| Autor: |
Michael P. Menden, Richa Batra, Carsten B. Schmidt-Weber, Stefanie Eyerich, Alexander Böhner, Alexander Schäbitz, Tilo Biedermann, Nikola Müller, J. Thomas, Peter Seiringer, Natalie Garzorz-Stark, Ginte Kutkaite, Caroline Pilz, Kilian Eyerich, Sophie Roenneberg, Lam C. Tsoi, Bentolhoda Fereydouni, Johann E. Gudjonsson, F. Lauffer, M. Jargosch, Fabian Theis F |
| Rok vydání: |
2020 |
| Předmět: |
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| DOI: |
10.1101/2020.07.25.221309 |
| Popis: |
Chronic inflammatory diseases are characterized by complex interactions between genetic predisposition and tissue-specific immune responses. This heterogeneity complicates diagnoses and the ability to exploit omics approaches to improve disease management, develop more effective therapeutics, and apply precision medicine. Using skin inflammation as a model, we developed a method that integrates deep clinical phenotyping information (phenomics) with transcriptome data of lesional and non-lesional skin (564 samples) to identify clinically-relevant gene signatures. It led us to discover so-far unexplored factors, including CCAAT Enhancer-Binding Protein Beta (CEBPB) in neutrophil invasion, and Pituitary Tumor-Transforming 2 (PTTG2) in the pathogenic epithelial response to inflammation. These factors were validated using genetically-modified human skin equivalents, migration assays, and in situ imaging. Thus, by meaningful integration of deep clinical phenotyping and omics data we reveal hidden drivers of clinically-relevant biological processes. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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