Title
Differential Network Analysis via Weighted Fused Conditional Gaussian Graphical Model
Abstract
The development and prognosis of complex diseases usually involves changes in regulatory relationships among biomolecules. Understanding how the regulatory relationships change with genetic alterations can help to reveal the underlying biological mechanisms for complex diseases. Although several models have been proposed to estimate the differential network between two different states, they are not suitable to deal with situations where the molecules of interest are affected by other covariates. Nor can they make use of prior information that provides insights about the structures of biomolecular networks. In this study, we introduce a novel weighted fused conditional Gaussian graphical model to jointly estimate two state-specific biomolecular regulatory networks and their difference between two different states. Unlike previous differential network estimation methods, our model can take into account the related covariates and the prior network information when inferring differential networks. The effectiveness of our proposed model is first evaluated based on simulation studies. Experiment results demonstrate that our model outperforms other state-of-the-art differential networks estimation models in all cases. We then apply our model to identify the differential gene network between two subtypes of glioblastoma based on gene expression and miRNA expression data. Our model is able to discover known mechanisms of glioblastoma and provide interesting predictions.
Year
DOI
Venue
2020
10.1109/TCBB.2019.2924418
IEEE/ACM Transactions on Computational Biology and Bioinformatics
Keywords
DocType
Volume
Brain Neoplasms,Computational Biology,Computer Simulation,Gene Expression Profiling,Gene Regulatory Networks,Glioblastoma,Humans,Normal Distribution,Transcriptome
Journal
17
Issue
ISSN
Citations 
6
1545-5963
0
PageRank 
References 
Authors
0.34
0
4
Name
Order
Citations
PageRank
Le Ou-Yang16312.42
Xiao-Fei Zhang21089.43
Xiaohua Hu32819314.15
Hong Yan43628335.04