Network physiology in insomnia patients: Assessment of relevant changes in network topology with interpretable machine learning models.

Network physiology describes the human body as a complex network of interacting organ systems. It has been applied successfully to determine topological changes in different sleep stages. However, the number of network links can quickly grow above the number of parameters that are typically analyzed with standard statistical methods. Artificial Neural Networks (ANNs) are a promising approach as they are successful in large parameter spaces, such as in digital imaging. On the other hand, ANN models do not provide an intrinsic approach to interpret their predictions, and they typically require large training data sets. Both aspects are critical in biomedical research. Medical decisions need to be explainable, and large data sets of quality assured patient and control data are rare. In this paper, different models for the classification of insomnia-a common sleep disorder-have been trained with 59 patients and age and gender matched controls, based on their physiological networks. Feature relevance evaluation is employed for all methods. For ANNs, the extrinsic interpretation method DeepLift is applied. The results are not identical across methods, but certain network links have been rated as relevant by all or most of the models. While ANNs show less classification accuracy (0.89) than advanced tree-based models (0.92 and 0.93), DeepLift provides an in-depth ANN interpretation with feature relevance scores for individual data samples. The analysis revealed modifications in the pulmonar, ocular, and cerebral subnetworks that have not been described before but are consistent with known findings on the physiological impact of insomnia.

Feature relevance in physiological networks for classification of obstructive sleep apnea.

OBJECTIVE: Physiological networks (PN) model couplings between organs in a high-dimensional parameter space. Machine learning methods, in particular artifical neural networks (ANNs), are powerful on high-dimensional classification tasks. However, lack of interpretability of the resulting models has been a drawback in research. We assess relevant PN topology changes in obstructive sleep apnea (OSA) by novel ANN interpretation techniques. APPROACH: ANNs are trained to classify OSA based on the PNs of 48 patients and 48 age and gender matched healthy controls. The PNs consisting of 2812 links are derived from overnight biosignal recordings. The interpretation technique DeepLift is applied to the resulting ANN models, enabling the determination of the relevant features for classification decisions on individual subjects. The mean relevance scores of the features are compared to other machine learning methods (decision tree and random forests) and statistical tests on group differences. MAIN RESULTS: The ANN interpretation results show good agreement with the compared methods and 87% of the samples could be correctly classified. OSA patients show a significantly higher coupling (p [Formula: see text] 0.001) in light sleep (N2) between breathing rate and EEG [Formula: see text] power in all electrode locations and to chin and leg muscular tone. In deep sleep (N3), OSA leads to significantly lower coupling (p [Formula: see text] 0.01) in lateral connections of EEG [Formula: see text] and [Formula: see text] power in central and frontal positions. Misclassified OSA patients had all mild/moderate AHIs and did not show PN topology changes. Both nights of these patients have been consistently misclassified as healthy. This may indicate, that the impact of respiratory events differs in subjects, thus forming different phenotypes. SIGNIFICANCE: The proposed PN analysis provides a powerful and robust method to quantify a broad range of physiological interactions. Interpretability of the ANN make them a promising tool to identify new diagnostic markers in data-driven approaches.