Dataset Information

Sparse multivariate factor analysis regression models and its applications to integrative genomics analysis.

ABSTRACT: The multivariate regression model is a useful tool to explore complex associations between two kinds of molecular markers, which enables the understanding of the biological pathways underlying disease etiology. For a set of correlated response variables, accounting for such dependency can increase statistical power. Motivated by integrative genomic data analyses, we propose a new methodology-sparse multivariate factor analysis regression model (smFARM), in which correlations of response variables are assumed to follow a factor analysis model with latent factors. This proposed method not only allows us to address the challenge that the number of association parameters is larger than the sample size, but also to adjust for unobserved genetic and/or nongenetic factors that potentially conceal the underlying response-predictor associations. The proposed smFARM is implemented by the EM algorithm and the blockwise coordinate descent algorithm. The proposed methodology is evaluated and compared to the existing methods through extensive simulation studies. Our results show that accounting for latent factors through the proposed smFARM can improve sensitivity of signal detection and accuracy of sparse association map estimation. We illustrate smFARM by two integrative genomics analysis examples, a breast cancer dataset, and an ovarian cancer dataset, to assess the relationship between DNA copy numbers and gene expression arrays to understand genetic regulatory patterns relevant to the disease. We identify two trans-hub regions: one in cytoband 17q12 whose amplification influences the RNA expression levels of important breast cancer genes, and the other in cytoband 9q21.32-33, which is associated with chemoresistance in ovarian cancer.

SUBMITTER: Zhou Y

PROVIDER: S-EPMC5154917 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Sparse multivariate factor analysis regression models and its applications to integrative genomics analysis.

Zhou Yan Y Wang Pei P Wang Xianlong X Zhu Ji J Song Peter X-K PX

Genetic epidemiology 20161110 1

The multivariate regression model is a useful tool to explore complex associations between two kinds of molecular markers, which enables the understanding of the biological pathways underlying disease etiology. For a set of correlated response variables, accounting for such dependency can increase statistical power. Motivated by integrative genomic data analyses, we propose a new methodology-sparse multivariate factor analysis regression model (smFARM), in which correlations of response variable ...[more]

PMID: 27862229

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Project description:A variety of high throughput genome-wide assays enable the exploration of genetic risk factors underlying complex traits. Although these studies have remarkable impact on identifying susceptible biomarkers, they suffer from issues such as limited sample size and low reproducibility. Combining individual studies of different genetic levels/platforms has the promise to improve the power and consistency of biomarker identification. In this paper, we propose a novel integrative method, namely sparse group multitask regression, for integrating diverse omics datasets, platforms, and populations to identify risk genes/factors of complex diseases. This method combines multitask learning with sparse group regularization, which will: (1) treat the biomarker identification in each single study as a task and then combine them by multitask learning; (2) group variables from all studies for identifying significant genes; (3) enforce sparse constraint on groups of variables to overcome the "small sample, but large variables" problem. We introduce two sparse group penalties: sparse group lasso and sparse group ridge in our multitask model, and provide an effective algorithm for each model. In addition, we propose a significance test for the identification of potential risk genes. Two simulation studies are performed to evaluate the performance of our integrative method by comparing it with conventional meta-analysis method. The results show that our sparse group multitask method outperforms meta-analysis method significantly. In an application to our osteoporosis studies, 7 genes are identified as significant genes by our method and are found to have significant effects in other three independent studies for validation. The most significant gene SOD2 has been identified in our previous osteoporosis study involving the same expression dataset. Several other genes such as TREML2, HTR1E, and GLO1 are shown to be novel susceptible genes for osteoporosis, as confirmed from other studies.

Dataset Information

Sparse multivariate factor analysis regression models and its applications to integrative genomics analysis.

Publications

Sparse multivariate factor analysis regression models and its applications to integrative genomics analysis.

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