TY - JOUR
T1 - A Multi-Network Comparative Analysis of Transcriptome and Translatome Identifies Novel Hub Genes in Cardiac Remodeling
AU - Boileau, Etienne
AU - Doroudgar, Shirin
AU - Riechert, Eva
AU - Jürgensen, Lonny
AU - Ho, Thanh Cao
AU - Katus, Hugo A.
AU - Völkers, Mirko
AU - Dieterich, Christoph
N1 - Funding Information:
EB and CD acknowledge support by the Klaus Tschira Stiftung gGmbH [00.219.2013]. CD, SD, and MV acknowledge the DZHK (German Centre for Cardiovascular Research) Partner Site Heidelberg/Mannhein. MV was supported by the Deutsche Forschungsgemeinschaft, Plus 3 Programme of the Boehringer Ingelheim Foundation (BISI) and Baden Württemberg Stiftung. SD is supported by the DZHK (German Centre for Cardiovascular Research) Excellence Program.
Publisher Copyright:
© Copyright © 2020 Boileau, Doroudgar, Riechert, Jürgensen, Ho, Katus, Völkers and Dieterich.
PY - 2020/11/16
Y1 - 2020/11/16
N2 - 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.
AB - 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.
KW - cardiac hypertrophy
KW - cardiovascular
KW - co-expression networks
KW - transcription/RNA-seq
KW - translation/Ribo-seq
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U2 - 10.3389/fgene.2020.583124
DO - 10.3389/fgene.2020.583124
M3 - Article
AN - SCOPUS:85096927849
SN - 1664-8021
VL - 11
JO - Frontiers in Genetics
JF - Frontiers in Genetics
M1 - 583124
ER -