SP3 - SYMPATH

Systems-medical analysis and modelling of pneumonia-aggravated atherosclerosis

In SP3 of the SYMPATH consortium we combine comprehensive clinical and epidemiological data with time-series data of mice experiments to develop a systems-biological understanding of pneumonia-aggravated atherosclerosis. We aim at constructing models to simulate the effects of different therapeutic and preventive measures in order to develop improved treatment and surveillance strategies for pneumonia patients.
We first perform comprehensive analyses of the clinical and epidemiological data of several cohorts, which are available through SP1 and which will be completed in the framework of the project. Specifically, we analyze the relationships among several omics layers including genetics, transcriptomics, lipidomics, metabolomics and cytokines and their relationships to clinical cross-sectional and longitudinal outcomes. By this approach, we aim at identifying causal mechanisms which are of relevance for the disease course. Then, these mechanisms will be incorporated into the developed mechanistic models. We also plan to validate identified causal relationships in animal experiments in SP2.
In parallel, we develop mechanistic differential equations models of pneumonia-aggravated atherosclerosis in mice. These models will be built as extensions of already established models of local and systemic inflammation during pneumonia. Based on the time-series data developed in SP2, we will derive suitable model assumptions and will calibrate the model. Conversely, model predictions can be validated in additional experiments.  We plan a step-wise model-building process including inflammation, formation and progression of atherosclerotic lesions and stability of plaques considering risk factors. Using the identified causal relationships in humans, we plan to translate the model to the human situation and to calibrate it on the basis of follow-up data collected in SP1.