Applying a GAN-based classifier to improve transcriptome-based prognostication in breast cancer

Abstract

Established prognostic tests based on limited numbers of transcripts can identify high-risk breast cancer patients, yet are approved only for individuals presenting with specific clinical features or disease characteristics. Deep learning algorithms could hold potential for stratifying patient cohorts based on full transcriptome data, yet the development of robust classifiers is hampered by the number of variables in omics datasets typically far exceeding the number of patients. To overcome this hurdle, we propose a classifier based on a data augmentation pipeline consisting of a Wasserstein generative adversarial network (GAN) with gradient penalty and an embedded auxiliary classifier to obtain a trained GAN discriminator (T-GAN-D). Applied to 1244 patients of the METABRIC breast cancer cohort, this classifier outperformed established breast cancer biomarkers in separating low- from high-risk patients (disease specific death, progression or relapse within 10 years from initial diagnosis). Importantly, the T-GAN-D also performed across independent, merged transcriptome datasets (METABRIC and TCGA-BRCA cohorts), and merging data improved overall patient stratification. In conclusion, the reiterative GAN-based training process allowed generating a robust classifier capable of stratifying low- vs high-risk patients based on full transcriptome data and across independent and heterogeneous breast cancer cohorts.