CRU 303 Project Z2: Biostatistics and Systems Medicine Core Unit

State-of-the-art biostatistics and systems medicine has revolutionized the research on most complex and heterogeneous diseases. Thus, the in-depth biomathematical analysis of individual datasets and the integration of multi-dimensional datasets has enabled defining molecular networks and their significance for the pathogenesis of disease in an unbiased manner and to a degree not achievable by classical biomedical research approaches. While these approaches are now frequently applied on common diseases, such as cardiovascular disorders, and have become the driver to evolve patient care towards the precision medicine level, their application in less common diseases, including pemphigoid diseases (PDs), is still in its infancy. However, especially in these diseases with a naturally low sample size, sophisticated biomathematical/systems medicine approaches exploiting, extrapolating, and integrating all datasets available on individual patients are key to further illuminate these diseases in a cost-effective manner. To exploit these new possibilities for PDs and to ensure the most comprehensive analysis and scientific exploitation of all datasets generated in the CRU, the core unit Biostatistics & Systems Medicine (Z2-Project) was established in the 1st FP. In the 2nd FP, the Z2-Project will continue these services. Among others, it will conduct basic and mechanistic epidemiological studies and deep phenotyping of PD patients to define patient subgroups, thus uncovering the pathogenesis of PDs and contributing to the development of personalized treatment regimens. It will also identify gene variants and molecular pathways regulating PDs. In addition, it will, e.g., resolve the interactions between both the nuclear and mitochondrial genomes with the skin microbiota and their impact on PD. It will also perform a trans-ome-wide association study (transOWAS) integrating the datasets on multiple omics layers generated in the CRU with each other and with the phenomes of BP patients to establish cause-effect relationships between pathway and disease activity. This will be instrumental to identify the most promising therapeutic targets and to develop new multi-variate biomarkers for PDs. The significance of both will be subsequently experimentally/clinically addressed in the CRU projects. Conversely, the Z2-Project will also integrate experimental results from preclinical models into models to identify common subnets of PD in mice and men and their pathogenic role. Thus, collectively, the Z2-Project will be the brain of the CRU. It will be pivotal for the translation of the results of the CRU into the human situation and to elucidate the pathogenesis of PD in the ultimate model system, the patient. It will be key to finally achieve its overall aim, the establishment of a comprehensive model of the molecular processes orchestrating the effector phase of PDs, and the development of therapeutic interventions selectively interfering with these processes.