Uncovering the prognostic gene signatures for the improvement of risk stratification in cancers by using deep learning algorithm coupled with wavelet transform

Abstract

Background: The aim of gene expression-based clinical modelling in tumorigenesis is not only to accurately predict the clinical endpoints, but also to reveal the genome characteristics for downstream analysis for the purpose of understanding the mechanisms of cancers. Most of the conventional machine learning methods involved a gene filtering step, in which tens of thousands of genes were firstly filtered based on the gene expression levels by a statistical method with an arbitrary cutoff. Although gene filtering procedure helps to reduce the feature dimension and avoid overfitting, there is a risk that some pathogenic genes important to the disease will be ignored. Results: In this study, we proposed a novel deep learning approach by combining a convolutional neural network with stationary wavelet transform (SWT-CNN) for stratifying cancer patients and predicting their clinical outcomes without gene filtering based on tumor genomic profiles. The proposed SWT-CNN overperformed the state-of-art algorithms, including support vector machine (SVM) and logistic regression (LR), and produced comparable prediction performance to random forest (RF). Furthermore, for all the cancer types, we firstly proposed a method to weight the genes with the scores, which took advantage of the representative features in the hidden layer of convolutional neural network, and then selected the prognostic genes for the Cox proportional-hazards regression. The results showed that risk stratifications can be effectively improved by using the identified prognostic genes as feature, indicating that the representative features generated by SWT-CNN can well correlate the genes with prognostic risk in cancers and be helpful for selecting the prognostic gene signatures. Conclusions: Our results indicated that gene expression-based SWT-CNN model can be an excellent tool for stratifying the prognostic risk for cancer patients. In addition, the representative features of SWT-CNN were validated to be useful for evaluating the importance of the genes in the risk stratification and can be further used to identify the prognostic gene signatures.