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Glucocorticoid activity regulates glucocorticoid receptor isoform expression and downstream gene transcription in humans

The University of Queensland
Associate Professor Warrick Inder (Author) Dr Adam Ewing (Author) Dr Jack Lockett (Author) Dr Sahar Keshvari (Author) Honorary Professor Vicki Clifton (Author)
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ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Adc&rfr_id=info%3Asid%2FANDS&rft_id=info:doi10.48610/ee0c38e&rft.title=Glucocorticoid activity regulates glucocorticoid receptor isoform expression and downstream gene transcription in humans&rft.identifier=10.48610/ee0c38e&rft.publisher=The University of Queensland&rft.description=Supplementary materials for manuscript to be published:- Complete list of R/Python packages used in analysis- Table S1 - Pearson correlations between isoform expression at 0800 h. C = cytoplasmic, N = nuclear. p < 0.05*; p < 0.01**; p < 0.001***; p < 0.0001 ****.- Table S2 - Pearson correlations between isoform expression at 1200 h. C = cytoplasmic, N = nuclear. p < 0.05*; p < 0.01**; p < 0.001***; p < 0.0001 ****.- Table S3 - RNA-Seq gene expression correlations with nuclear GR isoform expression at 0800 h (Spearman's, FDR q < 0.05)Table S4 - RNA-Seq gene expression correlations with cytoplasmic GR isoform expression at 0800 h (Spearman's, FDR q < 0.05)- Figure S1 - Differences in GR isoform expression between groups at 1200 h for cytoplasmic (A) and nuclear (B) locations, assessed using linear regression with adjustment for age, menopausal status and BMI, post-hoc comparisons using Tukey's test. p < 0.05*, p < 0.01**, p < 0.001 ***, p < 0.0001****.- Figure S2 - Principle components analysis of isoform expression at 0800h across groups, 89.6% of variance in data explained by PC1 and PC2 - participants cluster together based isoform expression. Note: GRP expression and participants not expressing all other isoforms excluded from analysis as PCA requires a complete dataset.- Figure S3 - Spearman correlations between RNASeq read count and nuclear GR isoform expression displayed in a Venn diagram. Each oval represents the isoform labelled and intersections represent correlations shared by the isoforms included. Counts represent the number (%) of genes correlated with each isoform/combination of isoforms (total = 78).Figure S4 - Spearman correlations between RNASeq read count and cytoplasmic GR isoform expression. UpSet plot showing the number of genes correlated with each isoform (left histogram, Set Size), the combinations of isoforms (grey dots), and the number of genes correlated with that combination (upper histogram, Interaction Size).- Figure S5 - Pathway enrichment analysis of genes correlated with at least one GR isoform (cytoplasmic or nuclear, n = 218; FDR q < 0.05). Nodes represent gene pathways (Gene Ontology: Biological Process or Reactome Pathway) with size based on total number of genes in pathway, edges represent overlap between pathways with size based on number of genes overlap. Full list of genes included in analysis available in supplementary data (Table S3 and S4).- Figure S6 - Pathway enrichment analysis of genes differentially expressed in other groups compared with AI (n = 91; FDR q < 0.05). Nodes represent gene pathways (Gene Ontology: Biological Process or Reactome Pathway) with size and colour intensity based on total number of genes in pathway, edges represent overlap between pathways with size based on number of genes overlap.- Supplementary References list&rft.creator=Associate Professor Warrick Inder&rft.creator=Dr Adam Ewing&rft.creator=Dr Jack Lockett&rft.creator=Dr Sahar Keshvari&rft.creator=Honorary Professor Vicki Clifton&rft.creator=Ms Zarqa Saif&rft.date=2022&rft_subject=glucocorticoid receptor&rft_subject=glucocorticoids&rft_subject=Cushing's syndrome&rft_subject=adrenal insufficiency&rft.type=dataset&rft.language=English Access the data

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j.lockett@uq.edu.au

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Supplementary materials for manuscript to be published:- Complete list of R/Python packages used in analysis- Table S1 - Pearson correlations between isoform expression at 0800 h. C = cytoplasmic, N = nuclear. p < 0.05*; p < 0.01**; p < 0.001***; p < 0.0001 ****.- Table S2 - Pearson correlations between isoform expression at 1200 h. C = cytoplasmic, N = nuclear. p < 0.05*; p < 0.01**; p < 0.001***; p < 0.0001 ****.- Table S3 - RNA-Seq gene expression correlations with nuclear GR isoform expression at 0800 h (Spearman's, FDR q < 0.05)Table S4 - RNA-Seq gene expression correlations with cytoplasmic GR isoform expression at 0800 h (Spearman's, FDR q < 0.05)- Figure S1 - Differences in GR isoform expression between groups at 1200 h for cytoplasmic (A) and nuclear (B) locations, assessed using linear regression with adjustment for age, menopausal status and BMI, post-hoc comparisons using Tukey's test. p < 0.05*, p < 0.01**, p < 0.001 ***, p < 0.0001****.- Figure S2 - Principle components analysis of isoform expression at 0800h across groups, 89.6% of variance in data explained by PC1 and PC2 - participants cluster together based isoform expression. Note: GRP expression and participants not expressing all other isoforms excluded from analysis as PCA requires a complete dataset.- Figure S3 - Spearman correlations between RNASeq read count and nuclear GR isoform expression displayed in a Venn diagram. Each oval represents the isoform labelled and intersections represent correlations shared by the isoforms included. Counts represent the number (%) of genes correlated with each isoform/combination of isoforms (total = 78).Figure S4 - Spearman correlations between RNASeq read count and cytoplasmic GR isoform expression. UpSet plot showing the number of genes correlated with each isoform (left histogram, Set Size), the combinations of isoforms (grey dots), and the number of genes correlated with that combination (upper histogram, Interaction Size).- Figure S5 - Pathway enrichment analysis of genes correlated with at least one GR isoform (cytoplasmic or nuclear, n = 218; FDR q < 0.05). Nodes represent gene pathways (Gene Ontology: Biological Process or Reactome Pathway) with size based on total number of genes in pathway, edges represent overlap between pathways with size based on number of genes overlap. Full list of genes included in analysis available in supplementary data (Table S3 and S4).- Figure S6 - Pathway enrichment analysis of genes differentially expressed in other groups compared with AI (n = 91; FDR q < 0.05). Nodes represent gene pathways (Gene Ontology: Biological Process or Reactome Pathway) with size and colour intensity based on total number of genes in pathway, edges represent overlap between pathways with size based on number of genes overlap.- Supplementary References list

Issued: 24 02 2022

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