Comparative Analysis of mRNA Isoform Expression in Cardiac Hypertrophy and Development Reveals Multiple Post-Transcriptional Regulatory Modules (original) (raw)
Figure 1
Gene expression profiling in cardiac hypertrophy and development.
(A) Schematic of datasets used in our analysis. Top, hypertrophy data with TAC period indicated (W = week). All hypertrophy samples were derived from the left ventricle and thus were named LVH. They were compared with Sham samples. Bottom, development samples. E, embryonic day (for mouse samples); P, postnatal day (for rat samples). ED1 is comparison of E10.5 + E11.5 with E13.5 + E14.5 and ED2 is comparison of E13.5 + E14.5 with E16.5 + E18.5. PD1 is comparison of P1 with P20 and PD2 is comparison of P20 with P49. EA is comparison of E17 with adult. E10.5, E11.5, and EA were based on the whole heart, and others were based on the left ventricle. All ratios were derived from expression level at a later development time point divided by that at an earlier point. (B) Clustering of genes and samples using gene expression changes. Expression changes are standardized log2(ratio) or z, which are shown in a heatmap using the color scale shown at the bottom. A total of 1,945 genes with z >2 in at least one of the samples are shown. Hierarchical clustering is based on Pearson correlation and the average linkage method. (C) Venn diagram of genes regulated in development (DEV) and hypertrophy (LVH). Genes were selected from five development datasets, i.e. ED1, ED2, PD1, PD2, and EA, and three 1 W TAC sets, i.e. LVH1, LVH2, and LVH3. A gene was selected if its z is greater than 2 in at least one sample and the direction of its regulation is consistent across samples. Fisher's exact test was used to assess the significance of bias in genes overlapped between DEV and LVH. (D) Significant Biological Process (BP, top) and Cellular Component (CC, bottom) terms regulated in hypertrophy. Only top 10 terms are shown for BP and CC. The average p-value of three 1 W TAC samples was used to sort entries. P-values in other samples are also shown for comparison. To remove redundancy, we eliminated GO terms that overlapped by more than 50% of associated genes with another term that had a more significant p-value. P-values are presented in a heatmap according to the color scheme shown in the graph.