Dataset Information

Identification of significant genes in genomics using Bayesian variable selection methods.

ABSTRACT: In the studies of genomics, it is essential to select a small number of genes that are more significant than the others for research ranging from candidate gene studies to genome-wide association studies. In this study, we proposed a Bayesian method for identifying the promising candidate genes that are significantly more influential than the others. We employed the framework of variable selection and a Gibbs sampling based technique to identify significant genes. The proposed approach was applied to a genomics study for persons with chronic fatigue syndrome. Our studies show that the proposed Bayesian methodology is effective for deriving models for genomic studies and for providing information on significant genes.

SUBMITTER: Lin E

PROVIDER: S-EPMC3169938 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

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Identification of significant genes in genomics using Bayesian variable selection methods.

Lin Eugene E Huang Lung-Cheng LC

Advances and applications in bioinformatics and chemistry : AABC 20080701

In the studies of genomics, it is essential to select a small number of genes that are more significant than the others for research ranging from candidate gene studies to genome-wide association studies. In this study, we proposed a Bayesian method for identifying the promising candidate genes that are significantly more influential than the others. We employed the framework of variable selection and a Gibbs sampling based technique to identify significant genes. The proposed approach was appli ...[more]

PMID: 21918603

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Project description:Significant advances in biotechnology have allowed for simultaneous measurement of molecular data across multiple genomic, epigenomic and transcriptomic levels from a single tumor/patient sample. This has motivated systematic data-driven approaches to integrate multi-dimensional structured datasets, since cancer development and progression is driven by numerous co-ordinated molecular alterations and the interactions between them. We propose a novel multi-scale Bayesian approach that combines integrative graphical structure learning from multiple sources of data with a variable selection framework-to determine the key genomic drivers of cancer progression. The integrative structure learning is first accomplished through novel joint graphical models for heterogeneous (mixed scale) data, allowing for flexible and interpretable incorporation of prior existing knowledge. This subsequently informs a variable selection step to identify groups of co-ordinated molecular features within and across platforms associated with clinical outcomes of cancer progression, while according appropriate adjustments for multicollinearity and multiplicities. We evaluate our methods through rigorous simulations to establish superiority over existing methods that do not take the network and/or prior information into account. Our methods are motivated by and applied to a glioblastoma multiforme (GBM) dataset from The Cancer Genome Atlas to predict patient survival times integrating gene expression, copy number and methylation data. We find a high concordance between our selected prognostic gene network modules with known associations with GBM. In addition, our model discovers several novel cross-platform network interactions (both cis and trans acting) between gene expression, copy number variation associated gene dosing and epigenetic regulation through promoter methylation, some with known implications in the etiology of GBM. Our framework provides a useful tool for biomedical researchers, since clinical prediction using multi-platform genomic information is an important step towards personalized treatment of many cancers.

Dataset Information

Identification of significant genes in genomics using Bayesian variable selection methods.

Publications

Identification of significant genes in genomics using Bayesian variable selection methods.

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