DegreeCox – a network-based regularization method for survival analysis
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- TL;DR
- We introduce DegreeCox, a method that uses biological networks to improve survival analysis models when analyzing high-dimensional genetic data.
- Problem
- In oncology, modeling patient survival data is challenging because the volume of available molecular information means that the number of features greatly exceeds the number of observations. While methods like LASSO help with interpretability, they often fail to fully exploit the relationships between features represented as graphs.
- Method
- We propose DegreeCox, a method that applies network-based regularizers to infer Cox proportional hazard models where features are genes and the outcome is patient survival, using network centrality measures to constrain the model.
- Results
- Tested on three ovarian cancer datasets using Gene Co-Expression Networks and Gene Functional Maps, DegreeCox improved the classification of high- and low-risk patients compared to RIDGE and LASSO, performing on par with NET-COX and yielding competitive RMSE and C-index results.
- Contributions
- Not specified in the abstract.
- Limitations
- Not specified in the abstract.
- Takeaways
- Network-based regularization is a promising approach for handling high-dimensional data, and the proposed centrality metrics can be extended to other topological properties of biological networks.
- Applications
- Not specified in the abstract.
- Topics
- Survival analysis, network-based regularization, Cox proportional hazard models, bioinformatics
- For industry
- Not specified in the abstract.
- Why it matters
- Not specified in the 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 propose DEGREECOX, 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 applied DEGREECOX 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 with RIDGE and LASSO, DEGREECOX shows an improvement in the classification of high and low risk patients in a par with NET-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.