A swarm intelligence based scheme for reduction of false positives in inferred gene regulatory networks

A Simple Approach for Representation of Gene Regulatory Networks (GRN)

Abstract: Gene expressions are controlled by a series of processes known as Gene Regulation, and their abstract mapping is represented by Gene Regulatory Network (GRN) which is a descriptive model of gene interactions. Reverse engineering GRNs can reveal the complexity of gene interactions whose comprehension can lead to several other details. RNA-seq data provides better measurement of gene expressions, however it is difficult to infer GRNs using it because of its discreteness. Multiple other methods have already been proposed to infer GRN using RNA-seq data, but these methodologies are difficult to grasp. In this paper, a simple model is presented to infer GRNs, using RNA-seq based coexpression map provided by GeneFriends database, and a graph-based database tool is used to create regulatory network. The obtained results show that it is convenient to use graph database tools to work with regulatory networks instead of developing a new model from scratch.

Wisdom of crowds for robust gene network inference

Abstract: Reconstructing gene regulatory networks from high-throughput data is a long-standing challenge. Through the Dialogue on Reverse Engineering Assessment and Methods (DREAM) project, we performed a comprehensive blind assessment of over 30 network inference methods on Escherichia coli, Staphylococcus aureus, Saccharomyces cerevisiae and in silico microarray data. We characterize the performance, data requirements and inherent biases of different inference approaches, and we provide guidelines for algorithm application and development. We observed that no single inference method performs optimally across all data sets. In contrast, integration of predictions from multiple inference methods shows robust and high performance across diverse data sets. We thereby constructed high-confidence networks for E. coli and S. aureus, each comprising ∼1,700 transcriptional interactions at a precision of ∼50%. We experimentally tested 53 previously unobserved regulatory interactions in E. coli, of which 23 (43%) were supported. Our results establish community-based methods as a powerful and robust tool for the inference of transcriptional gene regulatory networks.

Assigning numbers to the arrows: parameterizing a gene regulation network by using accurate expression kinetics.

Abstract: A basic challenge in systems biology is to understand the dynamical behavior of gene regulation networks. Current approaches aim at determining the network structure based on genomic-scale data. However, the network connectivity alone is not sufficient to define its dynamics; one needs to also specify the kinetic parameters for the regulation reactions. Here, we ask whether effective kinetic parameters can be assigned to a transcriptional network based on expression data. We present a combined experimental and theoretical approach based on accurate high temporal-resolution measurement of promoter activities from living cells by using green fluorescent protein (GFP) reporter plasmids. We present algorithms that use these data to assign effective kinetic parameters within a mathematical model of the network. To demonstrate this, we employ a well defined network, the SOS DNA repair system of Escherichia coli. We find a strikingly detailed temporal program of expression that correlates with the functional role of the SOS genes and is driven by a hierarchy of effective kinetic parameter strengths for the various promoters. The calculated parameters can be used to determine the kinetics of all SOS genes given the expression profile of just one representative, allowing a significant reduction in complexity. The concentration profile of the master SOS transcriptional repressor can be calculated, demonstrating that relative protein levels may be determined from purely transcriptional data. This finding opens the possibility of assigning kinetic parameters to transcriptional networks on a genomic scale.

GeneNetWeaver: in silico benchmark generation and performance profiling of network inference methods

Abstract: Motivation: Over the last decade, numerous methods have been developed for inference of regulatory networks from gene expression data. However, accurate and systematic evaluation of these methods is hampered by the difficulty of constructing adequate benchmarks and the lack of tools for a differentiated analysis of network predictions on such benchmarks. Results: Here, we describe a novel and comprehensive method for in silico benchmark generation and performance profiling of network inference methods available to the community as an open-source software called GeneNetWeaver (GNW). In addition to the generation of detailed dynamical models of gene regulatory networks to be used as benchmarks, GNW provides a network motif analysis that reveals systematic prediction errors, thereby indicating potential ways of improving inference methods. The accuracy of network inference methods is evaluated using standard metrics such as precision-recall and receiver operating characteristic curves. We show how GNW can be used to assess the performance and identify the strengths and weaknesses of six inference methods. Furthermore, we used GNW to provide the international Dialogue for Reverse Engineering Assessments and Methods (DREAM) competition with three network inference challenges (DREAM3, DREAM4 and DREAM5). Availability: GNW is available at http://gnw.sourceforge.net along with its Java source code, user manual and supporting data. Supplementary information: Supplementary data are available at Bioinformatics online.

Analyzing time series gene expression data

Abstract: Motivation: Time series expression experiments are an increasingly popular method for studying a wide range of biological systems. However, when analyzing these experiments researchers face many new computational challenges. Algorithms that are specifically designed for time series experiments are required so that we can take advantage of their unique features (such as the ability to infer causality from the temporal response pattern) and address the unique problems they raise (e.g. handling the different non-uniform sampling rates). Results: We present a comprehensive review of the current research in time series expression data analysis. We divide the computational challenges into four analysis levels: experimental design, data analysis, pattern recognition and networks. For each of these levels, we discuss computational and biological problems at that level and point out some of the methods that have been proposed to deal with these issues. Many open problems in all these levels are discussed. This review is intended to serve as both, a point of reference for experimental biologists looking for practical solutions for analyzing their data, and a starting point for computer scientists interested in working on the computational problems related to time series expression analysis.

Modeling transcriptional regulatory networks.

Abstract: Summary Developmental processes in complex animals are directed by a hardwired genomic regulatory code, the ultimate function of which is to set up a progression of transcriptional regulatory states in space and time. The code specifies the gene regulatory networks (GRNs) that underlie allmajor developmentalevents.Modelsof GRNs are required for analysis, for experimental manipulation and, most fundamentally, for comprehension of how GRNs work. To model GRNs requires knowledge of both their overall structure, which depends upon linkage amongst regulatory genes, and the modular building blocksofwhichGRNsareheirarchicallyconstructed.The building blocks consist of basic transcriptional control processes executed by one or a few functionally linked genes. We show how the functions of several such buildingblockscanbeconsideredinmathematicalterms, and discuss resolution of GRNs by both ‘‘top down’’ and ‘‘bottom up’’ approaches. BioEssays 24:1118–1129, 2002. 2002 Wiley Periodicals, Inc.