Integrative Bioinformatic Analyses of Global Transcriptome Data Decipher Novel Molecular Insights into Cardiac Anti-Fibrotic Therapies

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Abstract
Integrative 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.
Funding Information
  • Bundesministerium Bildung (Era-Net grant 01KT1801, MIRACUM Consortium grant 01ZZ1801A, Foundation Leducq, ERA Network grant EXPERT)
  • Deutsche Forschungsgemeinschaft (KFO FOR311-2, TH903/20-1)
  • BHF Centre for Regenerative Medicine at Imperial College London (RM/17/1/33377)
  • Molecular Medicine program of the Hannover Biomedical Research School (HBRS) (PhD fellowship)

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