Functional analysis and interpretation

Area-proportional Venn diagrams and analysis of differentially expressed gene lists were performed using BioVenn [26]. Functional enrichment analysis of differentially expressed genes and visualization of functional networks was performed using Cytoscape/ClueGo version 2.5.7 [27]. Only genes with p<0.05 were included into the analysis. Functional enrichment analysis was conducted using a two-sided hypergeometric test with Bonferroni step down correction. Latest “GO Bological Process”, “GO Immune System Process” and KEGG databases were used. GO levels were set in the interval from 3 to 8, minimum of genes per GO term or KEGG pathway threshold was 2 genes and 4%. The Kappa score threshold of 0.4 was set to determine term-term interactions and visualization of term connections as a network. ClueGo 2.5.7 was also used for visualization of networks, comparative analysis and sorting of whole transcriptome enrichment results using predefined terms from topGO and KEGGREST analyses. Only terms and pathways with p<0.05 were included to the input data.