Abstract

BackgroundCalcific aortic valve stenosis (CAVS) is a fatal disease and there is no pharmacological treatment to prevent the progression of CAVS. This study aims to identify genes potentially implicated with CAVS in patients with congenital bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) in comparison with patients having normal valves, using a knowledge-slanted random forest (RF).ResultsThis study implemented a knowledge-slanted random forest (RF) using information extracted from a protein-protein interactions network to rank genes in order to modify their selection probability to draw the candidate split-variables. A total of 15,191 genes were assessed in 19 valves with CAVS (BAV, n = 10; TAV, n = 9) and 8 normal valves. The performance of the model was evaluated using accuracy, sensitivity, and specificity to discriminate cases with CAVS. A comparison with conventional RF was also performed. The performance of this proposed approach reported improved accuracy in comparison with conventional RF to classify cases separately with BAV and TAV (Slanted RF: 59.3% versus 40.7%). When patients with BAV and TAV were grouped against patients with normal valves, the addition of prior biological information was not relevant with an accuracy of 92.6%.ConclusionThe knowledge-slanted RF approach reflected prior biological knowledge, leading to better precision in distinguishing between cases with BAV, TAV, and normal valves. The results of this study suggest that the integration of biological knowledge can be useful during difficult classification tasks.

Highlights

  • Calcific aortic valve stenosis (CAVS) is one of the main causes of morbidity and mortality in the elderly

  • The clustering of sample points evidenced that cases with bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) share similar level gene expression profiles, with differences compared to the controls

  • The performance of knowledge-slanted random forest (RF) was better than RF when comparing CAVS patients with BAV or TAV with accuracies of 54.6 ± 6.5 and 43.0% ± 7.1%, respectively

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Summary

Introduction

Calcific aortic valve stenosis (CAVS) is one of the main causes of morbidity and mortality in the elderly. A normal aortic valve has three leaflets, a congenital bicuspid aortic valve (BAV). Patients with BAV and tricuspid aortic valve (TAV) are susceptible to develop CAVS and its etiology can be classified as congenital or degenerative associated with a chronic process by progressive mineralization. The identification of candidate genes that are relevant in the CAVS process is imperative to improve the understanding of the mechanisms behind calcified BAV and TAV and discover potential medical treatments. Calcific aortic valve stenosis (CAVS) is a fatal disease and there is no pharmacological treatment to prevent the progression of CAVS. This study aims to identify genes potentially implicated with CAVS in patients with congenital bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) in comparison with patients having normal valves, using a knowledge-slanted random forest (RF)

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