DegreeCox – a network-based regularization method for survival analysis. Issue 16 (December 2016)

• Record Type: Journal Article
• Authors: Veríssimo, André; Oliveira, Arlindo Limede; Sagot, Marie-France; Vinga, Susana
• Is Part Of: BMC bioinformatics. Volume 17:Issue 16(2016)
• Page Start: 109
• Page End: 121
• Publication Date: 2016-12
• Subjects: Regularization -- Cox proportional models -- Network metrics; Bioinformatics -- Periodicals; Computational biology -- Periodicals; 570.285
• DOI: 10.1186/s12859-016-1310-4
• Languages: English
• ISSNs: 1471-2105

Abstract

Abstract Background Modeling survival oncological data has become a major challenge as the increase in the amount of molecular information nowadays available means that the number of features greatly exceeds the number of observations. One possible solution to cope with this dimensionality problem is the use of additional constraints in the cost function optimization.Lasso and other sparsity methods have thus already been successfully applied with such idea. Although this leads to more interpretable models, these methods still do not fully profit from the relations between the features, specially when these can be represented through graphs. We proposeDegreeCox, a method that applies network-based regularizers to infer Cox proportional hazard models, when the features are genes and the outcome is patient survival. In particular, we propose to use network centrality measures to constrain the model in terms of significant genes. Results We appliedDegreeCox to three datasets of ovarian cancer carcinoma and tested several centrality measures such as weighted degree, betweenness and closeness centrality. The a priori network information was retrieved from Gene Co-Expression Networks and Gene Functional Maps. When compared withRidge andLasso, DegreeCox shows an improvement in the classification of high and low risk patients in a par withNet-Cox . The use of network information is especially relevant with datasets that are not easily separated. In terms of RMSE and C-index, DegreeCox gives results that are similar to those of the best performing methods, in a few cases slightly better. Conclusions Network-based regularization seems a promising framework to deal with the dimensionality problem. The centrality metrics proposed can be easily expanded to accommodate other topological properties of different biological networks.