A personalized, multiomics approach identifies genes involved in cardiac hypertrophy and heart failure

Two types of responses to stressor-induced heart failure. a Histograms of the pre-ISO (blue) and post-ISO (red) heart masses of the HMDP strains. b Typical Differentially Expressed Genes (DEGs) show clear population-average fold-change allowing distinguishing the two populations of strains. c An example of such strong DEG, namely Serpina3n. d Histogram of the heart mass fold-change (FC) computed for each strain from the HMDP. e Expression FC at the individual level can lead to cases were the population-average FC is null while the individual FCs are not. f Kcnip2 is a good example of a gene with no population-wide average FC. g However, at the individual level, Kcnip2 shows strong variations, as seen in the histogram of individual FCs at the strain level (log2 of post over pre-ISO expression ratio). In particular, some strains have a 4-fold decrease of expression (？2 in log2), while others have a 4-fold increase (+2). h For better visualization, the strain-specific heart mass FC is shown by decreasing strength. Red bars indicate increase and blue bars decrease in value. i Serpina3n log FC is shown with the same strain ordering than in (h). Its population-wide FC is high (3.9), with most strains showing a strong positive FC (red bars). j However, the correlation of Serpina3n FC with the heart mass FC is not significant (r？=？？0.09, p？=？0.43). k On the other hand, Kcnip2 shows a weak population-wide FC (FC？=？0.85). In particular, some strains show an increased expression (red bars) while others show a decreased expression (blue bars). The red arrow indicates the 129？×？1/SvJ strain in which Kcnip2 has previously been shown to be down-regulated during cardiac hypertrophy.24 l Contrary to Serpina3n, Kcnip2 FC is significantly correlated to heart mass FC (r？=？0.4, p？=？1.5e-4), with increased expression corresponding to high hypertrophy and decreased expression corresponding to low hypertroph