SearcharxivSearch

arXiv subjects

Matthew Wheeler

Publications and source records attributed to Matthew Wheeler.

14 recordsLinked to original sources

Permutation theory governs long-term dynamics of critical Boolean networks

Boolean networks are widely used to model gene regulatory Attractors of Boolean networks model stable gene-expression patterns, yet deriving their properties from network structure remains an open problem. We solve this problem for critical $K=1$ networks by showing that their feedback loops induce a permutation whose order bounds the average attractor length both above and below by universal constant factors. This correspondence allows classical results from combinatorics and number theory to be applied directly to Boolean network dynamics. We find three distinct asymptotic scales for both average and maximum attractor lengths: typical networks scale as $\exp[(1/8+o(1))(\ln N)^2]$, the ensemble means grow as $\exp[N^{1/3+o(1)}]$, and extremal networks attain $\exp[(1+o(1))\sqrt{N\ln N}]$. Thus, ensemble averages are governed by rare network realizations and are unrepresentative of typical dynamics.

q-bio.MN

Dynamics Decomposition of Boolean Networks: An algebraic foundation

Understanding the dynamics of Boolean networks is central to problems such as network reduction, design, control, and reverse engineering. As Boolean network models continue to grow in size and complexity, it becomes increasingly important to decompose networks into modules in a manner that is compatible with their dynamics. In this paper, we show that endowing the space of possible dynamics with a semiring structure enables a systematic decomposition of the dynamics of any Boolean network in terms of the dynamics of its constituent modules. This algebraic framework provides a systematic way to analyze how local dynamical behaviors combine to produce global dynamics. Our results establish a concrete algebraic foundation for network modularity and introduce new mathematical tools for the study of complex Boolean networks, and opens the door to the application of algebraic methods to problems of network analysis, decomposition, and control.

q-bio.QM

Upper bound for the stability of Boolean networks

Boolean networks, inspired by gene regulatory networks, were developed to understand the complex behaviors observed in biological systems, with network attractors corresponding to biological phenotypes or cell types. In this article, we present a proof for a conjecture by Williadsen, Triesch and Wiles about upper bounds for the stability of basins of attraction in Boolean networks. We further extend this result from a single basin of attraction to the entire network. Specifically, we demonstrate that the asymptotic upper bound for the robustness and the basin entropy of a Boolean network are negatively linearly related.

q-bio.MN

Categorical foundations of discrete dynamical systems

We develop categorical foundations of discrete dynamical systems, aimed at understanding how the structure of the system affects its dynamics. We introduce the notion of cycle sets to analyze attractors of a system, and use this to generalize multiple decomposition theorems of Kadelka, Veliz-Cuba, Murrugarra, and the last two authors from Boolean networks to arbitrary discrete dynamical systems.

math.DS

Bayesian non-linear subspace shrinkage using horseshoe priors

When modeling biological responses using Bayesian non-parametric regression, prior information may be available on the shape of the response in the form of non-linear function spaces that define the general shape of the response. To incorporate such information into the analysis, we develop a non-linear functional shrinkage (NLFS) approach that uniformly shrinks the non-parametric fitted function into a non-linear function space while allowing for fits outside of this space when the data suggest alternative shapes. This approach extends existing functional shrinkage approaches into linear subspaces to shrinkage into non-linear function spaces using a Taylor series expansion and corresponding updating of non-linear parameters. We demonstrate this general approach on the Hill model, a popular, biologically motivated model, and show that shrinkage into combined function spaces, i.e., where one has two or more non-linear functions a priori, is straightforward. We demonstrate this approach through synthetic and real data. Computational details on the underlying MCMC sampling are provided with data and analysis available in an online supplement.

stat.ME

Mixup Barcodes: Quantifying Geometric-Topological Interactions between Point Clouds

We combine standard persistent homology with image persistent homology to define a novel way of characterizing shapes and interactions between them. In particular, we introduce: (1) a mixup barcode, which captures geometric-topological interactions (mixup) between two point sets in arbitrary dimension; (2) simple summary statistics, total mixup and total percentage mixup, which quantify the complexity of the interactions as a single number; (3) a software tool for playing with the above. As a proof of concept, we apply this tool to a problem arising from machine learning. In particular, we study the disentanglement in embeddings of different classes. The results suggest that topological mixup is a useful method for characterizing interactions for low and high-dimensional data. Compared to the typical usage of persistent homology, the new tool is sensitive to the geometric locations of the topological features, which is often desirable.

math.AT

Modular control of Boolean network models

The concept of control is crucial for effectively understanding and applying biological network models. Key structural features relate to control functions through gene regulation, signaling, or metabolic mechanisms, and computational models need to encode these. Applications often focus on model-based control, such as in biomedicine or metabolic engineering. In a recent paper, the authors developed a theoretical framework of modularity in Boolean networks, which lead to a canonical semidirect product decomposition of these systems. In this paper, we present an approach to model-based control that exploits this modular structure, as well as the canalizing features of the regulatory mechanisms. We show how to identify control strategies from the individual modules, and we present a criterion based on canalizing features of the regulatory rules to identify modules that do not contribute to network control and can be excluded. For even moderately sized networks, finding global control inputs is computationally challenging. Our modular approach leads to an efficient approach to solving this problem. We apply it to a published Boolean network model of blood cancer large granular lymphocyte (T-LGL) leukemia to identify a minimal control set that achieves a desired control objective.

q-bio.MN

Modular Construction of Boolean Networks

Boolean networks have been used in a variety of settings, as models for general complex systems as well as models of specific systems in diverse fields, such as biology, engineering, and computer science. Traditionally, their properties as dynamical systems have been studied through simulation studies, due to a lack of mathematical structure. This paper uses a common mathematical technique to identify a class of Boolean networks with a "simple" structure and describes an algorithm to construct arbitrary extensions of a collection of simple Boolean networks. In this way, all Boolean networks can be obtained from a collection of simple Boolean networks as building blocks. The paper furthermore provides a formula for the number of extensions of given simple networks and, in some cases, provides a parametrization of those extensions. This has potential applications to the construction of networks with particular properties, for instance in synthetic biology, and can also be applied to develop efficient control algorithms for Boolean network models.

math.DS

User Perception and Actions Through Risk Analysis Concerning Cookies

A website browser cookie is a small file created by a web server upon visitation, which is placed in the user's browser directory to enhance the user's experience. However, first and third-party cookies have become a significant threat to users' privacy due to their data collection methods. To understand the users' perception of the risk of cookies and targeted advertisements, we conducted a user study through a control versus experimental group survey. Our goal was to gauge how user knowledge reflected their security and privacy preferences on the internet; thus, for the experimental group, we created a learning website and information videos through participatory design in a workshop with 15 participants. After that, by evaluating the responses of 68 participants through the survey, we analyzed user awareness of cookies, their privacy implications, and how risk communication can impact user behavior.

cs.CY

Decomposition of Boolean networks: An approach to modularity of biological systems

This paper presents the foundation for a decomposition theory for Boolean networks, a type of discrete dynamical system that has found a wide range of applications in the life sciences, engineering, and physics. Given a Boolean network satisfying certain conditions, there is a unique collection of subnetworks so that the network can be reconstructed from these subnetworks by an extension operation. The main result of the paper is that this structural decomposition induces a corresponding decomposition of the network dynamics. The theory is motivated by the search for a mathematical framework to formalize the hypothesis that biological systems are modular, widely accepted in the life sciences, but not well-defined and well-characterized. As an example of how dynamic modularity could be used for the efficient identification of phenotype control, the control strategies for the network can be found by identifying controls in its modules, one at a time.

math.DS

Activation Landscapes as a Topological Summary of Neural Network Performance

We use topological data analysis (TDA) to study how data transforms as it passes through successive layers of a deep neural network (DNN). We compute the persistent homology of the activation data for each layer of the network and summarize this information using persistence landscapes. The resulting feature map provides both an informative visual- ization of the network and a kernel for statistical analysis and machine learning. We observe that the topological complexity often increases with training and that the topological complexity does not decrease with each layer.

cs.LG

Topological actions via gauge variations of higher structures

In this note we provide a new perspective on the topological parts of several action functionals in string and M-theory. We show that rationally these can be viewed as large gauge transformations corresponding to variations of higher structures, such as String, Fivebrane, and Ninebrane structures.

hep-th

Variations of rational higher tangential structures

The study of higher tangential structures, arising from higher connected covers of Lie groups (String, Fivebrane, Ninebrane structures), require considerable machinery for a full description, especially for connections to geometry and applications. With utility in mind, in this paper we study these structures at the rational level and by considering Lie groups as a starting point for defining each of the higher structures, making close connection to $p_i$-structures. We indicatively call these (rational) Spin-Fivebrane and Spin-Ninebrane structures. We study the space of such structures and characterize their variations, which reveal interesting effects whereby variations of higher structures are arranged to systematically involve lower ones. We also study the homotopy type of the gauge group corresponding to bundles equipped with the higher rational structures that we define.

math.AT

Efficient Bayesian inference in stochastic chemical kinetic models using graphical processing units

A goal of systems biology is to understand the dynamics of intracellular systems. Stochastic chemical kinetic models are often utilized to accurately capture the stochastic nature of these systems due to low numbers of molecules. Collecting system data allows for estimation of stochastic chemical kinetic rate parameters. We describe a well-known, but typically impractical data augmentation Markov chain Monte Carlo algorithm for estimating these parameters. The impracticality is due to the use of rejection sampling for latent trajectories with fixed initial and final endpoints which can have diminutive acceptance probability. We show how graphical processing units can be efficiently utilized for parameter estimation in systems that hitherto were inestimable. For more complex systems, we show the efficiency gain over traditional CPU computing is on the order of 200. Finally, we show a Bayesian analysis of a system based on Michaelis-Menton kinetics.

stat.CO