Integration of genome-scale data identifies candidate sleep regulators

Study Objectives Genetics impacts sleep, yet, the molecular mechanisms underlying sleep regulation remain elusive. In this study, we built machine learning models to predict sleep genes based on their similarity to genes that are known to regulate sleep. Methods We trained a prediction model on thousands of published datasets, representing circadian, immune, sleep deprivation, and many other processes, using a manually curated list of 109 sleep genes. Results Our predictions fit with prior knowledge of sleep regulation and identified key genes and pathways to pursue in follow-up studies. As an example, we focused on the NF-kappa B pathway and showed that chronic activation of NF-kappa B in a genetic mouse model impacted the sleep-wake patterns. Conclusion Our study highlights the power of machine learning in integrating prior knowledge and genome-wide data to study genetic regulation of complex behaviors such as sleep.