AUTHOR=Gharagozloo Marjan , Amrani Abdelaziz , Wittingstall Kevin , Hamilton-Wright Andrew , Gris Denis TITLE=Machine Learning in Modeling of Mouse Behavior JOURNAL=Frontiers in Neuroscience VOLUME=Volume 15 - 2021 YEAR=2021 URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2021.700253 DOI=10.3389/fnins.2021.700253 ISSN=1662-453X ABSTRACT=Mouse behavior is a primary outcome in evaluations of therapeutic efficacy. Exhaustive, continuous, multiparametric behavioral phenotyping is a valuable tool for understanding the pathophysiological status of mouse brain diseases. Previously, we showed that analysis of continuous mouse recording could reveal the impact of inflammation on behavioral outcomes. In this study, we sought to predict the physiological states of mice using sequential and temporal patterns of behavior generated by home cage-based automated behavioral platforms. We hypothesized that behavioral patterns within short time windows are reflective of physiological state, and that computer modeling of mouse behavioral routines can serve as a predictive tool in classification tasks. To remove bias due to researcher decisions, our data flow is indifferent to the quality, value, and importance of any given feature in isolation. To classify day and night behavior, as an example application, we developed a data preprocessing flow and utilized logistic regression (LG), support vector machines (SVM), random forest (RF), and one-dimensional convolutional neural networks paired with long short-term memory deep neural networks (1DConvBiLSTM). We determined that a 5-minute video clip is sufficient to classify mouse behavior with high accuracy. LG, SVM, and RF performed similarly, predicting mouse behavior with 85% accuracy, and combining the three algorithms in an ensemble procedure increased accuracy to 90%. The best performance was achieved by combining the 1DConv and BiLSTM algorithms yielding 96% accuracy. Our findings demonstrate that computer modeling of the home-cage ethome can clearly define mouse physiological state. Furthermore, we showed that continuous behavioral data can be analyzed using approaches similar to natural language processing. These data provide proof of concept for future research in diagnostics of complex pathophysiological changes that are accompanied by changes in behavioral profile.