RNAseq analysis of heart tissue from mice treated with atenolol and isoproterenol reveals a reciprocal transcriptional response

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dc.contributor.authorBergmann, Sven
dc.date.accessioned2021-10-08T06:20:22Z
dc.date.available2021-10-08T06:20:22Z
dc.date.issued2016
dc.description.abstractAbstract Background The transcriptional response to many widely used drugs and its modulation by genetic variability is poorly understood. Here we present an analysis of RNAseq profiles from heart tissue of 18 inbred mouse strains treated with the β-blocker atenolol (ATE) and the β-agonist isoproterenol (ISO). Results Differential expression analyses revealed a large set of genes responding to ISO (n = 1770 at FDR = 0.0001) and a comparatively small one responding to ATE (n = 23 at FDR = 0.0001). At a less stringent definition of differential expression, the transcriptional responses to these two antagonistic drugs are reciprocal for many genes, with an overall anti-correlation of r = −0.3. This trend is also observed at the level of most individual strains even though the power to detect differential expression is significantly reduced. The inversely expressed gene sets are enriched with genes annotated for heart-related functions. Modular analysis revealed gene sets that exhibit coherent transcription profiles across some strains and/or treatments. Correlations between these modules and a broad spectrum of cardiovascular traits are stronger than expected by chance. This provides evidence for the overall importance of transcriptional regulation for these organismal responses and explicits links between co-expressed genes and the traits they are associated with. Gene set enrichment analysis of differentially expressed groups of genes pointed to pathways related to heart development and functionality. Conclusions Our study provides new insights into the transcriptional response of the heart to perturbations of the β-adrenergic system, implicating several new genes that had not been associated to this system previously.
dc.identifier.apacitationBergmann, S. (2016). RNAseq analysis of heart tissue from mice treated with atenolol and isoproterenol reveals a reciprocal transcriptional response. <i>BMC Genomics</i>, 17(1), 174 - 177. http://hdl.handle.net/11427/34262en_ZA
dc.identifier.chicagocitationBergmann, Sven "RNAseq analysis of heart tissue from mice treated with atenolol and isoproterenol reveals a reciprocal transcriptional response." <i>BMC Genomics</i> 17, 1. (2016): 174 - 177. http://hdl.handle.net/11427/34262en_ZA
dc.identifier.citationBergmann, S. 2016. RNAseq analysis of heart tissue from mice treated with atenolol and isoproterenol reveals a reciprocal transcriptional response. <i>BMC Genomics.</i> 17(1):174 - 177. http://hdl.handle.net/11427/34262en_ZA
dc.identifier.issn1471-2164
dc.identifier.ris TY - Journal Article AU - Bergmann, Sven AB - Abstract Background The transcriptional response to many widely used drugs and its modulation by genetic variability is poorly understood. Here we present an analysis of RNAseq profiles from heart tissue of 18 inbred mouse strains treated with the β-blocker atenolol (ATE) and the β-agonist isoproterenol (ISO). Results Differential expression analyses revealed a large set of genes responding to ISO (n = 1770 at FDR = 0.0001) and a comparatively small one responding to ATE (n = 23 at FDR = 0.0001). At a less stringent definition of differential expression, the transcriptional responses to these two antagonistic drugs are reciprocal for many genes, with an overall anti-correlation of r = −0.3. This trend is also observed at the level of most individual strains even though the power to detect differential expression is significantly reduced. The inversely expressed gene sets are enriched with genes annotated for heart-related functions. Modular analysis revealed gene sets that exhibit coherent transcription profiles across some strains and/or treatments. Correlations between these modules and a broad spectrum of cardiovascular traits are stronger than expected by chance. This provides evidence for the overall importance of transcriptional regulation for these organismal responses and explicits links between co-expressed genes and the traits they are associated with. Gene set enrichment analysis of differentially expressed groups of genes pointed to pathways related to heart development and functionality. Conclusions Our study provides new insights into the transcriptional response of the heart to perturbations of the β-adrenergic system, implicating several new genes that had not been associated to this system previously. DA - 2016 DB - OpenUCT DP - University of Cape Town IS - 1 J1 - BMC Genomics LK - https://open.uct.ac.za PY - 2016 SM - 1471-2164 T1 - RNAseq analysis of heart tissue from mice treated with atenolol and isoproterenol reveals a reciprocal transcriptional response TI - RNAseq analysis of heart tissue from mice treated with atenolol and isoproterenol reveals a reciprocal transcriptional response UR - http://hdl.handle.net/11427/34262 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/34262
dc.identifier.vancouvercitationBergmann S. RNAseq analysis of heart tissue from mice treated with atenolol and isoproterenol reveals a reciprocal transcriptional response. BMC Genomics. 2016;17(1):174 - 177. http://hdl.handle.net/11427/34262.en_ZA
dc.language.isoeng
dc.publisher.departmentDepartment of Integrative Biomedical Sciences (IBMS)
dc.publisher.facultyFaculty of Health Sciences
dc.sourceBMC Genomics
dc.source.journalissue1
dc.source.journalvolume17
dc.source.pagination174 - 177
dc.source.urihttps://dx.doi.org/10.1186/s12864-016-3059-6
dc.subject.otherAtenolol
dc.subject.otherCardiac hypertrophy
dc.subject.otherIsoproterenol
dc.subject.otherMouse heart
dc.subject.otherRNAseq
dc.subject.otherβ-adrenergic system
dc.subject.otherAnimals
dc.subject.otherAtenolol
dc.subject.otherComputational Biology
dc.subject.otherGene Expression Profiling
dc.subject.otherGene Expression Regulation
dc.subject.otherGene Ontology
dc.subject.otherGene Regulatory Networks
dc.subject.otherHeart
dc.subject.otherIsoproterenol
dc.subject.otherMice
dc.subject.otherMice, Inbred Strains
dc.subject.otherSequence Analysis, RNA
dc.subject.otherSoftware
dc.titleRNAseq analysis of heart tissue from mice treated with atenolol and isoproterenol reveals a reciprocal transcriptional response
dc.typeJournal Article
uct.type.publicationResearch
uct.type.resourceJournal Article
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