Alternative splicing (AS) is a biological mechanism that allows to create different transcripts from the same DNA sequence. The overall goal of Sys_CARE is to investigate for the first time the importance of AS for the pathogenesis and the disease process with system medicine approaches and to develop the required bioinformatic methods.

To this end, we have access to a large dataset of molecular and clinical data, which will be complemented in the course of this project.

In the course of the digital revolution, the use and processing of personal data has become important for the overall value chain. In this context, it is vital to ensure a balance of interests among all stakeholders. While business and research are interested in a smooth exchange of data, the people providing data want above all to preserve their data sovereignty in terms of data protection law and data ethics. One key to reducing the threat of asymmetries lies in the involvement of data trustees, i.e. neutral intermediaries.

In order to establish data trustees in the long term, a legal regulatory framework is needed that guarantees data protection and at the same time creates incentives to promote innovation. TreuMed is taking up this challenge. We develop and test data trustee models and corresponding business concepts using the example of "distributed artificial intelligence" in medicine. Machine learning methods in medical research rely on extensive, sensitive patient data to be able to make reliable predictions. However, strict data protection can counteract the success of research because it reduces the amount of data available.

Within the framework of the German Center for Cardiovascular Diseases, protein, mRNA and miRNA analyses of patient samples are performed to contribute to a better understanding of pathomechanisms of cardiovascular diseases or of molecular changes during therapy. The focus is on dilated cardiomyopathy (DCM). This myocardial disease is characterized by a decrease in contractile function of the myocardium and by dilatation of the right and left ventricle.

Overall, however, the importance of heart failure (HI) with its etiologically very different causes is growing, and with it the need for better diagnostics and the development of improved therapeutic approaches. A prerequisite for this is the investigation of samples in existing and newly established patient cohorts for a better understanding of the molecular adaptations in HI.

Thus, the goal of this work is to detect differences in RNA and protein patterns in both tissues and biofluids of HI patients and control patients without impaired cardiac function by screening biospecimens. Diagnostic molecular signatures will be used to classify patient subgroups and enable therapy adjustments based on prediction of disease progression.

Cells secrete proteins that play an important role in maintaining cell integrity and stability, mobilisation and differentiation. Such proteins can act as autocrine (effect on cells of the same type) or paracrine (effect on other cell types) factors and indirectly initiate a cell response to external stimuli. The analysis of secreted proteins, also from cell cultures, requires special workflows that take into account the small amount of these protein species, their presence in low concentrations and interference with medium components. In the working group, adapted cell culture protocols and protein enrichment strategies have been established that enable a comprehensive mass spectrometric analysis of secretomes even from low cell numbers such as those present in stem cells.