A Multi-Network Comparative Analysis of Transcriptome and Translatome Identifies Novel Hub Genes in Cardiac Remodeling

Etienne Boileau, Shirin Doroudgar, Eva Riechert, Lonny Jürgensen, Thanh Cao Ho, Hugo A. Katus, Mirko Völkers, Christoph Dieterich

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Our understanding of the transition from physiological to pathological cardiac hypertrophy remains elusive and largely based on reductionist hypotheses. Here, we profiled the translatomes of 15 mouse hearts to provide a molecular blueprint of altered gene networks in early cardiac remodeling. Using co-expression analysis, we showed how sub-networks are orchestrated into functional modules associated with pathological phenotypes. We discovered unappreciated hub genes, many undocumented for their role in cardiac hypertrophy, and genes in the transcriptional network that were rewired in the translational network, and associated with semantically different subsets of enriched functional terms, such as Fam210a, a novel musculoskeletal modulator, or Psmd12, implicated in protein quality control. Using their correlation structure, we found that transcriptome networks are only partially reproducible at the translatome level, providing further evidence of post-transcriptional control at the level of translation. Our results provide novel insights into the complexity of the organization of in vivo cardiac regulatory networks.

Original languageEnglish (US)
Article number583124
JournalFrontiers in Genetics
Volume11
DOIs
StatePublished - Nov 16 2020
Externally publishedYes

Keywords

  • cardiac hypertrophy
  • cardiovascular
  • co-expression networks
  • transcription/RNA-seq
  • translation/Ribo-seq

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Genetics(clinical)

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