A Multi-Network Comparative Analysis of Transcriptome and Translatome Identifies Novel Hub Genes in Cardiac Remodeling
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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-11-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2020.583124/full |
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| author | Etienne Boileau Etienne Boileau Etienne Boileau Shirin Doroudgar Shirin Doroudgar Eva Riechert Eva Riechert Lonny Jürgensen Lonny Jürgensen Thanh Cao Ho Hugo A. Katus Hugo A. Katus Mirko Völkers Mirko Völkers Christoph Dieterich Christoph Dieterich Christoph Dieterich |
| author_facet | Etienne Boileau Etienne Boileau Etienne Boileau Shirin Doroudgar Shirin Doroudgar Eva Riechert Eva Riechert Lonny Jürgensen Lonny Jürgensen Thanh Cao Ho Hugo A. Katus Hugo A. Katus Mirko Völkers Mirko Völkers Christoph Dieterich Christoph Dieterich Christoph Dieterich |
| author_sort | Etienne Boileau |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T15:31:04Z |
| format | Article |
| id | doaj.art-1a54f472e8994a88ac56e09d6cb0906a |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-21T15:31:04Z |
| publishDate | 2020-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-1a54f472e8994a88ac56e09d6cb0906a2022-12-21T18:58:46ZengFrontiers Media S.A.Frontiers in Genetics1664-80212020-11-011110.3389/fgene.2020.583124583124A Multi-Network Comparative Analysis of Transcriptome and Translatome Identifies Novel Hub Genes in Cardiac RemodelingEtienne Boileau0Etienne Boileau1Etienne Boileau2Shirin Doroudgar3Shirin Doroudgar4Eva Riechert5Eva Riechert6Lonny Jürgensen7Lonny Jürgensen8Thanh Cao Ho9Hugo A. Katus10Hugo A. Katus11Mirko Völkers12Mirko Völkers13Christoph Dieterich14Christoph Dieterich15Christoph Dieterich16Section of Bioinformatics and Systems Cardiology, Klaus Tschira Institute for Integrative Computational Cardiology, Heidelberg, GermanyDepartment of Internal Medicine III (Cardiology, Angiology, and Pneumology), University Hospital Heidelberg, Heidelberg, GermanyDZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Berlin, GermanyDepartment of Internal Medicine III (Cardiology, Angiology, and Pneumology), University Hospital Heidelberg, Heidelberg, GermanyDZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Berlin, GermanyDepartment of Internal Medicine III (Cardiology, Angiology, and Pneumology), University Hospital Heidelberg, Heidelberg, GermanyDZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Berlin, GermanyDepartment of Internal Medicine III (Cardiology, Angiology, and Pneumology), University Hospital Heidelberg, Heidelberg, GermanyDZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Berlin, GermanyDepartment of Internal Medicine III (Cardiology, Angiology, and Pneumology), University Hospital Heidelberg, Heidelberg, GermanyDepartment of Internal Medicine III (Cardiology, Angiology, and Pneumology), University Hospital Heidelberg, Heidelberg, GermanyDZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Berlin, GermanyDepartment of Internal Medicine III (Cardiology, Angiology, and Pneumology), University Hospital Heidelberg, Heidelberg, GermanyDZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Berlin, GermanySection of Bioinformatics and Systems Cardiology, Klaus Tschira Institute for Integrative Computational Cardiology, Heidelberg, GermanyDepartment of Internal Medicine III (Cardiology, Angiology, and Pneumology), University Hospital Heidelberg, Heidelberg, GermanyDZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Berlin, GermanyOur 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.https://www.frontiersin.org/articles/10.3389/fgene.2020.583124/fullcardiovascularcardiac hypertrophytranscription/RNA-seqtranslation/Ribo-seqco-expression networks |
| spellingShingle | Etienne Boileau Etienne Boileau Etienne Boileau Shirin Doroudgar Shirin Doroudgar Eva Riechert Eva Riechert Lonny Jürgensen Lonny Jürgensen Thanh Cao Ho Hugo A. Katus Hugo A. Katus Mirko Völkers Mirko Völkers Christoph Dieterich Christoph Dieterich Christoph Dieterich A Multi-Network Comparative Analysis of Transcriptome and Translatome Identifies Novel Hub Genes in Cardiac Remodeling Frontiers in Genetics cardiovascular cardiac hypertrophy transcription/RNA-seq translation/Ribo-seq co-expression networks |
| title | A Multi-Network Comparative Analysis of Transcriptome and Translatome Identifies Novel Hub Genes in Cardiac Remodeling |
| title_full | A Multi-Network Comparative Analysis of Transcriptome and Translatome Identifies Novel Hub Genes in Cardiac Remodeling |
| title_fullStr | A Multi-Network Comparative Analysis of Transcriptome and Translatome Identifies Novel Hub Genes in Cardiac Remodeling |
| title_full_unstemmed | A Multi-Network Comparative Analysis of Transcriptome and Translatome Identifies Novel Hub Genes in Cardiac Remodeling |
| title_short | A Multi-Network Comparative Analysis of Transcriptome and Translatome Identifies Novel Hub Genes in Cardiac Remodeling |
| title_sort | multi network comparative analysis of transcriptome and translatome identifies novel hub genes in cardiac remodeling |
| topic | cardiovascular cardiac hypertrophy transcription/RNA-seq translation/Ribo-seq co-expression networks |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2020.583124/full |
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