College of Letters & Science

Permanent URI for this communityhttps://scholarworks.montana.edu/handle/1/37

The College of Letters and Science, the largest center for learning, teaching and research at Montana State University, offers students an excellent liberal arts and sciences education in nearly 50 majors, 25 minors and over 25 graduate degrees within the four areas of the humanities, natural sciences, mathematics and social sciences.

Browse

Search Results

Now showing 1 - 9 of 9
  • Thumbnail Image
    Item
    Extending Combinatorial Regulatory Network Modeling to Include Activity Control and Decay Modulation
    (Society for Industrial & Applied Mathematics, 2022-09) Cummins, Bree; Gameiro, Marcio; Gedeon, Tomas; Kepley, Shane; Mischaikow, Konstantin; Zhang, Lun
    Understanding how the structure of within-system interactions affects the dynamics of the system is important in many areas of science. We extend a network dynamics modeling platform DSGRN, which combinatorializes both dynamics and parameter space to construct finite but accurate summaries of network dynamics, to new types of interactions. While the standard DSGRN assumes that each network edge controls the rate of abundance of the target node, the new edges may control either activity level or a decay rate of its target. While motivated by processes of post-transcriptional modification and ubiquitination in systems biology, our extension is applicable to the dynamics of any signed directed network.
  • Thumbnail Image
    Item
    Genetic networks encode secrets of their past
    (Elsevier BV, 2022-03) Crawford-Kahrl, Peter; Nerem, Robert R.; Cummins, Bree; Gedeon, Tomas
    Research shows that gene duplication followed by either repurposing or removal of duplicated genes is an important contributor to evolution of gene and protein interaction networks. We aim to identify which characteristics of a network can arise through this process, and which must have been produced in a different way. To model the network evolution, we postulate vertex duplication and edge deletion as evolutionary operations on graphs. Using the novel concept of an ancestrally distinguished subgraph, we show how features of present-day networks require certain features of their ancestors. In particular, ancestrally distinguished subgraphs cannot be introduced by vertex duplication. Additionally, if vertex duplication and edge deletion are the only evolutionary mechanisms, then a graph’s ancestrally distinguished subgraphs must be contained in all of the graph’s ancestors. We analyze two experimentally derived genetic networks and show that our results accurately predict lack of large ancestrally distinguished subgraphs, despite this feature being statistically improbable in associated random networks. This observation is consistent with the hypothesis that these networks evolved primarily via vertex duplication. The tools we provide open the door for analyzing ancestral networks using current networks. Our results apply to edge-labeled (e.g. signed) graphs which are either undirected or directed.
  • Thumbnail Image
    Item
    Using extremal events to characterize noisy time series
    (2020-02) Berry, Eric; Cummins, Bree; Nerem, Robert R.; Smith, Lauren M.; Haase, Steven B.; Gedeon, Tomas
    Experimental time series provide an informative window into the underlying dynamical system, and the timing of the extrema of a time series (or its derivative) contains information about its structure. However, the time series often contain significant measurement errors. We describe a method for characterizing a time series for any assumed level of measurement error 𝜀 by a sequence of intervals, each of which is guaranteed to contain an extremum for any function that 𝜀-approximates the time series. Based on the merge tree of a continuous function, we define a new object called the normalized branch decomposition, which allows us to compute intervals for any level 𝜀. We show that there is a well-defined total order on these intervals for a single time series, and that it is naturally extended to a partial order across a collection of time series comprising a dataset. We use the order of the extracted intervals in two applications. First, the partial order describing a single dataset can be used to pattern match against switching model output (Cummins et al. in SIAM J Appl Dyn Syst 17(2):1589–1616, 2018), which allows the rejection of a network model. Second, the comparison between graph distances of the partial orders of different datasets can be used to quantify similarity between biological replicates.
  • Thumbnail Image
    Item
    Comparison of Combinatorial Signatures of Global Network Dynamics Generated by Two Classes of ODE Models
    (2019-04) Crawford-Kahrl, Peter; Cummins, Bree; Gedeon, Tomas
    Modeling the dynamics of biological networks introduces many challenges, among them the lack of first principle models, the size of the networks, and difficulties with parameterization. Discrete time Boolean networks and related continuous time switching systems provide a computationally accessible way to translate the structure of the network to predictions about the dynamics. Recent work has shown that the parameterized dynamics of switching systems can be captured by a combinatorial object, called a Dynamic Signatures Generated by Regulatory Networks (DSGRN) database, that consists of a parameter graph characterizing a finite parameter space decomposition, whose nodes are assigned a Morse graph that captures global dynamics for all corresponding parameters. We show that for a given network there is a way to associate the same type of object by considering a continuous time ODE system with a continuous right-hand side, which we call an L-system. The main goal of this paper is to compare the two DSGRN databases for the same network. Since the L-systems can be thought of as perturbations (not necessarily small) of the switching systems, our results address the correspondence between global parameterized dynamics of switching systems and their perturbations. We show that, at corresponding parameters, there is an order preserving map from the Morse graph of the switching system to that of the L-system that is surjective on the set of attractors and bijective on the set of fixed-point attractors. We provide important examples showing why this correspondence cannot be strengthened.
  • Thumbnail Image
    Item
    DSGRN: Examining the Dynamics of Families of Logical Models
    (2018-06) Cummins, Bree; Gedeon, Tomas; Harker, Shaun; Mischaikow, Konstantin
    We present a computational tool DSGRN for exploring the dynamics of a network by computing summaries of the dynamics of switching models compatible with the network across all parameters. The network can arise directly from a biological problem, or indirectly as the interaction graph of a Boolean model. This tool computes a finite decomposition of parameter space such that for each region, the state transition graph that describes the coarse dynamical behavior of a network is the same. Each of these parameter regions corresponds to a different logical description of the network dynamics. The comparison of dynamics across parameters with experimental data allows the rejection of parameter regimes or entire networks as viable models for representing the underlying regulatory mechanisms. This in turn allows a search through the space of perturbations of a given network for networks that robustly fit the data. These are the first steps toward discovering a network that optimally matches the observed dynamics by searching through the space of networks.
  • Thumbnail Image
    Item
    Global dynamics for switching systems and their extensions by linear differential equations
    (2018-11) Huttinga, Zane; Cummins, Bree; Gedeon, Tomas; Mischaikow, Konstantin
    Switching systems use piecewise constant nonlinearities to model gene regulatory networks. This choice provides advantages in the analysis of behavior and allows the global description of dynamics in terms of Morse graphs associated to nodes of a parameter graph. The parameter graph captures spatial characteristics of a decomposition of parameter space into domains with identical Morse graphs. However, there are many cellular processes that do not exhibit threshold-like behavior and thus are not well described by a switching system. We consider a class of extensions of switching systems formed by a mixture of switching interactions and chains of variables governed by linear differential equations. We show that the parameter graphs associated to the switching system and any of its extensions are identical. For each parameter graph node, there is an order-preserving map from the Morse graph of the switching system to the Morse graph of any of its extensions. We provide counterexamples that show why possible stronger relationships between the Morse graphs are not valid.
  • Thumbnail Image
    Item
    Combinatorial Representation of Parameter Space for Switching Networks
    (2016-11) Cummins, Bree; Harker, Shaun; Mischaikow, Konstantin; Mok, Kafung; Gedeon, Tomas
    We describe the theoretical and computational framework for the Dynamic Signatures Generated by Regulatory Networks (DSGRN) database. The motivation stems from an urgent need to understand the global dynamics of biologically relevant signal transduction/gene regulatory networks that have at least 5 to 10 nodes, involve multiple interactions, and have decades of parameters. The input to the database computations is a regulatory network, i.e., a directed graph with edges indicating up or down regulation. A computational model based on switching networks is generated from the regulatory network. The phase space dimension of this model equals the number of nodes and the associated parameter space consists of one parameter for each node (a decay rate) and three parameters for each edge (low level of expression, high level of expression, and threshold at which expression levels change). Since the nonlinearities of switching systems are piecewise constant, there is a natural decomposition of phase space into cells from which the dynamics can be described combinatorially in terms of a state transition graph. This in turn leads to a compact representation of the global dynamics called an annotated Morse graph that identifies recurrent and nonrecurrent dynamics. The focus of this paper is on the construction of a natural computable finite decomposition of parameter space into domains where the annotated Morse graph description of dynamics is constant. We use this decomposition to construct an SQL database that can be effectively searched for dynamical signatures such as bistability, stable or unstable oscillations, and stable equilibria. We include two simple 3-node networks to provide small explicit examples of the type of information stored in the DSGRN database. To demonstrate the computational capabilities of this system we consider a simple network associated with p53 that involves 5 nodes and a 29-dimensional parameter space.
  • Thumbnail Image
    Item
    Convergence Properties of Posttranslationally Modified Protein-Protein Switching Networks with Fast Decay Rates
    (2016-06) Fan, G.; Cummins, Bree; Gedeon, Tomas
    A significant conceptual difficulty in the use of switching systems to model regulatory networks is the presence of so-called "black walls" co-dimension 1 regions of phase space with a vector field pointing inward on both sides of the hyperplane. Black walls result from the existence of direct negative self-regulation in the system. One biologically inspired way of removing black walls is the introduction of intermediate variables that mediate the negative self-regulation. In this paper, we study such a perturbation. We replace a switching system with a higher-dimensional switching system with rapidly decaying intermediate proteins, and compare the dynamics between the two systems. We find that the while the individual solutions of the original system can be approximated for a finite time by solutions of a sufficiently close perturbed system, there are always solutions that are not well approximated for any fixed perturbation. We also study a particular example, where global basins of attraction of the perturbed system have a strikingly different form than those of the original system. We perform this analysis using techniques that are adapted to dealing with non-smooth systems.
  • Thumbnail Image
    Item
    On the Efficacy of State Space Reconstruction Methods in Determining Causality
    (2015-03) Cummins, Bree; Gedeon, Tomas; Spendlove, Kelly T.
    We present a theoretical framework for inferring dynamical interactions between weakly or moderately coupled variables in systems where deterministic dynamics plays a dominating role. The variables in such a system can be arranged into an interaction graph, which is a set of nodes connected by directed edges wherever one variable directly drives another. In a system of ordinary differential equations, a variable $x$ directly drives $y$ if it appears nontrivially on the right-hand side of the equation for the derivative of $y$. Ideally, given time series measurements of the variables in a system, we would like to recover the interaction graph. We introduce a comprehensive theory showing that the transitive closure of the interaction graph is the best outcome that can be obtained from state space reconstructions in a purely deterministic system. Our work depends on extensions of Takens\' theorem and the results of Sauer et al. [J. Stat. Phys., 65 (1991), pp. 579--616] that characterize the properties of time-delay reconstructions of invariant manifolds and attractors. Along with the theory, we discuss practical implementations of our results. One method for empirical recovery of the interaction graph is presented by Sugihara et al. [Science, 338 (2012), pp. 496--500], called convergent cross-mapping. We show that the continuity detection algorithm of Pecora et al. [Phys. Rev. E, 52 (1995), pp. 3420--3439] is a viable alternative to convergent cross-mapping that is more consistent with the underlying theory. We examine two examples of dynamical systems for which we can recover the transitive closure of the interaction graph using the continuity detection technique. The strongly connected components of the recovered graph represent distinct dynamical subsystems coupled through one-way driving relationships that may correspond to causal relationships in the underlying physical scenario.
Copyright (c) 2002-2022, LYRASIS. All rights reserved.