Multilayer Network of Cardiovascular Diseases and Depression via Multipartite Projection

There is a significant comorbidity between cardiovascular diseases (CVD) and depression that is highly predictive of poor clinical outcome. Yet, its underlying biological pathways remain challenging to decipher, presumably due to its non-linear associations across multiple mechanisms. Mutual information provides a framework to analyze such intricacies. In this study, we proposed a multipartite projection method based on mutual information correlations to construct multilayer disease networks. We applied the method to a cross-sectional dataset from a wave of the Young Finns Study. This dataset assesses CVD and depression, along with related risk factors and two omics of biomarkers: metabolites and lipids. Instead of directly correlating CVD-related phenotypes and depressive symptoms, we extended the notion of bipartite networks to create a multipartite network that connects these phenotype and symptom variables to intermediate biological variables. Projecting from these intermediate variables results in a weighted multilayer network, where each link between CVD and depression variables is marked by its `layer' (i.e., metabolome or lipidome). Using this projection method, we identified potential mediating biomarkers that connect CVD to depression. These biomarkers thus may play significant roles in the biological pathways of CVD-depression comorbidity. Additionally, the projected network highlights sex and BMI as the most important risk factors, or confounders, associated with the comorbidity. Our method can generalize to any number of omics layers and disease phenotypes, offering a truly system-level overview of biological pathways contributing to comorbidity.