arXiv subjects

Patrick Vincent N. Lubenia

Publications and source records attributed to Patrick Vincent N. Lubenia.

9 recordsLinked to original sources

arXiv2026

The finest decompositions' architecture of a reaction network

Biochemical and environmental modeling typically relies on reaction networks to represent complex transformations. While the Linkage Class Decomposition (LCD) partitions networks based on visual standard connectivity, it often misaligns with the algebraic properties governing long-term dynamics. This work establishes the Finest Decompositions' Architecture (FDA) framework by analyzing hierarchical relationships between the LCD and two algebraic structures: the Finest Independent Decomposition (FID) and the Finest Incidence-Independent Decomposition (FIID). These algebraic decompositions serve as the respective building blocks for characterizing general equilibria and complex-balanced equilibria of a reaction network. Under the partial order of "coarsens to," we categorize reaction networks into six architectures, distinguishing three subclasses of Independent Linkage Classes (ILC) from three subclasses of Dependent Linkage Classes (DLC). To facilitate the classification, we introduce the Deficiency Difference (Delta), measuring the discrepancy between total and subnetwork deficiencies, and the Common Complexes Cardinality CC of the FID. Results show that Delta uniquely identifies all the ILC classes and one DLC subclass, while CC distinguishes the remaining DLC subclasses. A number of results on mass action systems such as the Deficiency One Theorem as well as on power law systems essentially rely on the ILC property of the underlying networks. These suggest that the FDA classification of ILC and DLC networks signify a certain alignment of both structural and kinetic attributes. This work opens up direction for the study of the structure and equilibria analysis of reaction networks across diverse decomposition architectures.

q-bio.MN↗

arXiv2025

Quickest Change Detection with Cost-Constrained Experiment Design

In the classical quickest change detection problem, an observer performs a single experiment to monitor a stochastic process. The goal in the classical problem is to detect a change in the statistical properties of the process, with the minimum possible delay, subject to a constraint on the rate of false alarms. This paper considers the case where, at each observation time, the decision-maker must choose between multiple experiments with varying information qualities and costs. The change can be detected using any of the experiments. The goal here is to detect the change with the minimum delay, subject to constraints on the rate of false alarms and the fraction of time each experiment is performed before the time of change. The constraint on the fraction of time can be used to control the overall cost of using the system of experiments. An algorithm called the two-experiment cumulative sum (2E-CUSUM) algorithm is first proposed to solve the problem when there are only two experiments. The algorithm for the case of multiple experiments, starting with three experiments, is then designed iteratively using the 2E-CUSUM algorithm. Two key ideas used in the design are the scaling of undershoots and the truncation of tests. The multiple-experiment algorithm can be designed to satisfy the constraints and can achieve the delay performance of the experiment with the highest quality within a constant. The important concept of data efficiency, where the observer has the choice of not performing any experiment, is explored as well.

eess.SP↗

arXiv2024

Comparison of reaction networks of insulin signaling

Understanding the insulin signaling cascade provides insights on the underlying mechanisms of biological phenomena such as insulin resistance, diabetes, Alzheimer's disease, and cancer. For this reason, previous studies utilized chemical reaction network theory to perform comparative analyses of reaction networks of insulin signaling in healthy (INSMS: INSulin Metabolic Signaling) and diabetic cells (INRES: INsulin RESistance). This study extends these analyses using various methods which give further insights regarding insulin signaling. Using embedded networks, we discuss evidence of the presence of a structural "bifurcation" in the signaling process between INSMS and INRES. Concordance profiles of INSMS and INRES show that both have a high propensity to remain monostationary. Moreover, the concordance properties allow us to present heuristic evidence that INRES has a higher level of stability beyond its monostationarity. Finally, we discuss a new way of analyzing reaction networks through network translation. This method gives rise to three new insights: (i) each stoichiometric class of INSMS and INRES contains a unique positive equilibrium; (ii) any positive equilibrium of INSMS is exponentially stable and is a global attractor in its stoichiometric class; and (iii) any positive equilibrium of INRES is locally asymptotically stable. These results open up opportunities for collaboration with experimental biologists to understand insulin signaling better.

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arXiv2024

A decomposition-based approach for deriving positive steady states of a class of chemical reaction networks with non-mass-action kinetics

Steady states are frequently used to investigate the long-term behaviors of (bio)-chemical systems. Recently, there has been a growing interest in network-based approaches due to their efficiency in deriving parametrizations of positive steady states in systems with mass-action kinetics. In this study, we extend this approach to derive positive steady states in networks under non-mass-action kinetics, specifically mixed kinetics. In a system with mixed kinetics, some reactions {may follow} mass-action kinetics, while others in the same network follow different rate laws, such as quotient rate laws. An example of such complexity is evident in a mathematical model of the insulin signaling pathway in type 2 diabetes. To compute its positive {steady states}, we adapt our existing network decomposition approach, originally designed for mass-action kinetics, to handle networks with non-mass-action kinetics. This approach involves breaking down a given network into smaller, independent subnetworks to derive the positive steady states of each subnetwork separately. These individual steady states are then combined to obtain the positive steady states of the entire network. This strategy makes computations more manageable for complex and large networks. More importantly, this method could separate reactions with purely mass-action kinetics into certain subnetworks from those that follow different rate laws. We also present an illustrative example that provides insights into methods for transforming networks with mixed kinetics into their associated mass-action systems.

math.DS↗

arXiv2024

Embedding-based comparison of reaction networks of Wnt signaling

This work introduces a new method for comparing two reaction networks of the same or closely related systems through their embedded networks in terms of the shared set of species. Hence, we call this method the Common Species Embedded Networks (CSEN) analysis. Using this approach, we conduct a comparison of existing reaction networks associated with Wnt signaling models (Lee, Schmitz, MacLean, and Feinberg) that we have identified. The analysis yields three important results for these Wnt models. First, the CSEN analysis of the Lee (mono-stationary) and Feinberg (multi-stationary) shows a strong similarity, justifying the study of the Feinberg model, which was a modified Lee model constructed to study an important network property called "concordance". It also challenge the absoluteness of discrimination of the models into mono-stationarity versus multi-stationarity, which is a main result of Maclean et al. (PNAS USA 2015). Second, the CSEN analysis provides evidence supporting a strong similarity between the Schmitz and MacLean models, as indicated by the "proximate equivalence" that we have identified. Third, the analysis underscores the absence of a comparable relationship between the Feinberg and MacLean models, highlighting distinctive differences between the two. Thus, our approach could be a useful tool to compare mathematical models of the same or closely related systems.

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arXiv2024

Equilibria decomposition-based comparison of reaction networks of Wnt signaling

The Wnt signaling pathway plays a critical role in various biochemical processes, including embryonic development, tissue homeostasis, and cancer progression. In this paper, we conduct a comparative analysis of $β$-catenin-dependent Wnt signaling reaction networks, which we refer to as the Feinberg, Schmitz, and MacLean models, based on the previous study by MacLean et al. (PNAS USA 2015). Our analysis is based on the (unique) finest independent decomposition (FID) of each reaction network and our comparative techniques include equilibria parametrizations (EP) and the newly developed methods of Common Reactions Equilibria (CORE) analysis and Concordance Profile (CP) analysis. Our investigation yields three interesting results concerning the equilibria sets of these models. Firstly, we explore the concept of absolute concentration robustness (ACR), wherein a system exhibits ACR in a specific species if the equilibrium value for that species is the same for any positive equilibrium. Through ACR analysis employing FID and EP, we observe that both the Schmitz and MacLean models lack ACR, whereas the Feinberg model demonstrates ACR in a single species. Second, our analyses using FID and CORE reveal important relationships within the equilibria sets of the augmented Schmitz and MacLean models. Furthermore, FID and CORE identify the lack of a substantial relationship between the equilibria sets of the Feinberg and MacLean models. Hence, these methods detect subtle differences between the Feinberg and MacLean models and also between the Schmitz and MacLean models, which are not evident in the standard reaction network analysis. Finally, based on the concordance levels, CP analysis indicates that the MacLean and Schmitz models are more similar than the MacLean and Feinberg models.

math.DS↗

arXiv2023

Comparative Analysis of Kinetic Realizations of Insulin Signaling

Several studies have developed dynamical models to understand the underlying mechanisms of insulin signaling, a signaling cascade that leads to the translocation of glucose, the human body's main source of energy. Fortunately, reaction network analysis allows us to extract properties of dynamical systems without depending on their model parameter values. This study focuses on the comparison of insulin signaling in healthy state (INSMS or INSulin Metabolic Signaling) and in type 2 diabetes (INRES or INsulin RESistance) using reaction network analysis. The analysis uses network decomposition to identify the different subsystems involved in insulin signaling (e.g., insulin receptor binding and recycling, GLUT4 translocation, and ERK signaling pathway, among others). Furthermore, results show that INSMS and INRES are similar with respect to some network, structo-kinetic, and kinetic properties. Their differences, however, provide insights into what happens when insulin resistance occurs. First, the variation in the number of species involved in INSMS and INRES suggests that when irregularities occur in the insulin signaling pathway, other complexes (and, hence, other processes) get involved, characterizing insulin resistance. Second, the loss of concordance exhibited by INRES suggests less restrictive interplay between the species involved in insulin signaling, leading to unusual activities in the signaling cascade. Lastly, GLUT4 losing its absolute concentration robustness in INRES may signify that the transporter has lost its reliability in shuttling glucose to the cell, inhibiting efficient cellular energy production. This study also suggests possible applications of the equilibria parametrization and network decomposition, resulting from the analysis, to potentially establish absolute concentration robustness in a species.

q-bio.MN↗

arXiv2022

Reaction Network Analysis of Metabolic Insulin Signaling

Absolute concentration robustness (ACR) and concordance are novel concepts in the theory of robustness and stability within Chemical Reaction Network Theory. In this paper, we have extended Shinar and Feinberg's reaction network analysis approach to the insulin signaling system based on recent advances in decomposing reaction networks. We have shown that the network with 20 species, 35 complexes, and 35 reactions is concordant, implying at most one positive equilibrium in each of its stoichiometric compatibility class. We have obtained the system's finest independent decomposition consisting of 10 subnetworks, a coarsening of which reveals three subnetworks which are not only functionally but also structurally important. Utilizing the network's deficiency-oriented coarsening, we have developed a method to determine positive equilibria for the entire network. Our analysis has also shown that the system has ACR in 8 species all coming from a deficiency zero subnetwork. Interestingly, we have shown that, for a set of rate constants, the insulin-regulated glucose transporter GLUT4 (important in glucose energy metabolism), has stable ACR.

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arXiv2021

Concentration Robustness in LP Kinetic Systems

For a reaction network with species set $\mathscr{S}$, a log-parametrized (LP) set is a non-empty set of the form $E(P, x^*) = \{x \in \mathbb{R}^\mathscr{S}_> \mid \log x - \log x^* \in P^\perp\}$ where $P$ (called the LP set's flux subspace) is a subspace of $\mathbb{R}^\mathscr{S}$, $x^*$ (called the LP set's reference point) is a given element of $\mathbb{R}^\mathscr{S}_>$, and $P^\perp$ (called the LP set's parameter subspace) is the orthogonal complement of $P$. A network with kinetics $K$ is a positive equilibria LP (PLP) system if its set of positive equilibria is an LP set. Analogously, it is a complex balanced equilibria LP (CLP) system if its set of complex balanced equilibria is an LP set. An LP kinetic system is a PLP or CLP system. This paper studies concentration robustness of a species on subsets of equilibria. We present the "species hyperplane criterion", a necessary and sufficient condition for absolute concentration robustness (ACR) for a species of a PLP system. An analogous criterion holds for balanced concentration robustness (BCR) for species of a CLP system. These criteria also lead to interesting necessary properties of LP systems with concentration robustness. Furthermore, we show that PLP and CLP power law systems with Shinar-Feinberg reaction pairs in species $X$ in a linkage class have ACR and BCR in $X$, respectively. This leads to a broadening of the "low deficiency building blocks" framework to include LP systems of Shinar-Feinberg type with arbitrary deficiency. Finally, we apply our results to species concentration robustness in LP systems with poly-PL kinetics.

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