Biological process analysis:
To identify the most affected biological process three types of ontology
analysis was done in this study. First, Gene Set Enrichment Analysis
(GSEA) tool was used to highlight overrepresented genes and enriched
pathways (Mootha et al., 2003; Subramanian et al., 2005). GSEAPreranked
analysis tool was recruited for which we used the list of differentially
expressed genes which had been ordered based on their fold changes. We
used biological process gene ontology and decreased minimum set size
from 15 to 1 (Mootha et al., 2003; Subramanian et al., 2005). Second, we
used Enrichr webtool to dissect data in more detail. In this case, the
most affected biological processes were filtered and sorted based on
their adjusted p-value and number of differentially expressed
genes (Chen et al., 2013; Kuleshov et al., 2016). Third, we did
biological processes ontology on the constructed gene regulatory network
in Cytoscape software using ClueGO and CluePedia plugins. In the ClueGO
and CluePedia plugins advanced statistical option of the tools,
two-sided hypergeometric test was selected to calculate the importance
of each term and Bonferroni step-down was used for p-valuecorrection (Bindea, Galon, & Mlecnik, 2013; Bindea et al., 2009). The
terms with p-value < 0.05 were considered as meaningful
terms.