ADAM: Analysis of Discrete Models of Biological Systems Using Computer Algebra

Background: Many biological systems are modeled qualitatively with discrete models, such as probabilistic Boolean networks, logical models, Petri nets, and agent-based models, with the goal to gain a better understanding of the system. The computational complexity to analyze the complete dynamics of these models grows exponentially in the number of variables, which impedes working with complex models. Although there exist sophisticated algorithms to determine the dynamics of discrete models, their implementations usually require labor-intensive formatting of the model formulation, and they are oftentimes not accessible to users without programming skills. Efficient analysis methods are needed that are accessible to modelers and easy to use. Method: By converting discrete models into algebraic models, tools from computational algebra can be used to analyze their dynamics. Specifically, we propose a method to identify attractors of a discrete model that is equivalent to solving a system of polynomial equations, a long-studied problem in computer algebra. Results: A method for efficiently identifying attractors, and the web-based tool Analysis of Dynamic Algebraic Models (ADAM), which provides this and other analysis methods for discrete models. ADAM converts several discrete model types automatically into polynomial dynamical systems and analyzes their dynamics using tools from computer algebra. Based on extensive experimentation with both discrete models arising in systems biology and randomly generated networks, we found that the algebraic algorithms presented in this manuscript are fast for systems with the structure maintained by most biological systems, namely sparseness, i.e., while the number of nodes in a biological network may be quite large, each node is affected only by a small number of other nodes, and robustness, i.e., small number of attractors

Entropy of complex relevant components of Boolean networks

Boolean network models of strongly connected modules are capable of capturing the high regulatory complexity of many biological gene regulatory circuits. We study numerically the previously introduced basin entropy, a parameter for the dynamical uncertainty or information storage capacity of a network as well as the average transient time in random relevant components as a function of their connectivity. We also demonstrate that basin entropy can be estimated from time-series data and is therefore also applicable to non-deterministic networks models.Comment: 8 pages, 6 figure

A micropower centroiding vision processor

Published versio

Compositionality, stochasticity and cooperativity in dynamic models of gene regulation

We present an approach for constructing dynamic models for the simulation of gene regulatory networks from simple computational elements. Each element is called a ``gene gate'' and defines an input/output-relationship corresponding to the binding and production of transcription factors. The proposed reaction kinetics of the gene gates can be mapped onto stochastic processes and the standard ode-description. While the ode-approach requires fixing the system's topology before its correct implementation, expressing them in stochastic pi-calculus leads to a fully compositional scheme: network elements become autonomous and only the input/output relationships fix their wiring. The modularity of our approach allows to pass easily from a basic first-level description to refined models which capture more details of the biological system. As an illustrative application we present the stochastic repressilator, an artificial cellular clock, which oscillates readily without any cooperative effects.Comment: 15 pages, 8 figures. Accepted by the HFSP journal (13/09/07

Assessing Random Dynamical Network Architectures for Nanoelectronics

Independent of the technology, it is generally expected that future nanoscale devices will be built from vast numbers of densely arranged devices that exhibit high failure rates. Other than that, there is little consensus on what type of technology and computing architecture holds most promises to go far beyond today's top-down engineered silicon devices. Cellular automata (CA) have been proposed in the past as a possible class of architectures to the von Neumann computing architecture, which is not generally well suited for future parallel and fine-grained nanoscale electronics. While the top-down engineered semi-conducting technology favors regular and locally interconnected structures, future bottom-up self-assembled devices tend to have irregular structures because of the current lack precise control over these processes. In this paper, we will assess random dynamical networks, namely Random Boolean Networks (RBNs) and Random Threshold Networks (RTNs), as alternative computing architectures and models for future information processing devices. We will illustrate that--from a theoretical perspective--they offer superior properties over classical CA-based architectures, such as inherent robustness as the system scales up, more efficient information processing capabilities, and manufacturing benefits for bottom-up designed devices, which motivates this investigation. We will present recent results on the dynamic behavior and robustness of such random dynamical networks while also including manufacturing issues in the assessment.Comment: 8 pages, 6 figures, IEEE/ACM Symposium on Nanoscale Architectures, NANOARCH 2008, Anaheim, CA, USA, Jun 12-13, 200