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An effective method for network module extraction from microarray data.

ABSTRACT: BACKGROUND: The development of high-throughput Microarray technologies has provided various opportunities to systematically characterize diverse types of computational biological networks. Co-expression network have become popular in the analysis of microarray data, such as for detecting functional gene modules. RESULTS: This paper presents a method to build a co-expression network (CEN) and to detect network modules from the built network. We use an effective gene expression similarity measure called NMRS (Normalized mean residue similarity) to construct the CEN. We have tested our method on five publicly available benchmark microarray datasets. The network modules extracted by our algorithm have been biologically validated in terms of Q value and p value. CONCLUSIONS: Our results show that the technique is capable of detecting biologically significant network modules from the co-expression network. Biologist can use this technique to find groups of genes with similar functionality based on their expression information.

SUBMITTER: Mahanta P

PROVIDER: S-EPMC3426802 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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An effective method for network module extraction from microarray data.

Mahanta Priyakshi P Ahmed Hasin A HA Bhattacharyya Dhruba K DK Kalita Jugal K JK

BMC bioinformatics 20120824

<h4>Background</h4>The development of high-throughput Microarray technologies has provided various opportunities to systematically characterize diverse types of computational biological networks. Co-expression network have become popular in the analysis of microarray data, such as for detecting functional gene modules.<h4>Results</h4>This paper presents a method to build a co-expression network (CEN) and to detect network modules from the built network. We use an effective gene expression simila ...[more]

PMID: 23320896

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Project description:As humans age many suffer from a decrease in normal brain functions including spatial learning impairments. This study aimed to better understand the molecular mechanisms in age-associated spatial learning impairment (ASLI). We used a mathematical modeling approach implemented in Weighted Gene Co-expression Network Analysis (WGCNA) to create and compare gene network models of young (learning unimpaired) and aged (predominantly learning impaired) brains from a set of exploratory datasets in rats in the context of ASLI. The major goal was to overcome some of the limitations previously observed in the traditional meta- and pathway analysis using these data, and identify novel ASLI related genes and their networks based on co-expression relationship of genes. This analysis identified a set of network modules in the young, each of which is highly enriched with genes functioning in broad but distinct GO functional categories or biological pathways. Interestingly, the analysis pointed to a single module that was highly enriched with genes functioning in "learning and memory" related functions and pathways. Subsequent differential network analysis of this "learning and memory" module in the aged (predominantly learning impaired) rats compared to the young learning unimpaired rats allowed us to identify a set of novel ASLI candidate hub genes. Some of these genes show significant repeatability in networks generated from independent young and aged validation datasets. These hub genes are highly co-expressed with other genes in the network, which not only show differential expression but also differential co-expression and differential connectivity across age and learning impairment. The known function of these hub genes indicate that they play key roles in critical pathways, including kinase and phosphatase signaling, in functions related to various ion channels, and in maintaining neuronal integrity relating to synaptic plasticity and memory formation. Taken together, they provide a new insight and generate new hypotheses into the molecular mechanisms responsible for age associated learning impairment, including spatial learning.

Project description:BACKGROUND: In recent years, several authors have used probabilistic graphical models to learn expression modules and their regulatory programs from gene expression data. Despite the demonstrated success of such algorithms in uncovering biologically relevant regulatory relations, further developments in the area are hampered by a lack of tools to compare the performance of alternative module network learning strategies. Here, we demonstrate the use of the synthetic data generator SynTReN for the purpose of testing and comparing module network learning algorithms. We introduce a software package for learning module networks, called LeMoNe, which incorporates a novel strategy for learning regulatory programs. Novelties include the use of a bottom-up Bayesian hierarchical clustering to construct the regulatory programs, and the use of a conditional entropy measure to assign regulators to the regulation program nodes. Using SynTReN data, we test the performance of LeMoNe in a completely controlled situation and assess the effect of the methodological changes we made with respect to an existing software package, namely Genomica. Additionally, we assess the effect of various parameters, such as the size of the data set and the amount of noise, on the inference performance. RESULTS: Overall, application of Genomica and LeMoNe to simulated data sets gave comparable results. However, LeMoNe offers some advantages, one of them being that the learning process is considerably faster for larger data sets. Additionally, we show that the location of the regulators in the LeMoNe regulation programs and their conditional entropy may be used to prioritize regulators for functional validation, and that the combination of the bottom-up clustering strategy with the conditional entropy-based assignment of regulators improves the handling of missing or hidden regulators. CONCLUSION: We show that data simulators such as SynTReN are very well suited for the purpose of developing, testing and improving module network algorithms. We used SynTReN data to develop and test an alternative module network learning strategy, which is incorporated in the software package LeMoNe, and we provide evidence that this alternative strategy has several advantages with respect to existing methods.

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An effective method for network module extraction from microarray data.

Publications

An effective method for network module extraction from microarray data.

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