Identifying menopause-related breast cancer biomarkers is crucial for enhancing diagnosis, prognosis, and personalized treatment at that stage of the patient’s life. In this paper, we present a comprehensive framework for extracting multiomics biomarkers specifically related to breast cancer incidence before and after menopause. Our approach integrates DNA methylation, gene expression, and copy number alteration data using a systematic pipeline encompassing data preprocessing and handling class imbalance, dimensionality reduction, and classification. The framework starts with MutSigCV for data preprocessing and ensuring data quality. The Synthetic Minority Over-sampling Technique (SMOTE) up-sampling technique is applied to address the class imbalance representation. Then, Principal Component Analysis (PCA) transforms the DNA methylation, gene expression, and copy number alteration data into a latent space. The purpose is to discard irrelevant variations and extract relevant information. Finally, a classification model is built based on the transformed multiomics data into a unified representation. The framework contributes to understanding the complex interplay between menopause and breast cancer, thereby revealing more precise diagnostic and therapeutic strategies in the future. The explainable artificial intelligence model Shapley based on the XGBoost regressor showed the power of the selected gene expressions for predicting the menopause status, and the potential biomarkers included RUNX1, PTEN, MAP3K1, and CDH1. The literature confirmed the findings.

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.

In the relentless efforts in enhancing medical diagnostics, the integration of state-of-the-art machine learning methodologies has emerged as a promising research area. In molecular biology, there has been an explosion of data generated from multi-omics sequencing. The advent sequencing equipment can provide large number of complicated measurements per one experiment. Therefore, traditional statistical methods face challenging tasks when dealing with such high dimensional data. However, most of the information contained in these datasets is redundant or unrelated and can be effectively reduced to significantly fewer variables without losing much information. Dimensionality reduction techniques are mathematical procedures that allow for this reduction; they have largely been developed through statistics and machine learning disciplines. The other challenge in medical datasets is having an imbalanced number of samples in the classes, which leads to biased results in machine learning models. This study, focused on tackling these challenges in a neural network that incorporates autoencoder to extract latent space of the features, and Generative Adversarial Networks (GAN) to generate synthetic samples. Latent space is the reduced dimensional space that captures the meaningful features of the original data. Our model starts with feature selection to select the discriminative features before feeding them to the neural network. Then, the model predicts the outcome of cancer for different datasets. The proposed model outperformed other existing models by scoring accuracy of 95.09% for bladder cancer dataset and 88.82% for the breast cancer dataset.