Computational modeling and experimental analysis for the diagnosis of cell survival/death for Akt protein

Abstract

Abstract Background Signalling systems that control cell decisions allow cells to process input signals by apprehending the information of the cell to give one of these two feasible outputs: cell death or cell survival. In this paper, a well-structured control design methodology supported by a hierarchical design system was developed to examine signalling networks that control cell decisions by considering a combinations of three primary signals (input proteins): the pro survival growth factors, epidermal growth factor (EGF), insulin, and the pro death cytokine, tumour necrosis factor-α (TNF), for AKT/protein kinase B. The AKT actions were examined by using the three input proteins for cell survival/apoptosis for a period of 0–24 h in 13 different slices for ten different combinations. Results Experimental analysis was performed to consider the reactions that were essential to explain the action of AKT. Furthermore, pre-processing and data normalization were performed by using standard deviation, plotting histograms, and scatter plots. Feature extraction and selection were performed using correlation matrix. Radial basis function (RBF) and multiple-layer perceptron (MLP) were used for cell survival/death classification. For all the ten combinations of the three input proteins, 42.85, 347.22, 153.13 were obtained as the minimum value, maximum value, and mean value, respectively, and 126.11 was obtained as the standard deviation for 5-0-5 ng/ml combinations of TNF-EGF-Insulin. The results obtained with MLP 10-8-1 were found to outperform other techniques. Conclusion The results from the experimental analysis indicate that it is possible to build self-consistent compendia cell-signalling data based on AKT protein which were simulated computationally to yield important insights for the control of cell survival/death.