Singular Value Decomposition-Based Penalized Multinomial Regression for Classifying Imbalanced Medulloblastoma Subgroups Using Methylation Data

Medulloblastoma (MB) is a molecularly heterogeneous brain malignancy with large differences in clinical presentation. According to genomic studies, there are at least four distinct molecular subgroups of MB: sonic hedgehog (SHH), wingless/INT (WNT), Group 3, and Group 4. The treatment and outcomes depend on appropriate classification. It is difficult for the classification algorithms to identify these subgroups from an imbalanced MB genomic data set, where the distribution of samples among the MB subgroups may not be equal. To overcome this problem, we used singular value decomposition (SVD) and group lasso techniques to find DNA methylation probe features that maximize the separation between the different imbalanced MB subgroups. We used multinomial regression as a classification method to classify the four different molecular subgroups of MB using the reduced DNA methylation data. Coordinate descent is used to solve our loss function associated with the group lasso, which promotes sparsity. By using SVD, we were able to reduce the 321,174 probe features to just 200 features. Less than 40 features were successfully selected after applying the group lasso, which we then used as predictors for our classification models. Our proposed method achieved an average overall accuracy of 99% based on fivefold cross-validation technique. Our approach produces improved classification performance compared with the state-of-the-art methods for classifying MB molecular subgroups.