Dataset Information

Network-based genomic discovery: application and comparison of Markov random field models.

ABSTRACT: As biological knowledge accumulates rapidly, gene networks encoding genome-wide gene-gene interactions have been constructed. As an improvement over the standard mixture model that tests all the genes iid a priori, Wei and Li (2007) and Wei and Pan (2008) proposed modeling a gene network as a Discrete- or Gaussian-Markov random field (DMRF or GMRF) respectively in a mixture model to analyze genomic data. However, how these methods compare in practical applications in not well understood and this is the aim here. We also propose two novel constraints in prior specifications for the GMRF model and a fully Bayesian approach to the DMRF model. We assess the accuracy of estimating the False Discovery Rate (FDR) by posterior probabilities in the context of MRF models. Applications to a ChIP-chip data set and simulated data show that the modified GMRF models has superior performance as compared with other models, while both MRF-based mixture models, with reasonable robustness to misspecified gene networks, outperform the standard mixture model.

SUBMITTER: Wei P

PROVIDER: S-EPMC3046412 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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Publications

Network-based genomic discovery: application and comparison of Markov random field models.

Wei Peng P Pan Wei W

Journal of the Royal Statistical Society. Series C, Applied statistics 20100101 1

As biological knowledge accumulates rapidly, gene networks encoding genome-wide gene-gene interactions have been constructed. As an improvement over the standard mixture model that tests all the genes iid a priori, Wei and Li (2007) and Wei and Pan (2008) proposed modeling a gene network as a Discrete- or Gaussian-Markov random field (DMRF or GMRF) respectively in a mixture model to analyze genomic data. However, how these methods compare in practical applications in not well understood and this ...[more]

PMID: 21373371

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Project description:BACKGROUND:Recent advances in sequencing technologies have enabled parallel assays of chromatin accessibility and gene expression for major human cell lines. Such innovation provides a great opportunity to decode phenotypic consequences of genetic variation via the construction of predictive gene regulatory network models. However, there still lacks a computational method to systematically integrate chromatin accessibility information with gene expression data to recover complicated regulatory relationships between genes in a tissue-specific manner. RESULTS:We propose a Markov random field (MRF) model for constructing tissue-specific transcriptional regulatory networks via integrative analysis of DNase-seq and RNA-seq data. Our method, named CSNets (cell-line specific regulatory networks), first infers regulatory networks for individual cell lines using chromatin accessibility information, and then fine-tunes these networks using the MRF based on pairwise similarity between cell lines derived from gene expression data. Using this method, we constructed regulatory networks specific to 110 human cell lines and 13 major tissues with the use of ENCODE data. We demonstrated the high quality of these networks via comprehensive statistical analysis based on ChIP-seq profiles, functional annotations, taxonomic analysis, and literature surveys. We further applied these networks to analyze GWAS data of Crohn's disease and prostate cancer. Results were either consistent with the literature or provided biological insights into regulatory mechanisms of these two complex diseases. The website of CSNets is freely available at http://bioinfo.au.tsinghua.edu.cn/jianglab/CSNETS/ . CONCLUSIONS:CSNets demonstrated the power of joint analysis on epigenomic and transcriptomic data towards the accurate construction of gene regulatory network. Our work provides not only a useful resource of regulatory networks to the community, but also valuable experiences in methodology development for multi-omics data integration.

Dataset Information

Network-based genomic discovery: application and comparison of Markov random field models.

Publications

Network-based genomic discovery: application and comparison of Markov random field models.

Similar Datasets

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