Probability estimation of narcolepsy type 1 in DTA mice using unlabeled EEG and EMG data.

Abstract

The manual evaluation of mouse sleep studies is labor-intensive and time-consuming. Although several approaches for automatic sleep stage classification have been proposed, no automatic pipeline for detecting a specific mouse phenotype has yet been developed. Here, we present a fully automated pipeline for estimating the probability of Narcolepsy Type 1 (NT1) in the hypocretin-tTA;TetO-Diphteria toxin A (DTA) mouse model using unlabeled electroencephalographic (EEG) and electromyographic (EMG) data. The pipeline is divided into three modules: (1) automatic sleep stage classification, (2) feature extraction, and (3) phenotype classification. We trained two automatic sleep stage classifiers, Usleep_EEG and Usleep_EMG, using data from 83 wild-type (WT) mice. We next computed features such as EEG spectral power bands, EMG root mean square, and bout metrics from 11 WT and 19 DTA mice. The features were used to train an L1-penalized logistic regression classifier in a Leave-One-Subject-Out approach, achieving an accuracy of 97%. Finally, we validated the pipeline in a held-out dataset of EEG/EMG recordings at four different timepoints during disease development in seven DTA mice, finding that the pipeline captured disease progression in all mice. While our pipeline generalizes well to data from other laboratories, it is sensitive to artifacts, which should be considered in its application. With this study, we present a pipeline that facilitates a fast assessment of NT1 probability in the DTA model and thus can accelerate large-scale evaluations of NT1 treatments.