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Identifying Gene Network Rewiring Using Robust Differential Graphical Model with Multivariate t-Distribution
Journal article

Identifying Gene Network Rewiring Using Robust Differential Graphical Model with Multivariate t-Distribution

Rui Yuan, Le Ou-Yang, Xiaohua Hu and Xiao-Fei Zhang
IEEE/ACM transactions on computational biology and bioinformatics, v 17(2), pp 712-718
01 Mar 2020
PMID: 30802872

Abstract

Biochemical Research Methods Biochemistry & Molecular Biology Computer Science Computer Science, Interdisciplinary Applications Life Sciences & Biomedicine Mathematics Mathematics, Interdisciplinary Applications Physical Sciences Science & Technology Statistics & Probability Technology
Identifying gene network rewiring under different biological conditions is important for understanding the mechanisms underlying complex diseases. Gaussian graphical models, which assume the data follow the multivariate normal distribution, are widely used to identify gene network rewiring. However, the normality assume often fails in reality since the data are contaminated by extreme outliers in general. In this study, we propose a new robust differential graphical model to identify gene network rewiring between two conditions based on the multivariate t-distribution. The multivariate t-distribution is more robust to outliers than the normal distribution since it has heavy tails and allows values far from the mean. A fused lasso penalty is used to borrow information across conditions to improve the results. We develop an expectation maximization algorithm to solve the optimization model. Experiment results on simulated data show that our method outperforms the state-of-the-art methods. Our method is also applied to identify gene network rewiring between luminal A and basal-like subtypes of breast cancer, and gene network rewiring between the proneural and mesenchymal subtypes of glioblastoma. Several key genes which drive gene network rewiring are discovered.

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Biochemical Research Methods
Computer Science, Interdisciplinary Applications
Mathematics, Interdisciplinary Applications
Statistics & Probability
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