Abstract
The present study investigated the rate of change (mutation) in TP53 and the associated functional partner genes and revealed that they play very significant role in hepatocellular carcinoma and liver cancer disease conditions in humans. Genetic correlation analysis has shown that there is very high association, strong relationship with significant impact between TP53 and the functional partner genes. The strength of association between TP53 gene and other functional partners gene was found to be high (> 0.5) in normal liver but low than in cancerous liver. The proteomic parameters of TP53 and other functional partner genes such as the molecular weights, number of amino acids, theoretical pl, total number of atoms, total number of positive and negative amino acids residues, extinction coefficients, estimated half-life, instability index, aliphatic index and hydropathicity were revealed in the study and viewed using the circos visualizer which showed bigger strands for genes with high molecular weights. The expasy.org prosites analysis of the TP53 and associated functional partner genes revealed the functional domain protein site reaction hotspots with the corresponding amino acids. The main prosites reaction hotspots were the protein kinase II phosphorylation site (PKC) which was similar for all the associated genes. Other domain reaction hotspots for TP53 and associated genes includes N-glycosylation sites, N-myristylation sites, N-Amidation sites, Tyrosine II kinase phosphorylation sites I and II, the casein II protein kinase phosphorylation sites (CK2) and the cAMP and cGMP phosphorylation sites. Two principal components were used to explain the variations in dimensionality of the TP53 and associated genes. ATM gene showed the highest loading value in PC1 while EP300 gene exerts the highest impact in terms of dimensionality in PC2. The principal component axes delineated the genes into two major cluster sets. Major cluster one had four genes which major two had 6 genes. The intensity of interactions among the genes to induce hepatocellular carcinoma and liver cancer was demonstrated using interactive heatmap with red colour depicting intense interactions, black colour depicting moderate interactions and green colour depicting slow interactions.