Robust Data Integration Method for Classification of Biomedical Data

We present a protocol for integrating two types of biological data - clinical and molecular - for more effective classification of patients with cancer. The proposed approach is a hybrid between early and late data integration strategy. In this hybrid protocol, the set of informative clinical features is extended by the classification results based on molecular data sets. The results are then treated as new synthetic variables. The hybrid protocol was applied to METABRIC breast cancer samples and TCGA urothelial bladder carcinoma samples. Various data types were used for clinical endpoint prediction: clinical data, gene expression, somatic copy number aberrations, RNA-Seq, methylation, and reverse phase protein array. The performance of the hybrid data integration was evaluated with a repeated cross validation procedure and compared with other methods of data integration: early integration and late integration via super learning. The hybrid method gave similar results to those obtained by the best of the tested variants of super learning. What is more, the hybrid method allowed for further sensitivity analysis and recursive feature elimination, which led to compact predictive models for cancer clinical endpoints. For breast cancer, the final model consists of eight clinical variables and two synthetic features obtained from molecular data. For urothelial bladder carcinoma, only two clinical features and one synthetic variable were necessary to build the best predictive model. We have shown that the inclusion of the synthetic variables based on the RNA expression levels and copy number alterations can lead to improved quality of prognostic tests. Thus, it should be considered for inclusion in wider medical practice.

Automated summary

A hybrid protocol integrating clinical and molecular data was proposed for more effective classification of cancer patients. This method yielded promising results in predicting clinical endpoints for breast cancer and urothelial bladder carcinoma samples.