A deep learning model for early risk prediction of heart failure with preserved ejection fraction by DNA methylation profiles combined with clinical features.

ABSTRACT:

Background

Heart failure with preserved ejection fraction (HFpEF), affected collectively by genetic and environmental factors, is the common subtype of chronic heart failure. Although the available risk assessment methods for HFpEF have achieved some progress, they were based on clinical or genetic features alone. Here, we have developed a deep learning framework, HFmeRisk, using both 5 clinical features and 25 DNA methylation loci to predict the early risk of HFpEF in the Framingham Heart Study Cohort.

Results

The framework incorporates Least Absolute Shrinkage and Selection Operator and Extreme Gradient Boosting-based feature selection, as well as a Factorization-Machine based neural network-based recommender system. Model discrimination and calibration were assessed using the AUC and Hosmer-Lemeshow test. HFmeRisk, including 25 CpGs and 5 clinical features, have achieved the AUC of 0.90 (95% confidence interval 0.88-0.92) and Hosmer-Lemeshow statistic was 6.17 (P = 0.632), which outperformed models with clinical characteristics or DNA methylation levels alone, published chronic heart failure risk prediction models and other benchmark machine learning models. Out of them, the DNA methylation levels of two CpGs were significantly correlated with the paired transcriptome levels (R < -0.3, P < 0.05). Besides, DNA methylation locus in HFmeRisk were associated with intercellular signaling and interaction, amino acid metabolism, transport and activation and the clinical variables were all related with the mechanism of occurrence of HFpEF. Together, these findings give new evidence into the HFmeRisk model.

Conclusion

Our study proposes an early risk assessment framework for HFpEF integrating both clinical and epigenetic features, providing a promising path for clinical decision making.

SUBMITTER: Zhao X 

PROVIDER: S-EPMC8772140 | biostudies-literature |

REPOSITORIES: biostudies-literature