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Modeling and analyzing gene co-expression in hepatocellular carcinoma using actor-semiotic networks and centrality signatures.

ABSTRACT: Primary hepatocellular carcinoma (HCC) is currently the fifth most common malignancy and the third most common cause of cancer mortality worldwide. Because of its high prevalence in developing nations, there have been numerous efforts made in the molecular characterization of primary HCC. However, a better understanding into the pathology of HCC required software-assisted network modeling and analysis. In this paper, the author presented his first attempt in exploring the biological implication of gene co-expression in HCC using actor-semiotic network modeling and analysis. The network was first constructed by integrating inter-actor relationships, e.g. gene co-expression, microRNA-to-gene, and protein interactions, with semiotic relationships, e.g. gene-to-Gene Ontology Process. Topological features that are highly discriminative of the HCC phenotype were identified by visual inspection. Finally, the author devised a graph signature-based analysis method to supplement the network exploration.

SUBMITTER: Fung DC

PROVIDER: S-EPMC2623292 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

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Modeling and analyzing gene co-expression in hepatocellular carcinoma using actor-semiotic networks and centrality signatures.

Fung David C Y DC

Cancer informatics 20081105

Primary hepatocellular carcinoma (HCC) is currently the fifth most common malignancy and the third most common cause of cancer mortality worldwide. Because of its high prevalence in developing nations, there have been numerous efforts made in the molecular characterization of primary HCC. However, a better understanding into the pathology of HCC required software-assisted network modeling and analysis. In this paper, the author presented his first attempt in exploring the biological implication ...[more]

PMID: 19259423

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Project description:BackgroundCurrent microRNA (miRNA) research in progress has engendered rapid accumulation of expression data evolving from microarray experiments. Such experiments are generally performed over different tissues belonging to a specific species of metazoan. For disease diagnosis, microarray probes are also prepared with tissues taken from similar organs of different candidates of an organism. Expression data of miRNAs are frequently mapped to co-expression networks to study the functions of miRNAs, their regulation on genes and to explore the complex regulatory network that might exist between Transcription Factors (TFs), genes and miRNAs. These directions of research relating miRNAs are still not fully explored, and therefore, construction of reliable and compatible methods for mining miRNA co-expression networks has become an emerging area. This paper introduces a novel method for mining the miRNA co-expression networks in order to obtain co-expressed miRNAs under the hypothesis that these might be regulated by common TFs.ResultsThree co-expression networks, configured from one patient-specific, one tissue-specific and a stem cell-based miRNA expression data, are studied for analyzing the proposed methodology. A novel compactness measure is introduced. The results establish the statistical significance of the sets of miRNAs evolved and the efficacy of the self-pruning phase employed by the proposed method. All these datasets yield similar network patterns and produce coherent groups of miRNAs. The existence of common TFs, regulating these groups of miRNAs, is empirically tested. The results found are very promising. A novel visual validation method is also proposed that reflects the homogeneity as well as statistical properties of the grouped miRNAs. This visual validation method provides a promising and statistically significant graphical tool for expression analysis.ConclusionA heuristic mining methodology that resembles a clustering motivation is proposed in this paper. However, there remains a basic difference between the mining method and a clustering approach. The heuristic approach can produce priority modules (PM) from an miRNA co-expression network, by employing a self-pruning phase, which are analyzed for statistical and biological significance. The mining algorithm minimizes the space/time complexity of the analysis, and also handles noise in the data. In addition, the mining method reveals promising results in the unsupervised analysis of TF-miRNA regulation.

Dataset Information

Modeling and analyzing gene co-expression in hepatocellular carcinoma using actor-semiotic networks and centrality signatures.

Publications

Modeling and analyzing gene co-expression in hepatocellular carcinoma using actor-semiotic networks and centrality signatures.

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