Bioinformatics profiling identifies a new mammalian clock gene

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Over the last few decades researchers have characterized a set of clock genes that drive daily rhythms of physiology and behavior in all types of species, from flies to humans. Over 15 mammalian clock proteins have been identified, but researchers surmise there are more. A team from the Perelman School of Medicine at the University of Pennsylvania wondered if big-data approaches could find them.To accelerate clock-gene discovery, the investigators, led by John Hogenesch, PhD, professor of Pharmacology and first author Ron Anafi, MD, PhD, an instructor in the department of Medicine, used a computer-assisted approach to identify and rank candidate clock components. This approach found a new core clock gene, which the team named CHRONO. Their findings appear this week in PLOS Biology.Hogenesch likens their approach to online profiling of movie suggestions for customers: “Think of Netflix. Based on your personalized movie profile, it predicts what movies you may want to watch in the future based on what you watched in the past.” He thought the team could use this approach to identify new clock genes, given criteria already established from the “behavior” of known clock genes identified in the past two decades:Clock genes cause oscillations at the messenger RNA and protein level. Clock proteins physically interact with other clock proteins to form complexes that control daily rhythm inside cells. Disruption of clock genes in cell models cause changes in observable behavioral and metabolic traits on a 24-hour cycle. Clock genes are conserved across 600 million years of evolution from fruitflies to humans. “We used a simple form of machine learning to integrate biologically relevant, genome-scale data and ranked genes based on their similarity to known clock proteins,” explains Hogenesch. …


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