Modeling and Analysis of Biopathways Dynamics

Liu, Bing; Thiagarajan, P. S.

doi:10.1142/s0219720012310014

Cited by 18 publications

(12 citation statements)

References 95 publications

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“…Local sensitivity analysis was performed with a standard approach (76). Global sensitivity analysis was performed with an SMC-based MPSA method (77).…”

Section: Methodsmentioning

confidence: 99%

Innate immune memory and homeostasis may be conferred through crosstalk between the TLR3 and TLR7 pathways

Liu

Yang

et al. 2016

Sci. Signal.

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Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns (PAMPs) and stimulate the innate immune response through the production of cytokines. The innate immune response depends on the timing of encountering PAMPs, suggesting a short-term “memory.” In particular, activation of TLR3 appears to prime macrophages for the subsequent activation of TLR7, which leads to synergistically increased production of cytokines. By developing a calibrated mathematical model for the kinetics of TLR3 and TLR7 pathway crosstalk and providing experimental validation, we demonstrated the involvement of the Janus-activated kinase (JAK)–signal transducer and activator of transcription (STAT) pathway in controlling the synergistic production of cytokines. Signaling through this pathway played a dual role: It mediated the synergistic production of cytokines, thus boosting the immune response, and it also maintained homeostasis to avoid an excessive inflammatory response. Thus, we propose that the JAK-STAT pathway provides a cytokine rheostat mechanism, which enables macrophages to fine-tune their responses to multiple, temporally separated infection events involving the TLR3 and TLR7 pathways.

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“…Local sensitivity analysis was performed with a standard approach (76). Global sensitivity analysis was performed with an SMC-based MPSA method (77).…”

Section: Methodsmentioning

confidence: 99%

Innate immune memory and homeostasis may be conferred through crosstalk between the TLR3 and TLR7 pathways

Liu

Yang

et al. 2016

Sci. Signal.

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“…Instantaneous sensitivity is also known as 'logarithmic gain' in biochemical systems theory [33] or as the 'local sensitivity coefficient' in local parameter sensitivity analysis [34]. The response is ultrasensitive if |s| > 1, subsensitive if 0 < |s| < 1, desensitive if s = 0 and linear if |s| = 1.…”

Section: Sensitivity Analysismentioning

confidence: 99%

Reciprocal regulation between mRNA and microRNA enables a bistable switch that directs cell fate decisions

Tian

Zhang

et al. 2016

FEBS Letters

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Micro RNAs (miRNAs) serve as crucial post-transcriptional regulators in a variety of essential cell fate decisions. However, the contribution of mRNA-miRNA mutual regulation to bistability is not fully understood. In the present study, we built a set of mathematical models of mRNA-miRNA interactions and systematically analyzed the sensitivity of the response curves under various conditions. Our findings indicate that mRNA-miRNA reciprocal regulation could manifest ultrasensitivity to subserve the generation of bistability when equipped with a positive feedback loop. We also find that the region of bistability is expanded by a stronger competing endogenous mRNA. Interestingly, bistability can be generated without a feedback loop if multiple miRNA binding sites exist on a target mRNA. Thus, we demonstrate the importance of simple mRNA-miRNA reciprocal regulation in cell fate decisions.

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“…Computational modeling and analysis methods are playing a crucial role in understanding the complex dynamics of biological systems [1]. In this paper we address the parameter synthesis problem for hybrid models of biological systems.…”

Section: Introductionmentioning

confidence: 99%

Parameter Synthesis for Cardiac Cell Hybrid Models Using δ-Decisions

Liu

Kong

Gao

et al. 2014

Lecture Notes in Computer Science

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A central problem in systems biology is to identify parameter values such that a biological model satisfies some behavioral constraints (e.g., time series). In this paper we focus on parameter synthesis for hybrid (continuous/discrete) models, as many biological systems can possess multiple operational modes with specific continuous dynamics in each mode. These biological systems are naturally modeled as hybrid automata, most often with nonlinear continuous dynamics. However, hybrid automata are notoriously hard to analyze -even simple reachability for hybrid systems with linear differential dynamics is an undecidable problem. In this paper we present a parameter synthesis framework based on δ-complete decision procedures that sidesteps undecidability. We demonstrate our method on two highly nonlinear hybrid models of the cardiac cell action potential. The results show that our parameter synthesis framework is convenient and efficient, and it enabled us to select a suitable model to study and identify crucial parameter ranges related to cardiac disorders.

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Modeling and Analysis of Biopathways Dynamics

Cited by 18 publications

References 95 publications

Innate immune memory and homeostasis may be conferred through crosstalk between the TLR3 and TLR7 pathways

Innate immune memory and homeostasis may be conferred through crosstalk between the TLR3 and TLR7 pathways

Reciprocal regulation between mRNA and microRNA enables a bistable switch that directs cell fate decisions

Parameter Synthesis for Cardiac Cell Hybrid Models Using δ-Decisions

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