Network integration and modelling of dynamic drug responses at multi-omics levels
| العنوان: | Network integration and modelling of dynamic drug responses at multi-omics levels |
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| المؤلفون: | Witold Wolski, Irina Agarkova, Hans Gmuender, Stefano Gotta, Ugis Sarkans, Ralf Herwig, Adrian Roth, Johannes Schuchhardt, Henrik Cordes, Patrick Guye, Bernd Timmermann, Steven A. Niederer, Jos C. S. Kleinjans, Marcha Verheijen, Jasmine Minguet, Sally J. Deeb, Carla Pluess, Vanessa Baier, Matthias Lienhard, Ivo Bachmann, Jort J. Merken, Alexandra Zerck, Stefan Boerno, Ramona Nudischer, Anne Hersey, Christoph Thiel, Francis Atkinson, Olivia Clayton, Laura Kunz, Lars Kuepfer, Fiona M. I. Hunter, Christopher F. Bauer, Stephane Heymans, Yannick Schrooders, Gal Barel, Nathalie Selevsek, Alex Lewalle, Ralph Schlapbach, Nicolas Bosc, Florian Caiment, Timo Wittenberger, Ines Smit, Bernardo Lino de Oliveira |
| المساهمون: | Toxicogenomics, RS: GROW - R1 - Prevention, RS: Carim - H02 Cardiomyopathy, Cardiologie, RS: MHeNs - R3 - Neuroscience, MUMC+: MA Med Staf Spec Cardiologie (9) |
| المصدر: | Communications Biology Communications Biology, 3(1):573. Nature Publishing Group Communications biology 3, 573 (2020). doi:10.1038/s42003-020-01302-8 Communications Biology, Vol 3, Iss 1, Pp 1-15 (2020) |
| بيانات النشر: | Nature Publishing Group UK, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Life Sciences & Biomedicine - Other Topics, Proteomics, Proteome, Medicine (miscellaneous), BIOCONDUCTOR PACKAGE, TOXICITY, Epigenesis, Genetic, 0302 clinical medicine, INDUCED HEART-FAILURE, Gene Regulatory Networks, lcsh:QH301-705.5, GENE-EXPRESSION, Protein-protein interaction networks, Mitochondria, Multidisciplinary Sciences, SEQ, Metabolome, Science & Technology - Other Topics, Data integration, General Agricultural and Biological Sciences, Life Sciences & Biomedicine, medicine.drug, Epirubicin, Signal Transduction, CARDIOTOXICITY, Sarcomeres, DOXORUBICIN, Anthracycline, Daunorubicin, Computational biology, Biology, Models, Biological, General Biochemistry, Genetics and Molecular Biology, Article, MECHANISMS, 03 medical and health sciences, ddc:570, medicine, Idarubicin, Humans, Metabolomics, Doxorubicin, Cardiotoxicity, Science & Technology, CARDIOMYOPATHY, Biochemical networks, Gene Expression Profiling, Molecular medicine, 030104 developmental biology, lcsh:Biology (General), Gene Expression Regulation, CLINICAL-PRACTICE, Transcriptome, 030217 neurology & neurosurgery |
| الوصف: | Uncovering cellular responses from heterogeneous genomic data is crucial for molecular medicine in particular for drug safety. This can be realized by integrating the molecular activities in networks of interacting proteins. As proof-of-concept we challenge network modeling with time-resolved proteome, transcriptome and methylome measurements in iPSC-derived human 3D cardiac microtissues to elucidate adverse mechanisms of anthracycline cardiotoxicity measured with four different drugs (doxorubicin, epirubicin, idarubicin and daunorubicin). Dynamic molecular analysis at in vivo drug exposure levels reveal a network of 175 disease-associated proteins and identify common modules of anthracycline cardiotoxicity in vitro, related to mitochondrial and sarcomere function as well as remodeling of extracellular matrix. These in vitro-identified modules are transferable and are evaluated with biopsies of cardiomyopathy patients. This to our knowledge most comprehensive study on anthracycline cardiotoxicity demonstrates a reproducible workflow for molecular medicine and serves as a template for detecting adverse drug responses from complex omics data. Using a network propagation approach with integrated multi-omic data, Selevsek et al. develop a reproducible workflow for identifying drug toxicity effects in cellular systems. This is demonstrated with the analysis of anthracycline cardiotoxicity in cardiac microtissues under the effect of multiple drugs. |
| وصف الملف: | Electronic; application/pdf |
| اللغة: | English |
| تدمد: | 2399-3642 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::813f559344f81693cd246f68ab1aa3b4Test http://europepmc.org/articles/PMC7567116Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....813f559344f81693cd246f68ab1aa3b4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23993642 |
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