An integrative deep learning framework for classifying molecular subtypes of breast cancer

摘要

Classification of breast cancer subtypes using multi-omics profiles is a difficult problem since the data sets are high-dimensional and highly correlated. Deep neural network (DNN) learning has demonstrated advantages over traditional methods as it does not require any hand-crafted features, but rather automatically extract features from raw data and efficiently analyze high-dimensional and correlated data. We aim to develop an integrative deep learning framework for classifying molecular subtypes of breast cancer. We collect copy number alteration and gene expression data measured on the same breast cancer patients from the Molecular Taxonomy of Breast Cancer International Consortium. We propose a deep learning model to integrate the omics datasets for predicting their molecular subtypes. The performance of our proposed DNN model is compared with some baseline models. Furthermore, we evaluate the misclassification of the subtypes using the learned deep features and explore their usefulness for clustering the breast cancer patients. We demonstrate that our proposed integrative deep learning model is superior to other deep learning and non-deep learning based models. Particularly, we get the best prediction result among the deep learning-based integration models when we integrate the two data sources using the concatenation layer in the models without sharing the weights. Using the learned deep features, we identify 6 breast cancer subgroups and show that Her2-enriched samples can be classified into more than one tumor subtype. Overall, the integrated model show better performance than those trained on individual data sources.