191,529 research outputs found

    Canalization and Symmetry in Boolean Models for Genetic Regulatory Networks

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    Canalization of genetic regulatory networks has been argued to be favored by evolutionary processes due to the stability that it can confer to phenotype expression. We explore whether a significant amount of canalization and partial canalization can arise in purely random networks in the absence of evolutionary pressures. We use a mapping of the Boolean functions in the Kauffman N-K model for genetic regulatory networks onto a k-dimensional Ising hypercube to show that the functions can be divided into different classes strictly due to geometrical constraints. The classes can be counted and their properties determined using results from group theory and isomer chemistry. We demonstrate that partially canalized functions completely dominate all possible Boolean functions, particularly for higher k. This indicates that partial canalization is extremely common, even in randomly chosen networks, and has implications for how much information can be obtained in experiments on native state genetic regulatory networks.Comment: 14 pages, 4 figures; version to appear in J. Phys.

    Network growth models and genetic regulatory networks

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    We study a class of growth algorithms for directed graphs that are candidate models for the evolution of genetic regulatory networks. The algorithms involve partial duplication of nodes and their links, together with innovation of new links, allowing for the possibility that input and output links from a newly created node may have different probabilities of survival. We find some counterintuitive trends as parameters are varied, including the broadening of indegree distribution when the probability for retaining input links is decreased. We also find that both the scaling of transcription factors with genome size and the measured degree distributions for genes in yeast can be reproduced by the growth algorithm if and only if a special seed is used to initiate the process.Comment: 8 pages with 7 eps figures; uses revtex4. Added references, cleaner figure

    Detection of regulator genes and eQTLs in gene networks

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    Genetic differences between individuals associated to quantitative phenotypic traits, including disease states, are usually found in non-coding genomic regions. These genetic variants are often also associated to differences in expression levels of nearby genes (they are "expression quantitative trait loci" or eQTLs for short) and presumably play a gene regulatory role, affecting the status of molecular networks of interacting genes, proteins and metabolites. Computational systems biology approaches to reconstruct causal gene networks from large-scale omics data have therefore become essential to understand the structure of networks controlled by eQTLs together with other regulatory genes, and to generate detailed hypotheses about the molecular mechanisms that lead from genotype to phenotype. Here we review the main analytical methods and softwares to identify eQTLs and their associated genes, to reconstruct co-expression networks and modules, to reconstruct causal Bayesian gene and module networks, and to validate predicted networks in silico.Comment: minor revision with typos corrected; review article; 24 pages, 2 figure

    Evolutionary robustness of differentiation in genetic regulatory networks

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    We investigate the ability of artificial Genetic Regulatory Networks (GRNs) to evolve differentiation. The proposed GRN model supports non-linear interaction between regulating factors, thereby facilitating the realization of complex regulatory logics. As a proof of concept we evolve GRNs of this kind to follow different pathways, producing two kinds of periodic dynamics in response to minimal differences in external input. Furthermore we find that successive increases in environmental pressure for differentiation, allowing a lineage to adapt gradually, compared to an immediate requirement for a switch between behaviors, yields better results on average. Apart from better success there is also less variability in performance, the latter indicating an increase in evolutionary robustness

    Parallel implementation of stochastic simulation for large-scale cellular processes

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    Experimental and theoretical studies have shown the importance of stochastic processes in genetic regulatory networks and cellular processes. Cellular networks and genetic circuits often involve small numbers of key proteins such as transcriptional factors and signaling proteins. In recent years stochastic models have been used successfully for studying noise in biological pathways, and stochastic modelling of biological systems has become a very important research field in computational biology. One of the challenge problems in this field is the reduction of the huge computing time in stochastic simulations. Based on the system of the mitogen-activated protein kinase cascade that is activated by epidermal growth factor, this work give a parallel implementation by using OpenMP and parallelism across the simulation. Special attention is paid to the independence of the generated random numbers in parallel computing, that is a key criterion for the success of stochastic simulations. Numerical results indicate that parallel computers can be used as an efficient tool for simulating the dynamics of large-scale genetic regulatory networks and cellular processes
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