anticipate that disturbing the other cycles may also affect health and disease.”
Other contributors to this work include Bokai Zhu, Qiang Zhang and Brian York. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, Rice University and the Max-Planck Institute for the Dynamics of Complex Technical Systems, Germany.
Financial support for this project was provided by the National Institutes of Health (NIDDK), the National Science Foundation, the American Diabetes Association, Kay and Rene Joyce Foundation and the German Science Foundation. Additional support was provided by the Max-Planck Institut für Dynamik Komplexer Technischer Systeme, Center for the Advancement of Science in Space, Brockman Medical Research Foundation, Phillip J. Carroll, Jr Professorship, Joyce Family Foundation, Sonya and William Carpenter and Peter J. Fluor Family Fund.