Figure 4

Genes associated with lung function decline. mRNAs of importance to fibrosis were identified by correlating their longitudinal gene expression changes to the decline in lung function observed in the respective model. (a) The top 50 highest expressed mRNAs showing strong anti-correlation to lung compliance (Pearson r ≤ − 0.85) and significant alteration (adj. p-value ≤ 0.05 at day 21 in both models) with consistent direction of expression (mean log₂FC ≥ 0 in both models) are shown. log₂ fold changes on day 21 are depicted together with the gene expression profile over all five time points. A list of all lung function (anti-) correlated transcripts, including correlation coefficients is supplied as Suppl. Table 2. (b) Venn diagrams of mRNAs showing strong lung function (anti-)correlation (threshold defined as |Pearson r|≥ 0.85) in either only one (blue = Bleomycin, red = AAV-TGFβ1) or both models. EnrichR analysis of Reactome, KEGG and GO biological pathways as well as ARCHS4 transcription factor co-expression, kinase co-expression and tissue predictions for all commonly lung-function anti-correlated genes. (c) Top 10 lung function-correlated (i.e. downregulated) mRNAs identified using the criteria from (a), adapted for positive correlation.