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

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. Several key genes which drive gene network rewiring are discovered.

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