Understanding sleep and its perturbation by environment, mutation, or medication remains a central problem in biomedical research. Its examination in animal models rests on brain state analysis via classification of electroencephalographic (EEG) signatures. Traditionally, these states are classified by trained human experts by visual inspection of raw EEG recordings, which is a laborious task prone to inter-individual variability. Recently, machine learning approaches have been developed to automate this process, but their generalization capabilities are often insufficient, especially across animals from different experimental studies. To address this challenge, we crafted a convolutional neural network-based architecture to produce domain invariant predictions, and furthermore integrated a hidden Markov model to constrain state dynamics based upon known sleep physiology. Our method, which we named SPINDLE (Sleep Phase Identification with Neural networks for Domain-invariant LEearning) was validated using data of four animal cohorts from three independent sleep labs, and achieved average agreement rates of 99%, 98%, 93%, and 97% with scorings from five human experts from different labs, essentially duplicating human capability. It generalized across different genetic mutants, surgery procedures, recording setups and even different species, far exceeding state-of-the-art solutions that we tested in parallel on this task. Moreover, we show that these scored data can be processed for downstream analyzes identical to those from human-scored data, in particular by demonstrating the ability to detect mutation-induced sleep alteration. We provide to the scientific community free usage of SPINDLE and benchmarking datasets as an online server at https://sleeplearning.ethz.ch . Our aim is to catalyze high-throughput and well-standardized experimental studies in order to improve our understanding of sleep.

Sequential data often originates from diverse domains across which statistical regularities and domain specifics exist. To specifically learn cross-domain sequence representations, we introduce disentangled state space models (DSSM) -a class of SSM in which domain-invariant state dynamics is explicitly disentangled from domain-specific information governing that dynamics. We analyze how such separation can improve knowledge transfer to new domains, and enable robust prediction, sequence manipulation and domain characterization. We furthermore propose an unsupervised VAE-based training procedure to implement DSSM in form of Bayesian filters. In our experiments, we applied VAE-DSSM framework to achieve competitive performance in online ODE system identification and regression across experimental settings, and controlled generation and prediction of bouncing ball video sequences across varying gravitational influences.1 IID -independent and identically distributed.

The ability to learn disentangled representations that split underlying sources of variation in high dimensional, unstructured data is important for data efficient and robust use of neural networks. While various approaches aiming towards this goal have been proposed in recent times, a commonly accepted definition and validation procedure is missing. We provide a causal perspective on representation learning which covers disentanglement and domain shift robustness as special cases. Our causal framework allows us to introduce a new metric for the quantitative evaluation of deep latent variable models. We show how this metric can be estimated from labeled observational data and further provide an efficient estimation algorithm that scales linearly in the dataset size.

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