Graph Attention for Alzheimer's Disease Gene Prioritization
T. Verlaan (TU Delft - Electrical Engineering, Mathematics and Computer Science)
Marcel J.T. Reinders – Mentor (TU Delft - Pattern Recognition and Bioinformatics)
G.A. Bouland – Graduation committee member (TU Delft - Pattern Recognition and Bioinformatics)
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Abstract
Identifying key genes in Alzheimer’s Disease (AD) is important in increasing understanding about its pathogenesis, and discovering potential therapeutic targets. Recent advances in single-cell RNA sequencing (scRNAseq) technology have provided unprecedented opportunities to study the molecular mechanisms underlying AD at the cellular level. In this study, we have trained a Graph Attention Network (GAT) to predict disease status of single cells from the SEA-AD scRNAseq dataset. Furthermore, we propose a method for interpreting the learned attention weights of the GAT to score genes on their importance for the prediction, treating gene prioritization as a feature importance problem. We have identified several genes associated with AD, including RBFOX1, NRG1, NRG3, GPC6, HNRNPC and CSMD1. We also found significant gene set enrichment in several terms related to AD and dementia, warranting future research about the presented top genes.