Mihaela T. Matache

Dynamics of asynchronous random Boolean networks with asynchrony generated by stochastic processes.

An asynchronous Boolean network with N nodes whose states at each time point are determined by certain parent nodes is considered. We make use of the models developed by Matache and Heidel [Matache, M.T., Heidel, J., 2005. Asynchronous random Boolean network model based on elementary cellular automata rule 126. Phys. Rev. E 71, 026232] for a constant number of parents, and Matache [Matache, M.T., 2006. Asynchronous random Boolean network model with variable number of parents based on elementary cellular automata rule 126. IJMPB 20 (8), 897-923] for a varying number of parents. In both these papers the authors consider an asynchronous updating of all nodes, with asynchrony generated by various random distributions. We supplement those results by using various stochastic processes as generators for the number of nodes to be updated at each time point. In this paper we use the following stochastic processes: Poisson process, random walk, birth and death process, Brownian motion, and fractional Brownian motion. We study the dynamics of the model through sensitivity of the orbits to initial values, bifurcation diagrams, and fixed-point analysis. The dynamics of the system show that the number of nodes to be updated at each time point is of great importance, especially for the random walk, the birth and death, and the Brownian motion processes. Small or moderate values for the number of updated nodes generate order, while large values may generate chaos depending on the underlying parameters. The Poisson process generates order. With fractional Brownian motion, as the values of the Hurst parameter increase, the system exhibits order for a wider range of combinations of the underlying parameters.

Mean-field Boolean network model of a signal transduction network

In this paper we provide a mean-field Boolean network model for a signal transduction network of a generic fibroblast cell. The network consists of several main signaling pathways, including the receptor tyrosine kinase, the G-protein coupled receptor, and the Integrin signaling pathway. The network consists of 130 nodes, each representing a signaling molecule (mainly proteins). Nodes are governed by Boolean dynamics including canalizing functions as well as totalistic Boolean functions that depend only on the overall fraction of active nodes. We categorize the Boolean functions into several different classes. Using a mean-field approach we generate a mathematical formula for the probability of a node becoming active at any time step. The model is shown to be a good match for the actual network. This is done by iterating both the actual network and the model and comparing the results numerically. Using the Boolean model it is shown that the system is stable under a variety of parameter combinations. It is also shown that this model is suitable for assessing the dynamics of the network under protein mutations. Analytical results support the numerical observations that in the long-run at most half of the nodes of the network are active.

Clinical experience and examination performance: is there a correlation?

Context  The Liaison Committee on Medical Education (LCME) requires there to be: ‘…comparable educational experiences and equivalent methods of evaluation across all alternative instructional sites within a given discipline’. It is an LCME accreditation requirement that students encounter similar numbers of patients with similar diagnoses. However, previous empirical studies have not shown a correlation between the numbers of patients seen by students and performance on multiple‐choice examinations.

Sensitivity analysis of biological Boolean networks using information fusion based on nonadditive set functions.

BackgroundAn algebraic method for information fusion based on nonadditive set functions is used to assess the joint contribution of Boolean network attributes to the sensitivity of the network to individual node mutations. The node attributes or characteristics under consideration are: in-degree, out-degree, minimum and average path lengths, bias, average sensitivity of Boolean functions, and canalizing degrees. The impact of node mutations is assessed using as target measure the average Hamming distance between a non-mutated/wild-type network and a mutated network.ResultsWe find that for a biochemical signal transduction network consisting of several main signaling pathways whose nodes represent signaling molecules (mainly proteins), the algebraic method provides a robust classification of attribute contributions. This method indicates that for the biochemical network, the most significant impact is generated mainly by the combined effects of two attributes: out-degree, and average sensitivity of nodes.ConclusionsThe results support the idea that both topological and dynamical properties of the nodes need to be under consideration. The algebraic method is robust against the choice of initial conditions and partition of data sets in training and testing sets for estimation of the nonadditive set functions of the information fusion procedure.

Operator self-similar processes on Banach spaces

Operator self-similar (OSS) stochastic processes on arbitrary Banach spaces are considered. If the family of expectations of such a process is a spanning subset of the space, it is proved that the scaling family of operators of the process under consideration is a uniquely determined multiplicative group of operators. If the expectation-function of the process is continuous, it is proved that the expectations of the process have power-growth with exponent greater than or equal to 0, that is, their norm is less than a nonnegative constant times such a power-function, provided that the linear space spanned by the expectations has category 2 (in the sense of Baire) in its closure. It is shown that OSS processes whose expectation-function is differentiable on an interval (s0,∞), for some s0≥1, have a unique scaling family of operators of the form {sH:s>0}, if the expectations of the process span a dense linear subspace of category 2. The existence of a scaling family of the form {sH:s>0} is proved for proper Hilbert space OSS processes with an Abelian scaling family of positive operators.

Hilbert Spaces Induced by Toeplitz Covariance Kernels

We consider the reproducing kernel Hilbert space H μ induced by a kernel which is obtained using the Fourier-Stieltjes transform of a regular, positive, finite Borel measure μ on a locally compact abelian topological group Γ. Denote by G the dual of Γ. We determine H μ as a certain subspace of the space C o(G) of all continuous function on G vanishing at infinity. Our main application is calculating the reproducing kernel Hilbert spaces induced by the Toeplitz covariance kernels of some well-known stochastic processes.

On the sensitivity to noise of a Boolean function

In this paper we generate upper and lower bounds for the sensitivity to noise of a Boolean function using relaxed assumptions on input choices and noise. The robustness of a Boolean network to noisy inputs is related to the average sensitivity of that function. The average sensitivity measures how sensitive to changes in the inputs the output of the function is. The average sensitivity of Boolean functions can indicate whether a specific random Boolean network constructed from those functions is ordered, chaotic, or in critical phase. We give an exact formula relating the sensitivity to noise and the average sensitivity of a Boolean function. The analytic approach is supplemented by numerical results that illustrate the overall behavior of the sensitivities as various Boolean functions are considered. It is observed that, for certain parameter combinations, the upper estimates in this paper are sharper than other estimates in the literature and that the lower estimates are very close to the actual values ...

Logical Reduction of Biological Networks to Their Most Determinative Components.

Boolean networks have been widely used as models for gene regulatory networks, signal transduction networks, or neural networks, among many others. One of the main difficulties in analyzing the dynamics of a Boolean network and its sensitivity to perturbations or mutations is the fact that it grows exponentially with the number of nodes. Therefore, various approaches for simplifying the computations and reducing the network to a subset of relevant nodes have been proposed in the past few years. We consider a recently introduced method for reducing a Boolean network to its most determinative nodes that yield the highest information gain. The determinative power of a node is obtained by a summation of all mutual information quantities over all nodes having the chosen node as a common input, thus representing a measure of information gain obtained by the knowledge of the node under consideration. The determinative power of nodes has been considered in the literature under the assumption that the inputs are independent in which case one can use the Bahadur orthonormal basis. In this article, we relax that assumption and use a standard orthonormal basis instead. We use techniques of Hilbert space operators and harmonic analysis to generate formulas for the sensitivity to perturbations of nodes, quantified by the notions of influence, average sensitivity, and strength. Since we work on finite-dimensional spaces, our formulas and estimates can be and are formulated in plain matrix algebra terminology. We analyze the determinative power of nodes for a Boolean model of a signal transduction network of a generic fibroblast cell. We also show the similarities and differences induced by the alternative complete orthonormal basis used. Among the similarities, we mention the fact that the knowledge of the states of the most determinative nodes reduces the entropy or uncertainty of the overall network significantly. In a special case, we obtain a stronger result than in previous works, showing that a large information gain from a set of input nodes generates increased sensitivity to perturbations of those inputs.

QUEUEING SYSTEMS FOR MULTIPLE FBM-BASED TRAFFIC MODELS

A multiple fractional Brownian motion (FBM)-based traffic model is considered. Various lower bounds for the overflow probability of the associated queueing system are obtained. Based on a probabilistic bound for the busy period of an ATM queueing system associated with a multiple FBM-based input traffic, a minimal dynamic buffer allocation function (DBAF) is obtained and a DBAF-allocation algorithm is designed. The purpose is to create an upper bound for the queueing system associated with the traffic. This upper bound, called a DBAF, is a function of time, dynamically bouncing with the traffic. An envelope process associated with the multiple FBM-based traffic model is introduced and used to estimate the queue size of the queueing system associated with that traffic model.

Identification of Biologically Essential Nodes via Determinative Power in Logical Models of Cellular Processes

A variety of biological networks can be modeled as logical or Boolean networks. However, a simplification of the reality to binary states of the nodes does not ease the difficulty of analyzing the dynamics of large, complex networks, such as signal transduction networks, due to the exponential dependence of the state space on the number of nodes. This paper considers a recently introduced method for finding a fairly small subnetwork, representing a collection of nodes that determine the states of most other nodes with a reasonable level of entropy. The subnetwork contains the most determinative nodes that yield the highest information gain. One of the goals of this paper is to propose an algorithm for finding a suitable subnetwork size. The information gain is quantified by the so-called determinative power of the nodes, which is obtained via the mutual information, a concept originating in information theory. We find the most determinative nodes for 36 network models available in the online database Cell Collective (http://cellcollective.org). We provide statistical information that indicates a weak correlation between the subnetwork size and other variables, such as network size, or maximum and average determinative power of nodes. We observe that the proportion represented by the subnetwork in comparison to the whole network shows a weak tendency to decrease for larger networks. The determinative power of nodes is weakly correlated to the number of outputs of a node, and it appears to be independent of other topological measures such as closeness or betweenness centrality. Once the subnetwork of the most determinative nodes is identified, we generate a biological function analysis of its nodes for some of the 36 networks. The analysis shows that a large fraction of the most determinative nodes are essential and involved in crucial biological functions. The biological pathway analysis of the most determinative nodes shows that they are involved in important disease pathways.