Article information
2020 , Volume 25, ¹ 6, p.4-49
Senotrusova S.D., Voropaeva O.F., Shokin Y.I.
Application of minimal mathematical models for the dynamics of the signaling pathway of the p53 - miRNA to the analysis of laboratory data
This study addresses the practical use of minimal mathematical models of the dynamics of a hypothetical system of the p53 signaling pathway to describe a fairly wide range of laboratory experiments. In such system, the interaction of p53 and p53 inhibitor proteins is mediated by microRNAs that form a positive feedback loop with p53. A basic model, new minimal models developed on its basis, an algorithm for the numerical solution of direct and inverse coefficient problems, and the results of comparing the obtained numerical solutions with experimental data on the dynamics of the levels of p53, p21, Bax proteins, inhibitor proteins Mdm2, Wip1, Sirt1, and various microRNAs (miR-16, miR-34a, miR-192, miR-194, miR-215) under stress conditions are presented. In numerical experiments, the main mechanisms of the p53 signaling pathway were investigated. A synergistic effect of hyperactivation of the p53 signaling pathway and bimodal switching mechanisms has been demonstrated. We show the key role of p53-dependent microRNAs in the implementation of some hypothetical therapeutic strategies associated with the control mechanism for activation of cells apoptosis. Within the framework of the accepted basic model, we estimated the probability of mismatch in the diagnosis of the patient’s status. The status is based on the analysis of the level of p53-dependent microRNAs and p53, with weak and moderate deregulation of microRNAs.
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Keywords: mathematical model, numerical analysis, inverse coefficient problem, p53, positive feedback, p21, Bax, Mdm2, Wip1, Sirt1, miR-16, miR-34a, miR-192, miR-194, miR-215, synergy, bimodal switch, deregulation of microRNA
doi: 10.25743/ICT.2020.25.6.002
Author(s): Senotrusova Sofya Dmitrievna Position: Junior Research Scientist Office: Federal Research Center for Information and Computational Technologies Address: 630090, Russia, Novosibirsk, Academician M.A. Lavrentiev avenue, 6
E-mail: senotrusova.s@mail.ru SPIN-code: 2066-6054Voropaeva Olga Falaleevna Dr. Position: Leading research officer Office: Federal Research Centerfor Information and Computational Technologies Address: 630090, Russia, Novosibirsk, ac. Lavrentyev Avenue, 6
Phone Office: (383) 330-85-70 E-mail: vorop@ict.nsc.ru SPIN-code: 6550-0849Shokin Yuriy Ivanovich Dr. , Academician RAS, Professor Position: Scientific Director of the Institute Office: Federal Research Center for Information and Computational Technologies Address: 630090, Russia, Novosibirsk, Ac. Lavrentiev ave., 6
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Bibliography link: Senotrusova S.D., Voropaeva O.F., Shokin Y.I. Application of minimal mathematical models for the dynamics of the signaling pathway of the p53 - miRNA to the analysis of laboratory data // Computational technologies. 2020. V. 25. ¹ 6. P. 4-49
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