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  Network integration and modelling of dynamic drug responses at multi-omics levels

Selevsek, N., Caiment, F., Nudischer, R., Gmuender, H., Agarkova, I., Atkinson, F. L., et al. (2020). Network integration and modelling of dynamic drug responses at multi-omics levels. Communications Biology, 3: 573. doi:10.1038/s42003-020-01302-8.

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Selevsek, Nathalie , Author
Caiment, Florian , Author
Nudischer, Ramona , Author
Gmuender, Hans, Author
Agarkova, Irina , Author
Atkinson, Francis L. , Author
Bachmann, Ivo, Author
Baier, Vanessa, Author
Barel, Gal1, Author              
Bauer, Chris, Author
Boerno, Stefan2, Author              
Bosc, Nicolas , Author
Clayton, Olivia , Author
Cordes, Henrik, Author
Deeb, Sally , Author
Gotta, Stefano , Author
Guye, Patrick , Author
Hersey, Anne , Author
Hunter, Fiona M. I. , Author
Kunz, Laura, Author
Lewalle, Alex , AuthorLienhard, Matthias1, Author              Merken, Jort, AuthorMinguet, Jasmine , AuthorOliveira, Bernardo , AuthorPluess, Carla, AuthorSarkans, Ugis , AuthorSchrooders, Yannick , AuthorSchuchhardt, Johannes , AuthorSmit, Ines, AuthorThiel, Christoph , AuthorTimmermann, Bernd2, Author              Verheijen, Marcha , AuthorWittenberger, Timo, AuthorWolski, Witold , AuthorZerck, Alexandra, AuthorHeymans, Stephane , AuthorKuepfer, Lars, AuthorRoth, Adrian, AuthorSchlapbach, Ralph , AuthorNiederer, Steven , AuthorHerwig, Ralf1, Author              Kleinjans, Jos, Author more..
Affiliations:
1Bioinformatics (Ralf Herwig), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2385701              
2Sequencing (Head: Bernd Timmermann), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479670              

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 Abstract: 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.

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Language(s): eng - English
 Dates: 2020-09-142020-10-15
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1038/s42003-020-01302-8
 Degree: -

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Title: Communications Biology
Source Genre: Journal
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Publ. Info: London : Springer Nature
Pages: - Volume / Issue: 3 Sequence Number: 573 Start / End Page: - Identifier: ISSN: 2399-3642
CoNE: https://pure.mpg.de/cone/journals/resource/2399-3642