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EURASIP Journal on Bioinformatics and Systems Biology

, 2012:19

First Online: 26 December 2012Received: 30 April 2012Accepted: 12 November 2012

Abstract

Drug discovery today is a complex, expensive, and time-consuming process with high attrition rate. A more systematic approach is needed to combine innovative approaches in order to lead to more effective and efficient drug development. This article provides systematic mathematical analysis and dynamical modeling of drug effect under gene regulatory network contexts. A hybrid systems model, which merges together discrete and continuous dynamics into a single dynamical model, is proposed to study dynamics of the underlying regulatory network under drug perturbations. The major goal is to understand how the system changes when perturbed by drugs and give suggestions for better therapeutic interventions. A realistic periodic drug intake scenario is considered, drug pharmacokinetics and pharmacodynamics information being taken into account in the proposed hybrid systems model. Simulations are performed using MATLAB-SIMULINK to corroborate the analytical results.

KeywordsDrug effect Hybrid systems PK-PD Gene regulatory network GRN Dosing regimens Electronic supplementary materialThe online version of this article doi:10.1186-1687-4153-2012-19 contains supplementary material, which is available to authorized users.

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Autor: Xiangfang Li - Lijun Qian - Edward R Dougherty

Fuente: https://link.springer.com/



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