Genome-wide association studies of ischemic stroke based on interpretable machine learning

PeerJ Computer Science. 2024. Vol. 10. Article e2454.

Stefan Nikolić, Ignatov D. I., Khvorykh G., Limborska S., Khrunin A.

 

Despite the identification of several dozen genetic loci associated with ischemic stroke (IS), the genetic bases of this disease remain largely unexplored. In this research we present the results of genome-wide association studies (GWAS) based on classical statistical testing and machine learning algorithms (logistic regression, gradient boosting on decision trees, and tabular deep learning model TabNet). To build a consensus on the results obtained by different techniques, the Pareto-Optimal solution was proposed and applied. These methods were applied to real genotypic data of sick and healthy individuals of European ancestry obtained from the Database of Genotypes and Phenotypes (5,581 individuals, 883,749 single nucleotide polymorphisms). Finally, 131 genes were identified as candidates for association with the onset of IS. UBQLN1, TRPS1, and MUSK were previously described as associated with the course of IS in model animals. ACOT11 taking part in metabolism of fatty acids was shown for the first time to be associated with IS. The identified genes were compared with genes from the Illuminating Druggable Genome project. The product of GPR26 representing the G-coupled protein receptor can be considered as a therapeutic target for stroke prevention. The approaches presented in this research can be used to reprocess GWAS datasets from other diseases.

Keywords: Data Science, bioinformatics, Data Mining and Machine Learning, Neural networks, artificial intelligence

Publication based on the results of: Models and methods for natural language processing, recommendation systems and data mining (2024)