From heterogeneous healthcare data to disease-specific biomarker networks: A hierarchical Bayesian network approach

In this work, we introduce an entirely data-driven and automated approach to reveal disease-associated biomarker and risk factor networks from heterogeneous and high-dimensional healthcare data. Our workflow is based on Bayesian networks, which are a popular tool for analyzing the interplay of biomarkers. Usually, data require extensive manual preprocessing and dimension reduction to allow for effective learning of Bayesian networks. For heterogeneous data, this preprocessing is hard to automatize and typically requires domain-specific prior knowledge. We here combine Bayesian network learning with hierarchical variable clustering in order to detect groups of similar features and learn interactions between them entirely automated. We present an optimization algorithm for the adaptive refinement of such group Bayesian networks to account for a specific target variable, like a disease. The combination of Bayesian networks, clustering, and refinement yields low-dimensional but disease-specific interaction networks. These networks provide easily interpretable, yet accurate models of biomarker interdependencies. We test our method extensively on simulated data, as well as on data from the Study of Health in Pomerania (SHIP-TREND), and demonstrate its effectiveness using non-alcoholic fatty liver disease and hypertension as examples. We show that the group network models outperform available biomarker scores, while at the same time, they provide an easily interpretable interaction network.Author summary: High-dimensional and heterogeneous healthcare data, such as electronic health records or epidemiological study data, contain much information on yet unknown risk factors that are associated with disease development. The identification of these risk factors may help to improve prevention, diagnosis, and therapy. Bayesian networks are powerful statistical models that can decipher these complex relationships. However, high dimensionality and heterogeneity of data, together with missing values and high feature correlation, make it difficult to automatically learn a good model from data. To facilitate the use of network models, we present a novel, fully automated workflow that combines network learning with hierarchical clustering. The algorithm reveals groups of strongly related features and models the interactions among those groups. It results in simpler network models that are easier to analyze. We introduce a method of adaptive refinement of such models to ensure that disease-relevant parts of the network are modeled in great detail. Our approach makes it easy to learn compact, accurate, and easily interpretable biomarker interaction networks. We test our method extensively on simulated data as well as data from the Study of Health in Pomerania (SHIP-Trend) by learning models of hypertension and non-alcoholic fatty liver disease.