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
Andrieux, G., S. Chakraborty, T. Das and M. Boerries (2020). "Alteration of Proteotranscriptomic Landscape Reveals the Transcriptional Regulatory Circuits Controlling Key-Signaling Pathways and Metabolic Reprogramming During Tumor Evolution." Front Cell Dev Biol 8. coNfirm doi.org/10.3389/fcell.2020.586479.
Assum, I., J. Krause, M. O. Scheinhardt, C. Muller, E. Hammer, C. S. Borschel, U. Volker, L. Conradi, B. Geelhoed, T. Zeller, R. B. Schnabel and M. Heinig (2022). "Tissue-specific multi-omics analysis of atrial fibrillation." Nat Commun 13(1): 441. coNfirm www.ncbi.nlm.nih.gov/pubmed/35064145.
Bauer, C., M. Quante, W. B. Breunis, C. Regina, M. Schneider, G. Andrieux, O. Gorka, O. Groß, M. Boerries, B. Kammerer and S. Hettmer (2021). "Lack of Electron Acceptors Contributes to Redox Stress and Growth Arrest in Asparagine-Starved Sarcoma Cells." Cancers 13(3): 412. coNFirm doi.org/10.3390/cancers13030412.
Bellmann, P., L. Lausser, H. A. Kestler and F. Schwenker (2022). "A Theoretical Approach to Ordinal Classification: Feature Space-Based Definition and Classifier-Independent Detection of Ordinal Class Structures." Applied Sciences 12(4): 1815. coNfirm www.mdpi.com/2076-3417/12/4/1815.
Beyes, S., G. Andrieux, M. Schrempp, D. Aicher, J. Wenzel, P. Anton-Garcia, M. Boerries and A. Hecht (2019). "Genome-wide mapping of DNA-binding sites identifies stemness-related genes as directly repressed targets of SNAIL1 in colorectal cancer cells." Oncogene. coNfirm www.ncbi.nlm.nih.gov/pubmed/31391555.
Buhler, A., B. M. Gahr, D. D. Park, A. Bertozzi, A. Boos, M. Dalvoy, A. Pott, F. Oswald, R. A. Kovall, B. Kuhn, G. Weidinger, W. Rottbauer and S. Just (2021). "Histone deacetylase 1 controls cardiomyocyte proliferation during embryonic heart development and cardiac regeneration in zebrafish." PLoS Genet 17(11): e1009890. SYMBOL-HF & conFirm www.ncbi.nlm.nih.gov/pubmed/34723970.
Chakraborty, S., G. Andrieux, A. M. M. Hasan, M. Ahmed, M. I. Hosen, T. Rahman, M. A. Hossain and M. Boerries (2019). "Harnessing the tissue and plasma lncRNA-peptidome to discover peptide-based cancer biomarkers." Sci Rep 9(1): 12322. conFirm www.ncbi.nlm.nih.gov/pubmed/31444383.
Dicks, S., L. Jürgensen, F. Leuschner, D. Hassel, G. Andrieux and M. Boerries (2020). "Cardiac Regeneration and Tumor Growth—What Do They Have in Common?" Frontiers in Genetics 11. coNfirm doi.org/10.3389/fgene.2020.586658.
Diofano, F., K. Weinmann, I. Schneider, K. D. Thiessen, W. Rottbauer and S. Just (2020). "Genetic compensation prevents myopathy and heart failure in an in vivo model of Bag3 deficiency." Plos Genetics 16(11): 24. SYMBOL-HF & coNfirm www.ncbi.nlm.nih.gov/pubmed/33137814.
Dittman, J., T. Haydn, P. Metzger, G. A. Ward, M. Boerries, M. Vogler and S. Fulda (2020). "Next-generation hypomethylating agent SGI-110 primes acute myeloid leukemia cells to IAP antagonist by activating extrinsic and intrinsic apoptosis pathways." Cell Death Differ 27(6): 1878–1895. coNfirm doi.org/10.1038/s41418-019-0465-8.
Frey, P., A. Devisme, M. Schrempp, G. Andrieux, M. Boerries and A. Hecht (2020). "Canonical BMP Signaling Executes Epithelial-Mesenchymal Transition Downstream of SNAIL1." J Cancers 12(4): 1019. coNfirm doi.org/10.3390/cancers12041019.
Gross, A., B. Kracher, J. M. Kraus, S. D. Kuhlwein, A. S. Pfister, S. Wiese, K. Luckert, O. Potz, T. Joos, D. Van Daele, L. De Raedt, M. Kuhl and H. A. Kestler (2019). "Representing dynamic biological networks with multi-scale probabilistic models." Commun Biol 2: 21. SYMBOL-HF & coNfirm www.ncbi.nlm.nih.gov/pubmed/30675519.
Hamarsheh, S. a., L. Osswald, B. S. Saller, S. Unger, D. De Feo, J. M. Vinnakota, M. Konantz, F. M. Uhl, H. Becker, M. Lübbert, K. Shoumariyeh, C. Schürch, G. Andrieux, N. Venhoff, A. Schmitt-Graeff, S. Duquesne, D. Pfeifer, M. A. Cooper, C. Lengerke, M. Boerries, J. Duyster, C. M. Niemeyer, M. Erlacher, B. R. Blazar, B. Becher, O. Groß, T. Brummer and R. Zeiser (2020). "Oncogenic KrasG12D causes myeloproliferation via NLRP3 inflammasome activation." Nat Commun 11(1659): 1–17. CoNfirm doi.org/10.1038/s41467-020-15497-1.
Hammoud, Z. and F. Kramer (2020). "Multipath: An R Package to Generate Integrated Reproducible Pathway Models." Biology 9(12): 483. Multipath & coNfirm doi.org/10.3390/biology9120483.
Haring, E., F. M. Uhl, G. Andrieux, M. Proietti, A. Bulashevska, B. Sauer, L. M. Braun, E. de Vega Gomez, P. R. Esser, S. F. Martin, D. Pfeifer, M. Follo, A. Schmitt-Graeff, J. Buescher, J. Duyster, B. Grimbacher, M. Boerries, E. L. Pearce, R. Zeiser and P. Apostolova (2021). "Bile acids regulate intestinal antigen presentation and reduce graft-versus-host disease without impairing the graft-versus-leukemia effect." Haematologica 106(8): 2131–2146. CoNfirm doi.org/10.3324/haematol.2019.242990.
Hawe, J. S., F. J. Theis and M. Heinig (2019). "Inferring Interaction Networks From Multi-Omics Data." Front Genet 10: 535. coNfirm www.ncbi.nlm.nih.gov/pubmed/31249591.
Heinig, M. (2018). "Using Gene Expression to Annotate Cardiovascular GWAS Loci." Front. Cardiovasc. Med 5. symAtrial & conFirm www.frontiersin.org/articles/10.3389/fcvm.2018.00059/full.
Hussung, S., M. Follo, R. F. U. Klar, S. Michalczyk, K. Fritsch, F. Nollmann, J. Hipp, J. Duyster, F. Scherer, N. von Bubnoff, M. Boerries, U. Wittel and R. M. Fritsch (2020). "Development and clinical validation of discriminatory multi-target digital droplet PCR assays for the detection of hot spot KRAS and NRAS mutations in cell-free DNA." J Mol Diagn. coNfirm doi.org/10.1016/j.jmoldx.2020.04.206.
Ikonomi, N., S. D. Kuehlwein, J. D. Schwab and H. A. Kestler (2020). "Awakening the HSC: Dynamic Modeling of HSC Maintenance Unravels Regulation of the TP53 Pathway and Quiescence." Front Physiol 11(848). coNfirm doi.org/10.3389/fphys.2020.00848.
Ketterer, S., J. Mitschke, A. Ketscher, M. Schlimpert, W. Reichardt, N. Baeuerle, M. E. Hess, P. Metzger, M. Boerries, C. Peters, B. Kammerer, T. Brummer, F. Steinberg and T. Reinheckel (2020). "Cathepsin D deficiency in mammary epithelium transiently stalls breast cancer by interference with mTORC1 signaling." Nat Commun 11(5133): 1–18. coNfirm doi.org/10.1038/s41467-020-18935-2.
Kläsener, K., J. Jellusova, G. Andrieux, U. Salzer, C. Böhler, S. N. Steiner, J. B. Albinus, M. Cavallari, B. Süß, R. E. Voll, M. Boerries, B. Wollscheid and M. Reth (2021). "CD20 as a gatekeeper of the resting state of human B cells." Proc Natl Acad Sci U.S.A 118(7): e2021342118. coNfirm doi.org/10.1073/pnas.2021342118.
Klett, H., L. Jürgensen, P. Most, M. Busch, F. Günther, G. Dobreva, F. Leuschner, D. Hassel, H. Busch and M. Boerries (2018). "Delineating the Dynamic Transcriptome Response of mRNA and microRNA during Zebrafish Heart Regeneration." Biomolecules 9(1). DeCaRe & coNfirm doi.org/10.3390/biom9010011.
Kozyra, E. J., V. B. Pastor, S. Lefkopoulos, S. S. Sahoo, H. Busch, R. K. Voss, M. Erlacher, D. Lebrecht, E. A. Szvetnik, S. Hirabayashi, R. Pasaulienė, L. Pedace, M. Tartaglia, C. Klemann, P. Metzger, M. Boerries, A. Catala, H. Hasle, V. de Haas, K. Kállay, R. Masetti, B. De Moerloose, M. Dworzak, M. Schmugge, O. Smith, J. Starý, E. Mejstrikova, M. Ussowicz, E. Morris, P. Singh, M. Collin, M. Derecka, G. Göhring, C. Flotho, B. Strahm, F. Locatelli, C. M. Niemeyer, E. Trompouki, M. W. Wlodarski and E. W. G. o. M. i. Childhood (2020). "Synonymous GATA2 mutations result in selective loss of mutated RNA and are common in patients with GATA2 deficiency." Leukemia: 1–15. coNfirm doi.org/10.1038/s41375-020-0899-5.
Lausser, L., L. M. Schäfer, S. D. Kühlwein, A. M. R. Kestler and H. A. Kestler (2020). "Detecting Ordinal Subcascades." Neural Process Lett 52(3): 2583–2605. coNfirm doi.org/10.1007/s11063-020-10362-0.
Lausser, L., L. M. Schafer, L. R. Schirra, R. Szekely, F. Schmid and H. A. Kestler (2019). "Assessing phenotype order in molecular data." Sci Rep 9(1): 11746. coNfirm & SYMBOL-HF www.ncbi.nlm.nih.gov/pubmed/31409831.
Lausser, L., L. Siegle, W. Rottbauer, D. Frank, S. Just and H. A. Kestler (2018). "Semantic Multi-Classifier Systems Identify Predictive Processes in Heart Failure Models across Species." Biomolecules 8(4). SYMBOL-HF & coNfirm www.ncbi.nlm.nih.gov/pubmed/30486323.
Lausser, L., R. Szekely, V. Kessler, F. Schwenker and H. A. Kestler (2018). Selecting Features from Foreign Classes, Springer International Publishing.
Lausser, L., R. Szekely and H. A. Kestler (2020). "Chained correlations for feature selection." Advances in Data Analysis and Classification: 1–14. coNfirm ideas.repec.org/a/spr/advdac/vyid10.1007_s11634-020-00397-5.html.
Lausser, L., R. Szekely, A. Klimmek, F. Schmid and H. A. Kestler (2020). "Constraining classifiers in molecular analysis: invariance and robustness." Journal of the Royal Society Interface 17(163): 14. coNfirm www.ncbi.nlm.nih.gov/pubmed/32019472.
Maccari, M. E., S. Fuchs, P. Kury, G. Andrieux, S. Völkl, B. Bengsch, M. R. Lorenz, M. Heeg, J. Rohr, S. Jägle, C. N. Castro, M. Groß, U. Warthorst, C. König, I. Fuchs, C. Speckmann, J. Thalhammer, F. G. Kapp, M. G. Seidel, G. Dückers, S. Schönberger, C. Schütz, M. Führer, R. Kobbe, D. Holzinger, C. Klemann, P. Smisek, S. Owens, G. Horneff, R. Kolb, N. Naumann-Bartsch, M. Miano, J. Staniek, M. Rizzi, T. Kalina, P. Schneider, A. Erxleben, R. Backofen, A. Ekici, C. M. Niemeyer, K. Warnatz, B. Grimbacher, H. Eibel, A. Mackensen, A. P. Frei, K. Schwarz, M. Boerries, S. Ehl and A. Rensing-Ehl (2021). "A distinct CD38+CD45RA+ population of CD4+, CD8+, and double-negative T cells is controlled by FAS." J Exp Med 218(2). coNfirm doi.org/10.1084/jem.20192191.
Marschner, D., M. Falk, N. R. Javorniczky, K. Hanke-Müller, J. Rawluk, A. Schmitt-Graeff, F. Simonetta, E. Haring, S. Dicks, M. Ku, S. Duquesne, K. Aumann, D. Rafei-Shamsabadi, F. Meiss, P. Marschner, M. Boerries, R. S. Negrin, J. Duyster, R. Zeiser and N. Köhler (2020). "MicroRNA-146a regulates immune-related adverse events caused by immune checkpoint inhibitors." JCI Insight 5(6). coNfirm insight.jci.org/articles/view/132334.
Martinez-Hernandez, J. E., Z. Hammoud, A. M. de Sousa, F. Kramer, R. L. do Monte-Neto, V. Maracaja-Coutinho and A. J. M. Martin (2021). "Network-Based Approaches Reveal Potential Therapeutic Targets for Host-Directed Antileishmanial Therapy Driving Drug Repurposing." Microbiology Spectrum 9(2). MultiPath & coNfirm journals.asm.org/doi/10.1128/Spectrum.01018-21.
Müller, A., L. Lausser, A. Wilhelm, T. Ropinski, M. Platzer, H. Neumann and H. A. Kestler (2020). "A perceptually optimised bivariate visualisation scheme for high-dimensional fold-change data." Adv Data Anal Classif: 1–18. coNfirm doi.org/10.1007/s11634-020-00416-5.
Norona, J., P. Apostolova, D. Schmidt, R. Ihlemann, N. Reischmann, G. Taylor, N. Köhler, J. de Heer, S. Heeg, G. Andrieux, B. A. Siranosian, A. Schmitt-Graeff, D. Pfeifer, A. Catalano, I. Frew, M. Proietti, B. Grimbacher, A. Bulashevska, A. S. Bhatt, T. Brummer, T. S. Clauditz, T. Zabelina, N. Kroeger, B. R. Blazar, M. Boerries, F. Ayuk and R. Zeiser (2020). "Glucagon like peptide-2 for Intestinal stem cell and Paneth cell repair during graft-versus-host disease in mice and humans." Blood. coNfirm doi.org/10.1182/blood.2020005957.
Osswald, L., S. a. Hamarsheh, F. M. Uhl, G. Andrieux, C. Klein, C. Dierks, S. Duquesne, L. M. Braun, A. Schmitt-Graeff, J. Duyster, M. Boerries, T. Brummer and R. Zeiser (2021). "Oncogenic KrasG12D Activation in the Nonhematopoietic Bone Marrow Microenvironment Causes Myelodysplastic Syndrome in Mice." Mol Cancer Res 19(9): 1596–1608. CoNfirm doi.org/10.1158/1541-7786.MCR-20-0275.
Park, D.-D., B. M. Gahr, J. Krause, W. Rottbauer, T. Zeller and S. Just (2021). "Long-Chain Acyl-Carnitines Interfere with Mitochondrial ATP Production Leading to Cardiac Dysfunction in Zebrafish." Int J Mol Sci 22(16): 8468. SYMBOL-HF & coNfirm doi.org/10.3390/ijms22168468.
Pott, A., W. Rottbauer and S. Just (2020). "Streamlining drug discovery assays for cardiovascular disease using zebrafish." Expert Opin Drug Discov 15(1): 27-37. coNfirm & SYMBOL-HF www.ncbi.nlm.nih.gov/pubmed/31570020.
Pott, A., M. Shahid, D. Köhler, C. Pylatiuk, K. Weinmann, S. Just and W. Rottbauer (2018). "Therapeutic Chemical Screen Identifies Phosphatase Inhibitors to Reconstitute PKB Phosphorylation and Cardiac Contractility in ILK-Deficient Zebrafish." Biomolecules 8(4). SYMBOL-HF & coNfirm doi.org/10.3390/biom8040153.
R Mathew, N., J. M. Vinnakota, P. Apostolova, D. Erny, S. a. Hamarsheh, G. Andrieux, J.-S. Kim, K. Hanke, T. Goldmann, L. Chappell-Maor, N. El-Khawanky, G. Ihorst, D. Schmidt, J. Duyster, J. Finke, T. Blank, M. Boerries, B. R. Blazar, S. Jung, M. Prinz and R. Zeiser (2020). "Graft-versus-host disease of the CNS is mediated by TNF upregulation in microglia." J. Clin. Invest. 130(3): 1315-1329. coNfirm www.ncbi.nlm.nih.gov/pubmed/31846439.
Rattka, M., S. Westphal, B. M. Gahr, S. Just and W. Rottbauer (2021). "Spen deficiency interferes with Connexin 43 expression and leads to heart failure in zebrafish." Journal of Molecular and Cellular Cardiology 155: 25-35. SYMBOL-HF & coNfirm doi.org/10.1016/j.yjmcc.2021.01.006.
Reischmann, N., G. Andrieux, R. Griffin, T. Reinheckel, M. Boerries and T. Brummer (2020). "BRAFV600E drives dedifferentiation in small intestinal and colonic organoids and cooperates with mutant p53 and Apc loss in transformation." Oncogene: 1–18. coNfirm doi.org/10.1038/s41388-020-01414-9.
Saleva-Stateva, M., M. Hess, K. Technau-Hafsi, L. Weibel, M.-A. Badea, M. d. C. Boente, M. Theiler, M. J. Fiandrino, P. Hoeger, A. Zimmer, D. Rafei-Shamsabadi, M. Balabanova, J. Fischer, M. Boerries and C. Has (2021). "Molecular characterization and natural history of linear porokeratosis: A case series." Journal of the American Academy of Dermatology 85(6): 1603–1606. CoNfirm doi.org/10.1016/j.jaad.2020.11.061.
Sanchez-Gonzalez, I., A. Bobien, C. Molnar, S. Schmid, M. Strotbek, M. Boerries, H. Busch and M. A. Olayioye (2020). "miR-149 suppresses breast cancer metastasis by blocking paracrine interactions with macrophages." Cancer Res 80(6): 1330-1341. coNfirm www.ncbi.nlm.nih.gov/pubmed/31911555.
Schumacher, D., G. Andrieux, K. Boehnke, M. Keil, A. Silvestri, M. Silvestrov, U. Keilholz, J. Haybaeck, G. Erdmann, C. Sachse, M. Templin, J. Hoffmann, M. Boerries, R. Schafer and C. R. A. Regenbrecht (2019). "Heterogeneous pathway activation and drug response modelled in colorectal-tumor-derived 3D cultures." PLoS Genet 15(3): e1008076. coNfirm www.ncbi.nlm.nih.gov/pubmed/30925167.
Schwab, J. D. and H. A. Kestler (2018). "Automatic Screening for Perturbations in Boolean Networks." Frontiers in Physiology 9: 431. coNfirm & SYMBOL-HF www.ncbi.nlm.nih.gov/pubmed/29740342.
Schwab, J. D., S. D. Kühlwein, N. Ikonomi, M. Kühl and H. A. Kestler (2020). "Concepts in Boolean network modeling: What do they all mean?" Computational and Structural Biotechnology Journal. coNfirm www.sciencedirect.com/science/article/pii/S200103701930460X.
Seifert, S., S. Gundlach, O. Junge and S. Szymczak (2020). "Integrating biological knowledge and gene expression data using pathway guided random forests: A benchmarking study." Bioinformatics. ComorbSysMed & coNfirm doi.org/10.1093/bioinformatics/btaa483.
Siegle, L., J. D. Schwab, S. D. Kühlwein, L. Lausser, S. Tümpel, A. S. Pfister, M. Kühl and H. A. Kestler (2018). "A Boolean network of the crosstalk between IGF and Wnt signaling in aging satellite cells." PloS One 13(3): e0195126. coNfirm & SYMBOL-HF www.ncbi.nlm.nih.gov/pubmed/29596489.
Thiam, P., H. Hihn, D. A. Braun, H. A. Kestler and F. Schwenker (2021). "Multi-Modal Pain Intensity Assessment Based on Physiological Signals: A Deep Learning Perspective." Front Physiol 12: 720464. CoNfirm www.ncbi.nlm.nih.gov/pubmed/34539444.
Thiam, P., H. Kestler and F. Schwenker (2020). Multimodal Deep Denoising Convolutional Autoencoders for Pain Intensity Classification based on Physiological Signals - ICPRAM 2020. ICPRAM 2020 - 9th International Conference on Pattern Recognition Applications and Methods, Proceedings of the 9th International Conference on Pattern Recognition Applications and Methods (ICPRAM 2020).
Thiam, P., H. A. Kestler and F. Schwenker (2020). "Two-Stream Attention Network for Pain Recognition from Video Sequences." SENSORS 20(3). coNfirm doi.org/10.3390/s20030839.
Uhl, F. M., S. Chen, D. O’Sullivan, J. Edwards-Hicks, G. Richter, E. Haring, G. Andrieux, S. Halbach, P. Apostolova, J. Büscher, S. Duquesne, W. Melchinger, B. Sauer, K. Shoumariyeh, A. Schmitt-Graeff, M. Kreutz, M. Lübbert, J. Duyster, T. Brummer, M. Boerries, T. Madl, B. R. Blazar, O. Groß, E. L. Pearce and R. Zeiser (2020). "Metabolic reprogramming of donor T cells enhances graft-versus-leukemia effects in mice and humans." Sci Transl Med 12(567): eabb8969. coNfirm doi.org/10.1126/scitranslmed.abb8969.
Völkel, G., S. Laban, A. Fürstberger, S. D. Kühlwein, N. Ikonomi, T. K. Hoffman, C. Brunner, D. S. Neuberg, V. Gaidzik, H. Döhner, J. M. Kraus and H. A. Kestler (2021). "Analysis, identification and visualization of subgroups in genomics." Briefings Bioinf 22(3). coNfirm doi.org/10.1093/bib/bbaa217.
Weidner, F. M., J. D. Schwab, S. D. Werle, N. Ikonomi, L. Lausser and H. A. Kestler (2021). "Capturing dynamic relevance in Boolean networks using graph theoretical measures." Bioinformatics. coNfirm www.ncbi.nlm.nih.gov/pubmed/33983406.
Wenzel, J., K. Rose, E. B. Haghighi, C. Lamprecht, G. Rauen, V. Freihen, R. Kesselring, M. Boerries and A. Hecht (2020). "Loss of the nuclear Wnt pathway effector TCF7L2 promotes migration and invasion of human colorectal cancer cells." Oncogene: 1–17. coNfirm doi.org/10.1038/s41388-020-1259-7.
Werle, S. D., J. D. Schwab, M. Tatura, S. Kirchhoff, R. Szekely, R. Diels, N. Ikonomi, B. Sipos, J. Sperveslage, T. M. Gress, M. Buchholz and H. A. Kestler (2021). "Unraveling the Molecular Tumor-Promoting Regulation of Cofilin-1 in Pancreatic Cancer." Cancers 13(4): 725. SYMBOL-HF, conFirm doi.org/10.3390/cancers13040725.