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Phenotype prediction by integrative network analysis of SNP and gene expression microarrays.

ABSTRACT: A long-term goal of biomedical research is to decipher how genetic processes influence disease formation. Ubiquitous and advancing microarray technology can measure millions of DNA structural variants (single-nucleotide polymorphisms, or SNPs) and thousands of gene transcripts (RNA expression microarrays) in cells. Both of these information modalities can be brought to bear on disease etiology. This paper develops a Bayesian network-based approach to integrate SNP and expression microarray data. The network models SNP-gene interactions using a phenotype-centric network. Inferring the network consists of two steps: variable selection and network learning. The learned network illustrates how functionally dependent SNPs and genes influence each other, and also serves as a predictor of the phenotype. The application of the proposed method to a pediatric acute lymphoblastic leukemia dataset demonstrates the feasibility of our approach and its impact on biological investigation and clinical practice.

SUBMITTER: Chang HH

PROVIDER: S-EPMC3343740 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Phenotype prediction by integrative network analysis of SNP and gene expression microarrays.

Chang Hsun-Hsien HH McGeachie Michael M

Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference 20110101

A long-term goal of biomedical research is to decipher how genetic processes influence disease formation. Ubiquitous and advancing microarray technology can measure millions of DNA structural variants (single-nucleotide polymorphisms, or SNPs) and thousands of gene transcripts (RNA expression microarrays) in cells. Both of these information modalities can be brought to bear on disease etiology. This paper develops a Bayesian network-based approach to integrate SNP and expression microarray data. ...[more]

PMID: 22255912

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Project description:BACKGROUND:Stratification of patient subpopulations that respond favorably to treatment or experience and adverse reaction is an essential step toward development of new personalized therapies and diagnostics. It is currently feasible to generate omic-scale biological measurements for all patients in a study, providing an opportunity for machine learning models to identify molecular markers for disease diagnosis and progression. However, the high variability of genetic background in human populations hampers the reproducibility of omic-scale markers. In this paper, we develop a biological network-based regularized artificial neural network model for prediction of phenotype from transcriptomic measurements in clinical trials. To improve model sparsity and the overall reproducibility of the model, we incorporate regularization for simultaneous shrinkage of gene sets based on active upstream regulatory mechanisms into the model. RESULTS:We benchmark our method against various regression, support vector machines and artificial neural network models and demonstrate the ability of our method in predicting the clinical outcomes using clinical trial data on acute rejection in kidney transplantation and response to Infliximab in ulcerative colitis. We show that integration of prior biological knowledge into the classification as developed in this paper, significantly improves the robustness and generalizability of predictions to independent datasets. We provide a Java code of our algorithm along with a parsed version of the STRING DB database. CONCLUSION:In summary, we present a method for prediction of clinical phenotypes using baseline genome-wide expression data that makes use of prior biological knowledge on gene-regulatory interactions in order to increase robustness and reproducibility of omic-scale markers. The integrated group-wise regularization methods increases the interpretability of biological signatures and gives stable performance estimates across independent test sets.

Dataset Information

Phenotype prediction by integrative network analysis of SNP and gene expression microarrays.

Publications

Phenotype prediction by integrative network analysis of SNP and gene expression microarrays.

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