In silico analysis
To explore the pathways in which the genes are involved with, we used Reactome Pathway Database (https://reactome.org/ - Version 72 Released). A binomial test is used to calculate the probability for each result and the p-values are corrected for the multiple testing (Benjamini–Hochberg procedure) that arises from evaluating the submitted list of identifiers against every pathway 24,25. We considered significant, those p-values <0.05. Data were crossed with other resources such as NCBI, Ensembl, UniProt, KEGG (Gene and Compound), ChEBI, PubMed and GO.
Pairwise gene expression correlation was calculated using Pearson’s method and the data was displayed using the heatmap.2 function (packages: STRINGR, GGPLOT2, GRID, gridExtra, and GGBIPLOT) with the same setting as the UPGMA previously described.