Dataset Information

A novel computational framework for simultaneous integration of multiple types of genomic data to identify microRNA-gene regulatory modules.

ABSTRACT:

Motivation

It is well known that microRNAs (miRNAs) and genes work cooperatively to form the key part of gene regulatory networks. However, the specific functional roles of most miRNAs and their combinatorial effects in cellular processes are still unclear. The availability of multiple types of functional genomic data provides unprecedented opportunities to study the miRNA-gene regulation. A major challenge is how to integrate the diverse genomic data to identify the regulatory modules of miRNAs and genes.

Results

Here we propose an effective data integration framework to identify the miRNA-gene regulatory comodules. The miRNA and gene expression profiles are jointly analyzed in a multiple non-negative matrix factorization framework, and additional network data are simultaneously integrated in a regularized manner. Meanwhile, we employ the sparsity penalties to the variables to achieve modular solutions. The mathematical formulation can be effectively solved by an iterative multiplicative updating algorithm. We apply the proposed method to integrate a set of heterogeneous data sources including the expression profiles of miRNAs and genes on 385 human ovarian cancer samples, computationally predicted miRNA-gene interactions, and gene-gene interactions. We demonstrate that the miRNAs and genes in 69% of the regulatory comodules are significantly associated. Moreover, the comodules are significantly enriched in known functional sets such as miRNA clusters, GO biological processes and KEGG pathways, respectively. Furthermore, many miRNAs and genes in the comodules are related with various cancers including ovarian cancer. Finally, we show that comodules can stratify patients (samples) into groups with significant clinical characteristics.

Availability

The program and supplementary materials are available at http://zhoulab.usc.edu/SNMNMF/.

Contact

xjzhou@usc.edu; zsh@amss.ac.cn

SUBMITTER: Zhang S

PROVIDER: S-EPMC3117336 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Publications

A novel computational framework for simultaneous integration of multiple types of genomic data to identify microRNA-gene regulatory modules.

Zhang Shihua S Li Qingjiao Q Liu Juan J Zhou Xianghong Jasmine XJ

Bioinformatics (Oxford, England) 20110701 13

<h4>Motivation</h4>It is well known that microRNAs (miRNAs) and genes work cooperatively to form the key part of gene regulatory networks. However, the specific functional roles of most miRNAs and their combinatorial effects in cellular processes are still unclear. The availability of multiple types of functional genomic data provides unprecedented opportunities to study the miRNA-gene regulation. A major challenge is how to integrate the diverse genomic data to identify the regulatory modules o ...[more]

PMID: 21685098

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Project description:BackgroundHigh throughput data are complex and methods that reveal structure underlying the data are most useful. Principal component analysis, frequently implemented as a singular value decomposition, is a popular technique in this respect. Nowadays often the challenge is to reveal structure in several sources of information (e.g., transcriptomics, proteomics) that are available for the same biological entities under study. Simultaneous component methods are most promising in this respect. However, the interpretation of the principal and simultaneous components is often daunting because contributions of each of the biomolecules (transcripts, proteins) have to be taken into account.ResultsWe propose a sparse simultaneous component method that makes many of the parameters redundant by shrinking them to zero. It includes principal component analysis, sparse principal component analysis, and ordinary simultaneous component analysis as special cases. Several penalties can be tuned that account in different ways for the block structure present in the integrated data. This yields known sparse approaches as the lasso, the ridge penalty, the elastic net, the group lasso, sparse group lasso, and elitist lasso. In addition, the algorithmic results can be easily transposed to the context of regression. Metabolomics data obtained with two measurement platforms for the same set of Escherichia coli samples are used to illustrate the proposed methodology and the properties of different penalties with respect to sparseness across and within data blocks.ConclusionSparse simultaneous component analysis is a useful method for data integration: First, simultaneous analyses of multiple blocks offer advantages over sequential and separate analyses and second, interpretation of the results is highly facilitated by their sparseness. The approach offered is flexible and allows to take the block structure in different ways into account. As such, structures can be found that are exclusively tied to one data platform (group lasso approach) as well as structures that involve all data platforms (Elitist lasso approach).AvailabilityThe additional file contains a MATLAB implementation of the sparse simultaneous component method.

Dataset Information

A novel computational framework for simultaneous integration of multiple types of genomic data to identify microRNA-gene regulatory modules.

Motivation

Results

Availability

Contact

Publications

A novel computational framework for simultaneous integration of multiple types of genomic data to identify microRNA-gene regulatory modules.

Similar Datasets

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