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Identification of subtype specific miRNA-mRNA functional regulatory modules in matched miRNA-mRNA expression data: multiple myeloma as a case.

Zhang Y, Liu W, Xu Y, Li C, Wang Y, Yang H, Zhang C, Su F, Li Y, Li X - Biomed Res Int (2015)

Bottom Line: However, for heterogeneous diseases, the miRNA-mRNA regulatory mechanisms may differ between subtypes, leading to differences in clinical behavior.In this study, we integrated the Ping-Pong algorithm and multiobjective genetic algorithm to identify subtype specific miRNA-mRNA functional regulatory modules (MFRMs) through integrative analysis of three biological data sets: GO biological processes, miRNA target information, and matched miRNA and mRNA expression data.Furthermore, clustering analysis demonstrated that heterogeneous MFRMs were able to separate corresponding MM subtypes.

View Article: PubMed Central - PubMed

Affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, 194 Xuefu Road, Harbin 150081, China.

ABSTRACT
Identification of miRNA-mRNA modules is an important step to elucidate their combinatorial effect on the pathogenesis and mechanisms underlying complex diseases. Current identification methods primarily are based upon miRNA-target information and matched miRNA and mRNA expression profiles. However, for heterogeneous diseases, the miRNA-mRNA regulatory mechanisms may differ between subtypes, leading to differences in clinical behavior. In order to explore the pathogenesis of each subtype, it is important to identify subtype specific miRNA-mRNA modules. In this study, we integrated the Ping-Pong algorithm and multiobjective genetic algorithm to identify subtype specific miRNA-mRNA functional regulatory modules (MFRMs) through integrative analysis of three biological data sets: GO biological processes, miRNA target information, and matched miRNA and mRNA expression data. We applied our method on a heterogeneous disease, multiple myeloma (MM), to identify MM subtype specific MFRMs. The constructed miRNA-mRNA regulatory networks provide modular outlook at subtype specific miRNA-mRNA interactions. Furthermore, clustering analysis demonstrated that heterogeneous MFRMs were able to separate corresponding MM subtypes. These subtype specific MFRMs may aid in the further elucidation of the pathogenesis of each subtype and may serve to guide MM subtype diagnosis and treatment.

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Mentions: Let ENG×NC and RND×NC represent paired gene expression data matrix and miRNA expression data matrix, respectively. NG, ND, and NC represent the number of genes, miRNAs, and samples, respectively. Then the PPA is summarized in Pseudocode 1, where /x/, μ(x), and σ(x) denote the norm, mean, and standard deviation of the components xi in the vector x; ; tG, tD, and tC denote the threshold of genes, miRNAs, and samples, respectively; EG and EC represent the gene expression matrix normalized across genes and samples, respectively; RD and RC represent the miRNA expression matrix normalized across miRNAs and samples, respectively.


Identification of subtype specific miRNA-mRNA functional regulatory modules in matched miRNA-mRNA expression data: multiple myeloma as a case.

Zhang Y, Liu W, Xu Y, Li C, Wang Y, Yang H, Zhang C, Su F, Li Y, Li X - Biomed Res Int (2015)

© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4385567&req=5

Mentions: Let ENG×NC and RND×NC represent paired gene expression data matrix and miRNA expression data matrix, respectively. NG, ND, and NC represent the number of genes, miRNAs, and samples, respectively. Then the PPA is summarized in Pseudocode 1, where /x/, μ(x), and σ(x) denote the norm, mean, and standard deviation of the components xi in the vector x; ; tG, tD, and tC denote the threshold of genes, miRNAs, and samples, respectively; EG and EC represent the gene expression matrix normalized across genes and samples, respectively; RD and RC represent the miRNA expression matrix normalized across miRNAs and samples, respectively.

Bottom Line: However, for heterogeneous diseases, the miRNA-mRNA regulatory mechanisms may differ between subtypes, leading to differences in clinical behavior.In this study, we integrated the Ping-Pong algorithm and multiobjective genetic algorithm to identify subtype specific miRNA-mRNA functional regulatory modules (MFRMs) through integrative analysis of three biological data sets: GO biological processes, miRNA target information, and matched miRNA and mRNA expression data.Furthermore, clustering analysis demonstrated that heterogeneous MFRMs were able to separate corresponding MM subtypes.

View Article: PubMed Central - PubMed

Affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, 194 Xuefu Road, Harbin 150081, China.

ABSTRACT
Identification of miRNA-mRNA modules is an important step to elucidate their combinatorial effect on the pathogenesis and mechanisms underlying complex diseases. Current identification methods primarily are based upon miRNA-target information and matched miRNA and mRNA expression profiles. However, for heterogeneous diseases, the miRNA-mRNA regulatory mechanisms may differ between subtypes, leading to differences in clinical behavior. In order to explore the pathogenesis of each subtype, it is important to identify subtype specific miRNA-mRNA modules. In this study, we integrated the Ping-Pong algorithm and multiobjective genetic algorithm to identify subtype specific miRNA-mRNA functional regulatory modules (MFRMs) through integrative analysis of three biological data sets: GO biological processes, miRNA target information, and matched miRNA and mRNA expression data. We applied our method on a heterogeneous disease, multiple myeloma (MM), to identify MM subtype specific MFRMs. The constructed miRNA-mRNA regulatory networks provide modular outlook at subtype specific miRNA-mRNA interactions. Furthermore, clustering analysis demonstrated that heterogeneous MFRMs were able to separate corresponding MM subtypes. These subtype specific MFRMs may aid in the further elucidation of the pathogenesis of each subtype and may serve to guide MM subtype diagnosis and treatment.

Show MeSH
Related in: MedlinePlus