A Static Analysis ofWnt/β-Catenin andWnt/Ca²⁺Biological Regulatory Networks for ARVC Using Automata Network Model

Abstract

The Wnt-activated β-catenin and Ca 2+ ions play a critical role in the regulation of physiology of cardiomyocytes. The dysregulation of both the components causes the replacement of myocardial mass right ventricle with fibrous and adipose tissue which results in the condition of Arrhythmogenic Right ventricular Cardiomyopathy (ARVC). The major hurdle in ARVC treatment is lack of effective therapies targeting the underlying root molecular biomarkers of pathogenesis. Despite major advancements in interpreting the mechanism of ARVC etiology, the dynamics of molecular links in underlying biological machinery are still being delineated. Previously, formal methods based computational modeling techniques including kinetic logic, Petri Nets, hybrid automata and static analysis have greatly contributed in increasing our comprehension to decipher the molecular systems dynamics. It has allowed the identification of biomarkers which can be utilized for target-based therapies owing to meticulous biological abstractions along with implementing reference map that confines together the discrete biological insights. In this study, we have performed the static analysis of the Biological Regulatory Networks (BRNs) of the Wnt/β-catenin and Wnt/Ca 2+ signaling pathways to identify the significant biomarkers for ARVC. The abstracted qualitative models of afore mentioned BRNs are first constructed in GINsim software tool and then these models are converted into Automata Network (ANs) Models using Pint software tool. The fix point analysis is performed which contributed in pinpointing the possible therapeutic strategies for ARVC treatment by identification of drug targets such as Gsk3, Ck1 and Axin in Wnt/β-catenin AN and Bak & Bax, Parp, mCalpain, JNk and CIn in Wnt/Ca 2+ AN. Moreover, the Bcl2 gene is identified as novel therapeutic remedy in both the ANs of ARVC. The Bcl2 gene prevents the cardiac apoptosis via positive regulation of Wnt in Wnt/β-catenin AN and through inhibition of Bak & Bax (apoptotic component) in Wnt/Ca 2+ AN.The current study tends to fulfill the scientific gap between wet lab studies and provides cost effective and time saving computational strategies for an effectual treatment for deadly diseases like ARVC.

Static Analysis of Dengue Biological Regulatory Network’s

“…The Dengue modeling methodology was thoroughly considered in search of the method and procedure cross framework implementation for the static analysis of the dengue model BRN signaling pathways, static analysis of the dengue model pathway is represented in the logical instruction/parameters striving in the study to showing the analysis of different frameworks and explained in the following ways [11].…”

“…Automata means "Something that works automatically". An Automata Network is a collection of the following here [11,14]. [16].…”

“…Within the confines of a process, a framework to perform the fixed-point analysis, the fix-point states considered in the graph model can be activated and inhibited, to control all the graph model fix-point nodes [11,17]. This method is crucial in determining the characteristics of a cell state.…”

“…If removing every edge from G causes G to disconnect, then the subset 'E' of E is referred to as a cut set of G. A graph is said to be disconnected if a certain number of its edges are removed; in this case, the removed edges are referred to as the cut set of the graph. Jump to the site [11].…”

“…Static analysis and modeling of BRN of the dengue pathway of longevity to perceive homeostasis and stable state [11].…”