Machine Learning Model for Multiomics Biomarkers Identification for Menopause Status in Breast Cancer

Abstract

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.