Detection of regulator genes and eQTLs in gene networks

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

An integrative top-down and bottom-up qualitative model construction framework for exploration of biochemical systems

The authors would like to thank the support on this research by the CRISP project (Combinatorial Responses In Stress Pathways) funded by the BBSRC (BB/F00513X/1) under the Systems Approaches to Biological Research (SABR) Initiative.Peer reviewedPublisher PD

Information visualization for DNA microarray data analysis: A critical review

Graphical representation may provide effective means of making sense of the complexity and sheer volume of data produced by DNA microarray experiments that monitor the expression patterns of thousands of genes simultaneously. The ability to use ldquoabstractrdquo graphical representation to draw attention to areas of interest, and more in-depth visualizations to answer focused questions, would enable biologists to move from a large amount of data to particular records they are interested in, and therefore, gain deeper insights in understanding the microarray experiment results. This paper starts by providing some background knowledge of microarray experiments, and then, explains how graphical representation can be applied in general to this problem domain, followed by exploring the role of visualization in gene expression data analysis. Having set the problem scene, the paper then examines various multivariate data visualization techniques that have been applied to microarray data analysis. These techniques are critically reviewed so that the strengths and weaknesses of each technique can be tabulated. Finally, several key problem areas as well as possible solutions to them are discussed as being a source for future work

Ecosystem-Oriented Distributed Evolutionary Computing

We create a novel optimisation technique inspired by natural ecosystems, where the optimisation works at two levels: a first optimisation, migration of genes which are distributed in a peer-to-peer network, operating continuously in time; this process feeds a second optimisation based on evolutionary computing that operates locally on single peers and is aimed at finding solutions to satisfy locally relevant constraints. We consider from the domain of computer science distributed evolutionary computing, with the relevant theory from the domain of theoretical biology, including the fields of evolutionary and ecological theory, the topological structure of ecosystems, and evolutionary processes within distributed environments. We then define ecosystem- oriented distributed evolutionary computing, imbibed with the properties of self-organisation, scalability and sustainability from natural ecosystems, including a novel form of distributed evolu- tionary computing. Finally, we conclude with a discussion of the apparent compromises resulting from the hybrid model created, such as the network topology.Comment: 8 pages, 5 figures. arXiv admin note: text overlap with arXiv:1112.0204, arXiv:0712.4159, arXiv:0712.4153, arXiv:0712.4102, arXiv:0910.067

Digital Ecosystems: Ecosystem-Oriented Architectures

We view Digital Ecosystems to be the digital counterparts of biological ecosystems. Here, we are concerned with the creation of these Digital Ecosystems, exploiting the self-organising properties of biological ecosystems to evolve high-level software applications. Therefore, we created the Digital Ecosystem, a novel optimisation technique inspired by biological ecosystems, where the optimisation works at two levels: a first optimisation, migration of agents which are distributed in a decentralised peer-to-peer network, operating continuously in time; this process feeds a second optimisation based on evolutionary computing that operates locally on single peers and is aimed at finding solutions to satisfy locally relevant constraints. The Digital Ecosystem was then measured experimentally through simulations, with measures originating from theoretical ecology, evaluating its likeness to biological ecosystems. This included its responsiveness to requests for applications from the user base, as a measure of the ecological succession (ecosystem maturity). Overall, we have advanced the understanding of Digital Ecosystems, creating Ecosystem-Oriented Architectures where the word ecosystem is more than just a metaphor.Comment: 39 pages, 26 figures, journa