An Enhanced Random Forests Approach to Predict Heart Failure from Small Imbalanced Gene Expression Data

Myocardial infarctions and heart failure are the cause of more than 17 million deaths annually worldwide. ST-segment elevation myocardial infarctions (STEMI) require timely treatment, because delays of minutes have serious clinical impacts. Machine learning can provide alternative ways to predict heart failure and identify genes involved in heart failure. For these scopes, we applied a Random Forests classifier enhanced with feature elimination to microarray gene expression of 111 patients diagnosed with STEMI, and measured the classification performance through standard metrics such as the Matthews correlation coefficient (MCC) and area under the receiver operating characteristic curve (ROC AUC). Afterwards, we used the same approach to rank all genes by importance, and to detect the genes more strongly associated with heart failure. We validated this ranking by literature review and gene set enrichment analysis. Our classifier employed to predict heart failure achieved MCC = +0.87 and ROC AUC = 0.918, and our analysis identified KLHL22, WDR11, OR4Q3, GPATCH3, and FAH as top five protein-coding genes related to heart failure. Our results confirm the effectiveness of machine learning feature elimination in predicting heart failure from gene expression, and the top genes found by our approach will be able to help biologists and cardiologists further our understanding of heart failure.