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Incorporating Time Delays in Process Hitting Framework for Dynamical Modeling of Large Biological Regulatory Networks

机译:在大型生物管理网络动态建模的流程建模框架中纳入时间延迟

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摘要

Modeling and simulation of molecular systems helps in understanding the behavioral mechanism of biological regulation. Time delays in production and degradation of expressions are important parameters in biological regulation. Constraints on time delays provide insight into the dynamical behavior of a Biological Regulatory Network (BRN). A recently introduced Process Hitting (PH) Framework has been found efficient in static analysis of large BRNs, however, it lacks the inference of time delays and thus determination of their constraints associated with the evolution of the expression levels of biological entities of BRN is not possible. In this paper we propose a Hybrid Process Hitting scheme for introducing time delays in Process Hitting Framework for dynamical modeling and analysis of Large Biological Regulatory Networks. It provides valuable insights into the time delays corresponding to the changes in the expression levels of biological entities thus possibly helping in identification of therapeutic targets. The proposed framework is applied to a well-known BRNs of Bacteriophage λ and ERBB Receptor-regulated G1/S transition involved in the breast cancer to demonstrate the viability of our approach. Using the proposed approach, we are able to perform goal-oriented reduction of the BRN and also determine the constraints on time delays characterizing the evolution (dynamics) of the reduced BRN.
机译:分子系统的建模和仿真有助于理解生物调控的行为机制。生产和表达降解的时间延迟是生物调节中的重要参数。时间延迟的约束提供了对生物监管网络(BRN)动力学行为的洞察力。已经发现,最近引入的过程击中(PH)框架在大型BRN的静态分析中很有效,但是它缺乏时间延迟的推断,因此无法确定与BRN生物学实体表达水平的演变相关的约束条件。可能。在本文中,我们提出了一种混合流程插补方案,用于在流程插补框架中引入时间延迟,以便对大型生物监管网络进行动态建模和分析。它为与生物实体表达水平变化相对应的时间延迟提供了宝贵的见识,从而有可能有助于鉴定治疗靶标。拟议的框架应用于乳腺癌的噬菌体λ和ERBB受体调节的G1 / S过渡的知名BRN,以证明我们方法的可行性。使用提出的方法,我们能够执行面向目标的BRN减少,并且还可以确定对表征减少的BRN的演化(动态)的时间延迟的约束。

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