GB-XMAP

Development of a system-theoretical methodology to characterize altered gene expression in neuropsychiatric diseases and inflammatory bowel diseases

Disordered communication between the gut and the brain can promote the development of neuropsychiatric and inflammatory bowel diseases. The aim of the GB-XMAP research network is to elucidate the disease-relevant molecular mechanisms that are common between schizophrenia and ulcerative colitis, as well as to develop a systems medicine model of potential dysfunction of the gut-brain axis. Well-characterized molecular genetic risk factors, relevant for both diseases, should be considered for this purpose. Therefore, RNA sequencing data from more than 1.000 patients and 1.500 healthy control individuals are collected and evaluated using genetic datasets of known genome-wide association studies. The datasets are combined to a disease-spanning interaction map by using bioinformatic methods and mathematical modeling techniques.

The specific aim is to identify relevant target genes and molecular mechanisms, which could be the basis to develop effective therapies for mental illness and inflammatory bowel diseases in laboratory experiments.

The GB-XMAP research network intends to establish a new disease-spanning network alliance within the research and funding concept "e:Med - Establishing systems medicine in Germany". This alliance consists of working groups from the e:Med research consortia "SysINFLAME" (inflammatory research) and "IntegraMent" (neuropsychiatric diseases) as well as the research group "de.NBI-SysBio" (Systems-biological Modeling) of the German Network for Bioinformatics. As a result, this alliance contributes to an intensive interdisciplinary crosslinking of systems medicine research groups.

Publications

Degenhardt, F., Wendorff, M., Wittig, M., Ellinghaus, E., Datta, L. W., Schembri, J., Ng, S. C., Rosati, E., Hubenthal, M., Ellinghaus, D., Jung, E. S., Lieb, W., Abedian, S., Malekzadeh, R., Cheon, J. H., Ellul, P., Sood, A., Midha, V., Thelma, B. K., Wong, S. H., Schreiber, S., Yamazaki, K., Kubo, M., Boucher, G., Rioux, J. D., Lenz, T. L., Brant, S. R. and Franke, A. (2019). "Construction and benchmarking of a multi-ethnic reference panel for the imputation of HLA class I and II alleles." Hum Mol Genet 28(12): 2078-2092. www.ncbi.nlm.nih.gov/pubmed/30590525.

Mucha, S., Baurecht, H., Novak, N., Rodríguez, E., Bej, S., Mayr, G., Emmert, H., Stölzl, D., Gerdes, S., Jung, E. S., Degenhardt, F., Hübenthal, M., Ellinghaus, E., Kässens, J. C., Wienbrandt, L., Lieb, W., Müller-Nurasyid, M., Hotze, M., Dand, N., Grosche, S., Marenholz, I., Arnold, A., Homuth, G., Schmidt, C. O., Wehkamp, U., Nöthen, M. M., Hoffmann, P., Paternoster, L., Standl, M., Bønnelykke, K., Ahluwalia, T. S., Bisgaard, H., Peters, A., Gieger, C., Waldenberger, M., Schulz, H., Strauch, K., Werfel, T., Lee, Y.-A., Wolfien, M., Rosenstiel, P., Wolkenhauer, O., Schreiber, S., Franke, A., Weidinger, S. and Ellinghaus, D. (2020). "Protein-coding variants contribute to the risk of atopic dermatitis and skin-specific gene expression." JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 145(4): 1208–1218. doi.org/10.1016/j.jaci.2019.10.030.

Shadrin, A. A., Mucha, S., Ellinghaus, D., Makarious, M. B., Blauwendraat, C., Sreelatha, A. A. K., Heras-Garvin, A., Ding, J., Hammer, M., Foubert-Samier, A., Meissner, W. G., Rascol, O., Pavy-Le Traon, A., Frei, O., O'Connell, K. S., Bahrami, S., Schreiber, S., Lieb, W., Muller-Nurasyid, M., Schminke, U., Homuth, G., Schmidt, C. O., Nothen, M. M. and Hoffmann, P. (2020). "Shared Genetics of Multiple System Atrophy and Inflammatory Bowel Disease." MOVEMENT DISORDERS. doi.org/10.1002/mds.28338.

Uellendahl-Werth, F., Wolfien, M., Franke, A., Wolkenhauer, O. and Ellinghaus, D. (2020). "A benchmark of hemoglobin blocking during library preparation for mRNA-Sequencing of human blood samples." Scientific Reports 10(5630): 1–10. doi.org/10.1038/s41598-020-62637-0.

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