A shift of dynamic equilibrium between the KIT active and inactive states causes drug resistance.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
AbstractIntegrative bioinformatics is an emerging field in the big data era, offering a steadily increasing number of algorithms and analysis tools. However, for researchers in experimental life sciences it is often difficult to follow and properly apply the bioinformatical methods in order to unravel the complexity and systemic effects of omics data. Here, we present an integrative bioinformatics pipeline to decipher crucial biological insights from global transcriptome profiling data to validate innovative therapeutics. It is available as a web application for an interactive and simplified analysis without the need for programming skills or deep bioinformatics background. The approach was applied to an ex vivo cardiac model treated with natural anti-fibrotic compounds and we obtained new mechanistic insights into their anti-fibrotic action and molecular interplay with miRNAs in cardiac fibrosis. Several gene pathways associated with proliferation, extracellular matrix processes and wound healing were altered, and we could identify micro (mi) RNA-21-5p and miRNA-223-3p as key molecular components related to the anti-fibrotic treatment. Importantly, our pipeline is not restricted to a specific cell type or disease and can be broadly applied to better understand the unprecedented level of complexity in big data research.
CitationProteins. 2020;10.1002/prot.25963. doi:10.1002/prot.25963.
AffiliationHIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International
- Molecular mechanism of D816X mutation-induced c-Kit activation and -mediated inhibitor resistance in gastrointestinal stromal tumor.
- Authors: Jiang H, Shao W, Wang Y, Xu R, Zhou L, Mu X
- Issue date: 2018 Sep
- Mutation D816V alters the internal structure and dynamics of c-KIT receptor cytoplasmic region: implications for dimerization and activation mechanisms.
- Authors: Laine E, Chauvot de Beauchêne I, Perahia D, Auclair C, Tchertanov L
- Issue date: 2011 Jun
- Chemotherapeutic drug selectivity between wild-type and mutant BRaf kinases in colon cancer.
- Authors: Zhang J, Ji T
- Issue date: 2017 Jan
- Function of activation loop tyrosine phosphorylation in the mechanism of c-Kit auto-activation and its implication in sunitinib resistance.
- Authors: DiNitto JP, Deshmukh GD, Zhang Y, Jacques SL, Coli R, Worrall JW, Diehl W, English JM, Wu JC
- Issue date: 2010 Apr
- Molecular basis of the constitutive activity and STI571 resistance of Asp816Val mutant KIT receptor tyrosine kinase.
- Authors: Foster R, Griffith R, Ferrao P, Ashman L
- Issue date: 2004 Oct