AE-CTGAN: Autoencoder–Conditional Tabular GAN for Multi-Omics Imbalanced Class Handling and Cancer Outcome Prediction

The rapid advancement of sequencing technologies has led to the generation of complex multi-omics data, which are often high-dimensional, noisy, and imbalanced, posing significant challenges for traditional machine learning methods. The novelty of this work resides in the architecture-level integration of autoencoders with Generative Adversarial Network (GAN) and Conditional Tabular Generative Adversarial Network (CTGAN) models, where the autoencoder is employed for latent feature extraction and noise reduction, while GAN-based models are used for realistic sample generation and class imbalance mitigation in multi-omics cancer datasets. This study proposes a novel framework that combines an autoencoder for dimensionality reduction and a CTGAN for generating synthetic samples to balance underrepresented classes. The process starts with selecting the most discriminative features, then extracting latent representations for each omic type, merging them, and generating new minority samples. Finally, all samples are used to train a neural network to predict specific cancer outcomes, defined here as clinically relevant biomarkers or patient characteristics. In this work, the considered outcome in the bladder cancer is Tumor Mutational Burden (TMB), while the breast cancer outcome is menopausal status, a key factor in treatment planning. Experimental results show that the proposed model achieves high precision, with an average precision of 0.9929 for TMB prediction in bladder cancer and 0.9748 for menopausal status in breast cancer, and reaches perfect precision (1.000) for the positive class in both cases. In addition, the proposed AE–CTGAN framework consistently outperformed an autoencoder combined with a standard GAN across all evaluation metrics, achieving average accuracies of 0.9929 and 0.9748, recall values of 0.9846 and 0.9777, and F1-scores of 0.9922 for bladder and breast cancer datasets, respectively. A comparative fidelity analysis in the latent space further demonstrated the superiority of CTGAN, reducing the average Euclidean distance between real and synthetic samples by approximately 72% for bladder cancer and by up to 84% for breast cancer compared to a standard GAN. These findings confirm that CTGAN generates high-fidelity synthetic samples that preserve the structural characteristics of real multi-omics data, leading to more reliable class balancing and improved predictive performance. Overall, the proposed framework provides an effective and robust solution for handling class imbalance in multi-omics cancer data and enhances the accuracy of clinically relevant outcome prediction.