coNfirm

Networks of heart disease: Systems medicine approach to improve heart health


Cardiovascular disease is the leading cause of death in western industrial nations. In Germany, about 40 % of all deaths are caused by diseases of the cardiovascular system. Rising life expectancy is expected to increase the appearance of cardiovascular disease.

The alliance "coNfirm" is part of the networking fonds promoted to intensify the interdisciplinary interactions between the five modules of the research and support concept "e:Med - Establishing systems medicine in Germany". coNfirm is working with conditions of cardiovascular diseases such as heart failure, myocardial infarct and atrial fibrillation. The project aims to identify disease-spanning features and mechanisms using systems medicine approaches to gain profound knowledge of cardiovascular diseases. This is essential for the development of personalized medicine, including diagnostic, preventive and therapeutic measures.

The "coNfirm" network brings together nine e:Med groups, which are combining and evaluating different experimental datasets and clinical information obtained from project partners. To facilitate an efficient data exchange, datasets are harmonized and experimental standards as well as legal requirements are created. The developed tools for combining and exchanging big datasets can be transferred to many different areas to gain more insight in this field. This knowledge will be passed on to the e:Med community in workshops.

 

Subproject 1: Multi-species and multi-level data resource

Subproject 2: Bioinformatic approaches to generate common signaling pathways of cardiac diseases

Subproject 3: Methods of data exchange within coNfirm: rules, procedures and trust

Publications

Beyes, S., Andrieux, G., Schrempp, M., Aicher, D., Wenzel, J., Anton-Garcia, P., Boerries, M. and Hecht, A. (2019). "Genome-wide mapping of DNA-binding sites identifies stemness-related genes as directly repressed targets of SNAIL1 in colorectal cancer cells." Oncogene. www.ncbi.nlm.nih.gov/pubmed/31391555.

Chakraborty, S., Andrieux, G., Hasan, A. M. M., Ahmed, M., Hosen, M. I., Rahman, T., Hossain, M. A. and Boerries, M. (2019). "Harnessing the tissue and plasma lncRNA-peptidome to discover peptide-based cancer biomarkers." Sci Rep 9(1): 12322. www.ncbi.nlm.nih.gov/pubmed/31444383.

Gross, A., Kracher, B., Kraus, J. M., Kuhlwein, S. D., Pfister, A. S., Wiese, S., Luckert, K., Potz, O., Joos, T., Van Daele, D., De Raedt, L., Kuhl, M. and Kestler, H. A. (2019). "Representing dynamic biological networks with multi-scale probabilistic models." Commun Biol 2: 21. www.ncbi.nlm.nih.gov/pubmed/30675519.

Hawe, J. S., Theis, F. J. and Heinig, M. (2019). "Inferring Interaction Networks From Multi-Omics Data." Front Genet 10: 535. www.ncbi.nlm.nih.gov/pubmed/31249591.

Heinig, M. (2018). "Using Gene Expression to Annotate Cardiovascular GWAS Loci %J Front. Cardiovasc. Med."  5. www.frontiersin.org/articles/10.3389/fcvm.2018.00059/full.

Klett, H., Jürgensen, L., Most, P., Busch, M., Günther, F., Dobreva, G., Leuschner, F., Hassel, D., Busch, H. and Boerries, M. (2018). "Delineating the Dynamic Transcriptome Response of mRNA and microRNA during Zebrafish Heart Regeneration." Biomolecules 9(1). www.ncbi.nlm.nih.gov/pubmed/30597924.

Lausser, L., Schafer, L. M., Schirra, L. R., Szekely, R., Schmid, F. and Kestler, H. A. (2019). "Assessing phenotype order in molecular data." Sci Rep 9(1): 11746. www.ncbi.nlm.nih.gov/pubmed/31409831.

Lausser, L., Siegle, L., Rottbauer, W., Frank, D., Just, S. and Kestler, H. A. (2018). "Semantic Multi-Classifier Systems Identify Predictive Processes in Heart Failure Models across Species." Biomolecules 8(4). www.ncbi.nlm.nih.gov/pubmed/30486323.

Lausser, L., Szekely, R., Kessler, V., Schwenker, F. and Kestler, H. A. (2018). Selecting Features from Foreign Classes, Springer International Publishing.

Lausser, L., Szekely, R., Klimmek, A., Schmid, F. and Kestler, H. A. (2020). "Constraining classifiers in molecular analysis: invariance and robustness." Journal of the Royal Society Interface 17(163): 14. www.ncbi.nlm.nih.gov/pubmed/32019472.

Marschner, D., Falk, M., Javorniczky, N. R., Hanke-Müller, K., Rawluk, J., Schmitt-Graeff, A., Simonetta, F., Haring, E., Dicks, S., Ku, M., Duquesne, S., Aumann, K., Rafei-Shamsabadi, D., Meiss, F., Marschner, P., Boerries, M., Negrin, R. S., Duyster, J., Zeiser, R. and Köhler, N. (2020). "MicroRNA-146a regulates immune-related adverse events caused by immune checkpoint inhibitors." JCI Insight. insight.jci.org/articles/view/132334.

Pott, A., Rottbauer, W. and Just, S. (2020). "Streamlining drug discovery assays for cardiovascular disease using zebrafish." Expert Opin Drug Discov 15(1): 27-37. www.ncbi.nlm.nih.gov/pubmed/31570020.

Pott, A., Shahid, M., Köhler, D., Pylatiuk, C., Weinmann, K., Just, S. and Rottbauer, W. (2018). "Therapeutic Chemical Screen Identifies Phosphatase Inhibitors to Reconstitute PKB Phosphorylation and Cardiac Contractility in ILK-Deficient Zebrafish." Biomolecules 8(4). www.ncbi.nlm.nih.gov/pubmed/30463267.

R Mathew, N., Vinnakota, J. M., Apostolova, P., Erny, D., Hamarsheh, S. a., Andrieux, G., Kim, J.-S., Hanke, K., Goldmann, T., Chappell-Maor, L., El-Khawanky, N., Ihorst, G., Schmidt, D., Duyster, J., Finke, J., Blank, T., Boerries, M., Blazar, B. R., Jung, S., Prinz, M. and Zeiser, R. (2020). "Graft-versus-host disease of the CNS is mediated by TNF upregulation in microglia." J. Clin. Invest. 130(3): 1315-1329. www.ncbi.nlm.nih.gov/pubmed/31846439.

Sanchez-Gonzalez, I., Bobien, A., Molnar, C., Schmid, S., Strotbek, M., Boerries, M., Busch, H. and Olayioye, M. A. (2020). "miR-149 suppresses breast cancer metastasis by blocking paracrine interactions with macrophages." Cancer Res 80(6): 1330-1341. www.ncbi.nlm.nih.gov/pubmed/31911555.

Schumacher, D., Andrieux, G., Boehnke, K., Keil, M., Silvestri, A., Silvestrov, M., Keilholz, U., Haybaeck, J., Erdmann, G., Sachse, C., Templin, M., Hoffmann, J., Boerries, M., Schafer, R. and Regenbrecht, C. R. A. (2019). "Heterogeneous pathway activation and drug response modelled in colorectal-tumor-derived 3D cultures." PLoS Genet 15(3): e1008076. www.ncbi.nlm.nih.gov/pubmed/30925167.

Schwab, J. D. and Kestler, H. A. (2018). "Automatic Screening for Perturbations in Boolean Networks." Frontiers in Physiology 9: 431. www.ncbi.nlm.nih.gov/pubmed/29740342.

Schwab, J. D., Kühlwein, S. D., Ikonomi, N., Kühl, M. and Kestler, H. A. (2020). "Concepts in Boolean network modeling: What do they all mean?" Computational and Structural Biotechnology Journal. www.sciencedirect.com/science/article/pii/S200103701930460X.

Siegle, L., Schwab, J. D., Kühlwein, S. D., Lausser, L., Tümpel, S., Pfister, A. S., Kühl, M. and Kestler, H. A. (2018). "A Boolean network of the crosstalk between IGF and Wnt signaling in aging satellite cells." PloS One 13(3): e0195126. www.ncbi.nlm.nih.gov/pubmed/29596489.