In heart failure reactivation of RNA-binding protein function results in expression of thousands of fetal-specific isoforms

Table S3: Differential gene expression analysis Shown is the differential expression analysis between: iPSC-derived cardiovascular progenitor cells (iPSC-CVPC) and adult heart; iPSC-CVPC and adult arteria; adult heart and adult arteria. For each gene, we report: gene ID; gene name; the tested tissues (tissue 1 and tissue 2); effect size, standard error, p-value and FDR correction (Bonferroni). Effect size &gt; 0 corresponds to genes where the expression in tissue 1 is greater than tissue 2.<br>Table S4: Functional enrichment analysis (genes) The table shows the functional enrichment analysis for genes differentially expressed between each pair of CVS tissues (Table S3). For each gene set, we report: the tested tissues (tissue 1 and tissue 2); the gene set collection, as defined by MSigDB, the gene set name and its URL; the number of tested genes in the gene set; the average effect size for all the tested genes in the gene set and for all the other expressed genes; p-value (t-test); and FDR (Benjamini-Hochberg).<br>Table S5: Differential isoform expression analysis Shown is the differential isoform expression analysis between: iPSC-CVPC and adult heart; iPSC-CVPC and adult arteria; adult heart and adult arteria. For each isoform, we report: isoform ID, gene ID, gene name; the tested tissues (tissue 1 and tissue 2); effect size, standard error, p-value and FDR correction (Bonferroni); mean isoform use in each of the two tested tissues and the log₂ ratio between them; whether the isoform is differentially expressed (FDR &lt; 0.05). Effect size &gt; 0 corresponds to isoforms where the expression in tissue 1 is greater than tissue 2.<br>Table S6: Functional enrichment analysis (isoforms) The table shows the functional enrichment analysis of genes that have at least one CVS tissue-specific isoform, compared with genes that do not have differentially expressed isoforms between each pair of CVS tissues (Table S5). For each gene set, we report: the tested tissues (tissue 1 and tissue 2); the gene set collection, as defined by MSigDB, the gene set name and its URL; the number of tested genes in the gene set; the enrichment calculated using the <i>estimate</i> parameter in the <i>fisher.test</i> function in R; p-value (Fisher’s exact test); and FDR (Benjamini-Hochberg).<br>Table S13: Differential gene expression analysis (cell types) Shown are the associations between the expression of each expressed gene and isoform and cell type proportions in all bulk RNA-seq CVS samples. For each gene and isoform, we report: isoform ID, gene ID, gene name; the cell type whose proportion is tested for association with expression; effect size, standard error, p-value, FDR correction (Bonferroni); whether the expression of the gene or isoform is associated with cell type proportion (FDR &lt; 0.05 and effect size &gt; 0).<br>Table S14: Functional enrichment analysis (cell types) The table shows the functional enrichment analysis for genes associated with each cell type. The table is organized as Table S4, with a difference: cell type, rather than “tissue 1” and “tissue 2” is reported. For each cell type, we determined the association (effect size) between its proportion and the expression of each gene, and used the effect sizes of all expressed genes as input for gene set enrichment analysis (GSEA). We observed that the most significantly enriched gene sets corresponded to the main function associated with each cell type, including mitochondrial and cell respiration functions for cardiac muscle, immune response for immune cells, cytoskeleton and actin binding for smooth muscle.<br>Table S15: Differential gene and isoform expression using cell type proportions as covariates Shown is the differential expression analysis for both genes and isoforms performed using ridge regression and cell type proportions as covariates between: iPSC-CVPC and adult heart; iPSC-CVPC and adult arteria; adult heart and adult arteria. For each gene and isoform, we report: isoform ID, gene ID and gene name; the tested tissues (tissue 1 and tissue 2); the covariate, including “tissue”, which represents the differential expression between tissue 1 and tissue 2, and each of the cell types; effect size, standard error, p-value and FDR correction (Bonferroni).<br>Table S18: Differential expression between heart failure and healthy CVS tissues The table shows the results from differential expression analysis of genes and isoforms between pre-LVAD samples and the three healthy CVS tissues (iPSC-CVPC, adult heart and adult arteria). Columns A-D show gene and transcript information, including: transcript ID, gene ID, gene name, and analysis type (gene or isoform). Columns E-F show the pairs of tested tissues. Columns G-J show the effect size, its standard error, p-value and FDR correction (Bonferroni’s method). FDR correction was performed independently on genes and isoforms.