Bifurcation analysis of bistable and oscillatory dynamics in biological networks using the root‐locus method

Avcu, Neslihan; Güzeliş, Cüneyt

doi:10.1049/iet-syb.2019.0043

Cited by 7 publications

(7 citation statements)

References 29 publications

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“…Nevertheless, the existence of positive loops is far from being sufficient; a positive feedback loop does not guarantee bistability, and this property has to be quantitatively explored for each particular system in order to confirm the emergence of this property [23]. This switchlike behavior is recognized by bifurcation analysis (or phase plane analysis), namely, equilibrium point analysis, which includes studies related to the changes in the qualitative and quantitative structures of the equilibrium points depending on the changes in the model parameters [24]. At bifurcation points, a system's behavior may differ qualitatively depending on small changes in the bifurcation parameters (those model parameters that enable the system to switch from one steady state to the other) [25].…”

Section: Multistability Hysteresis and Ultrasensitivitymentioning

confidence: 99%

Multistability in Macrophage Activation Pathways and Metabolic Implications

Geiß

Salas

Guevara-Coto

et al. 2022

Cells

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Macrophages are innate immune cells with a dynamic range of reversible activation states including the classical pro-inflammatory (M1) and alternative anti-inflammatory (M2) states. Deciphering how macrophages regulate their transition from one state to the other is key for a deeper understanding of inflammatory diseases and relevant therapies. Common regulatory motifs reported for macrophage transitions, such as positive or double-negative feedback loops, exhibit a switchlike behavior, suggesting the bistability of the system. In this review, we explore the evidence for multistability (including bistability) in macrophage activation pathways at four molecular levels. First, a decision-making module in signal transduction includes mutual inhibitory interactions between M1 (STAT1, NF-KB/p50-p65) and M2 (STAT3, NF-KB/p50-p50) signaling pathways. Second, a switchlike behavior at the gene expression level includes complex network motifs of transcription factors and miRNAs. Third, these changes impact metabolic gene expression, leading to switches in energy production, NADPH and ROS production, TCA cycle functionality, biosynthesis, and nitrogen metabolism. Fourth, metabolic changes are monitored by metabolic sensors coupled to AMPK and mTOR activity to provide stability by maintaining signals promoting M1 or M2 activation. In conclusion, we identify bistability hubs as promising therapeutic targets for reverting or blocking macrophage transitions through modulation of the metabolic environment.

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Section: Multistability Hysteresis and Ultrasensitivitymentioning

confidence: 99%

Multistability in Macrophage Activation Pathways and Metabolic Implications

Geiß

Salas

Guevara-Coto

et al. 2022

Cells

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show abstract

“…Nevertheless, the existence of positive loops is far from being sufficient; a positive feedback loop does not guarantee bistability and this property has to be quantitatively explored for each particular system in order to confirm the emergence of this property [28]. This switch -like behavior is recognized by bifurcation analysis (or phase plane analysis), namely the equilibrium point analysis, which includes the studies related to the changes in the qualitative and quantitative structures of the equilibrium points depending on the changes in the model parameters [29]. At bifurcation points a system's behavior may differ qualitatively depending on small changes in the bifurcation parameters: those model parameters that enable the system to switch from one steady state to the other [30].…”

Section: Current Evidence Pointing To Bistability In Macrophage Programsmentioning

confidence: 99%

Bistability in macrophage polarization and metabolic implications

Geiß¹,

Salas²,

Guevara-Coto³

et al. 2021

Preprint

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Macrophages are essential innate immune cells characterized by a high diversity and plasticity. In vitro, their full dynamic range of activation profiles include the classical pro-inflammatory (M1) and the alternative anti-inflammatory (M2) program. Bistability usually arises in biological systems that contain a positive-feedback loop or a mutually inhibitory, double-negative-feedback loop, which are common regulatory motifs reported for macrophage transitions from one activation state to the other one. This switch-like behavior of macrophage is observed at four different levels. First, a decision-making module in signal transduction includes mutual inhibitory interactions between M1 (STAT1 and NF-KB/p50-p65) and M2 (STAT3 and NF-KB/p50-p50) signaling pathways. Second, a switch-like behavior at the gene expression level includes complex network motifs of transcription factors and miRNAs. Third, those changes impact metabolic gene expression leading to several switches in energy production, NADPH and ROS production, TCA cycle functionality, biosynthesis and nitrogen metabolism. Fourth, metabolic changes are monitored by specialized metabolic sensors coupled to AMPK and mTOR activity to provide stability by maintaining the signals to promote either M1 or M2 activation. The targeting of robust molecular switches has the potential to treat a broad range of widespread diseases such as sepsis, cancer or chronic inflammatory diseases.

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“…BBRESD data was divided into 60, 20, and 20% and was used for training, testing, and validating the ANN topology. An optimal number of hidden layers were selected based on the lowest mean square error (MSE) value using hit and train technique [41].…”

Section: Ann Modelling and Ann-ga Optimizationmentioning

confidence: 99%

Optimization and characterization of pectin recovered from Persea americana peel using statistical and non-statistical techniques

Sivamani¹,

Binnal²,

Roy³

et al. 2021

Biomass Conv. Bioref.

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The intention of this present study is to optimize the recovery of pectin from Persea americana peel (PAP) examining four independent process variables (pH, solvent to substrate ratio (SSR) (ml/g), agitation time (AGT) (h), and agitation speed (AGS) (rpm)) and compare the pectin recovery (PR) using statistical (Box-Behnken response surface design (BBRESD)) and non-statistical (artificial neural network (ANN) with genetic algorithm (GA)) methods. Optimal condition derived in ANN-GA (pH of 1.9, SSR of 16 ml/g, AGT of 2.1 h, AGS of 99 rpm, and PR of 90.59%) has forecast PR very precisely than BBRESD (pH of 2, SSR of 14 ml/g, AGT of 2 h, AGS of 100 rpm, and PR of 85.44%). Extrapolative capacities of two methods were examined by several statistical restraints. Structural analysis (FT-IR and XRD) of PR was exhibited that highly esterified and amorphous nature of pectin was recovered from PAP. Recovered pectin was melted at the temperature of 258.5 °C which was similar to commercial pectin. SEM observations revealed that recovered pectin was flake and spherical particle. The results of this work suggested that pectin from PAP is one of the good sources to recover pectin with good quality as commercial pectin and used as a food ingredient.

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Bifurcation analysis of bistable and oscillatory dynamics in biological networks using the root‐locus method

Cited by 7 publications

References 29 publications

Multistability in Macrophage Activation Pathways and Metabolic Implications

Multistability in Macrophage Activation Pathways and Metabolic Implications

Bistability in macrophage polarization and metabolic implications

Optimization and characterization of pectin recovered from Persea americana peel using statistical and non-statistical techniques

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