Dataset Information

Construction of the influenza A virus infection-induced cell-specific inflammatory regulatory network based on mutual information and optimization.

ABSTRACT: BACKGROUND: Influenza A virus (IAV) infection-induced inflammatory regulatory networks (IRNs) are extremely complex and dynamic. Specific biological experiments for investigating the interactions between individual inflammatory factors cannot provide a detailed and insightful multidimensional view of IRNs. Recently, data from high-throughput technologies have permitted system-level analyses. The construction of large and cell-specific IRNs from high-throughput data is essential to understanding the pathogenesis of IAV infection. RESULTS: In this study, we proposed a computational method, which combines nonlinear ordinary differential equation (ODE)-based optimization with mutual information, to construct a cell-specific optimized IRN during IAV infection by integrating gene expression data with a prior knowledge of network topology. Moreover, we used the average relative error and sensitivity analysis to evaluate the effectiveness of our proposed approach. Furthermore, from the optimized IRN, we confirmed 45 interactions between proteins in biological experiments and identified 37 new regulatory interactions and 8 false positive interactions, including the following interactions: IL1? regulates TLR3, TLR3 regulates IFN-? and TNF regulates IL6. Most of these regulatory interactions are statistically significant by Z-statistic. The functional annotations of the optimized IRN demonstrated clearly that the defense response, immune response, response to wounding and regulation of cytokine production are the pivotal processes of IAV-induced inflammatory response. The pathway analysis results from the Kyoto Encyclopaedia of Genes and Genomes (KEGG) showed that 8 pathways are enriched significantly. The 5 pathways were validated by experiments, and 3 other pathways, including the intestinal immune network for IgA production, the cytosolic DNA-sensing pathway and the allograft rejection pathway, are the predicted novel pathways involved in the inflammatory response. CONCLUSIONS: Integration of knowledge-driven and data-driven methods allows us to construct an effective IRN during IAV infection. Based on the constructed network, we have identified new interactions among inflammatory factors and biological pathways. These findings provide new insight into our understanding of the molecular mechanisms in the inflammatory network in response to IAV infection. Further characterization and experimental validation of the interaction mechanisms identified from this study may lead to a novel therapeutic strategy for the control of infections and inflammatory responses.

SUBMITTER: Jin S

PROVIDER: S-EPMC4016583 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Construction of the influenza A virus infection-induced cell-specific inflammatory regulatory network based on mutual information and optimization.

Jin Suoqin S Zou Xiufen X

BMC systems biology 20131020

<h4>Background</h4>Influenza A virus (IAV) infection-induced inflammatory regulatory networks (IRNs) are extremely complex and dynamic. Specific biological experiments for investigating the interactions between individual inflammatory factors cannot provide a detailed and insightful multidimensional view of IRNs. Recently, data from high-throughput technologies have permitted system-level analyses. The construction of large and cell-specific IRNs from high-throughput data is essential to underst ...[more]

PMID: 24138989

Similar Datasets

Project description:UNLABELLED: BACKGROUND:Cancer therapy is a challenging research area because side effects often occur in chemo and radiation therapy. We intend to study a multi-targets and multi-components design that will provide synergistic results to improve efficiency of cancer therapy. METHODS:We have developed a general methodology, AMFES (Adaptive Multiple FEature Selection), for ranking and selecting important cancer biomarkers based on SVM (Support Vector Machine) classification. In particular, we exemplify this method by three datasets: a prostate cancer (three stages), a breast cancer (four subtypes), and another prostate cancer (normal vs. cancerous). Moreover, we have computed the target networks of these biomarkers as the signatures of the cancers with additional information (mutual information between biomarkers of the network). Then, we proposed a robust framework for synergistic therapy design approach which includes varies existing mechanisms. RESULTS:These methodologies were applied to three GEO datasets: GSE18655 (three prostate stages), GSE19536 (4 subtypes breast cancers) and GSE21036 (prostate cancer cells and normal cells) shown in. We selected 96 biomarkers for first prostate cancer dataset (three prostate stages), 72 for breast cancer (luminal A vs. luminal B), 68 for breast cancer (basal-like vs. normal-like), and 22 for another prostate cancer (cancerous vs. normal. In addition, we obtained statistically significant results of mutual information, which demonstrate that the dependencies among these biomarkers can be positive or negative. CONCLUSIONS:We proposed an efficient feature ranking and selection scheme, AMFES, to select an important subset from a large number of features for any cancer dataset. Thus, we obtained the signatures of these cancers by building their target networks. Finally, we proposed a robust framework of synergistic therapy for cancer patients. Our framework is not only supported by real GEO datasets but also aim to a multi-targets/multi-components drug design tool, which improves the traditional single target/single component analysis methods. This framework builds a computational foundation which can provide a clear classification of cancers and lead to an efficient cancer therapy.

Project description:The prediction of links among variables from a given dataset is a task referred to as network inference or reverse engineering. It is an open problem in bioinformatics and systems biology, as well as in other areas of science. Information theory, which uses concepts such as mutual information, provides a rigorous framework for addressing it. While a number of information-theoretic methods are already available, most of them focus on a particular type of problem, introducing assumptions that limit their generality. Furthermore, many of these methods lack a publicly available implementation. Here we present MIDER, a method for inferring network structures with information theoretic concepts. It consists of two steps: first, it provides a representation of the network in which the distance among nodes indicates their statistical closeness. Second, it refines the prediction of the existing links to distinguish between direct and indirect interactions and to assign directionality. The method accepts as input time-series data related to some quantitative features of the network nodes (such as e.g. concentrations, if the nodes are chemical species). It takes into account time delays between variables, and allows choosing among several definitions and normalizations of mutual information. It is general purpose: it may be applied to any type of network, cellular or otherwise. A Matlab implementation including source code and data is freely available (http://www.iim.csic.es/~gingproc/mider.html). The performance of MIDER has been evaluated on seven different benchmark problems that cover the main types of cellular networks, including metabolic, gene regulatory, and signaling. Comparisons with state of the art information-theoretic methods have demonstrated the competitive performance of MIDER, as well as its versatility. Its use does not demand any a priori knowledge from the user; the default settings and the adaptive nature of the method provide good results for a wide range of problems without requiring tuning.

Dataset Information

Construction of the influenza A virus infection-induced cell-specific inflammatory regulatory network based on mutual information and optimization.

Publications

Construction of the influenza A virus infection-induced cell-specific inflammatory regulatory network based on mutual information and optimization.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure