Identification of uveitis-associated functions based on the feature selection analysis of gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment scores

Abstract

Uveitis is a typical type of eye inflammation affecting the middle layer of eye (i.e., uvea layer) and can lead to blindness in middle-aged and young people. Therefore, a comprehensive study determining the disease susceptibility and the underlying mechanisms for uveitis initiation and progression is urgently needed for the development of effective treatments. In the present study, 108 uveitis-related genes are collected on the basis of literature mining, and 17,560 other human genes are collected from the Ensembl database, which are treated as non-uveitis genes. Uveitis- and non-uveitis-related genes are then encoded by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment scores based on the genes and their neighbors in STRING, resulting in 20,681 GO term features and 297 KEGG pathway features. Subsequently, we identify functions and biological processes that can distinguish uveitis-related genes from other human genes by using an integrated feature selection method, which incorporate feature filtering method (Boruta) and four feature importance assessment methods (i.e., LASSO, LightGBM, MCFS, and mRMR). Some essential GO terms and KEGG pathways related to uveitis, such as GO:0001841 (neural tube formation), has04612 (antigen processing and presentation in human beings), and GO:0043379 (memory T cell differentiation), are identified. The plausibility of the association of mined functional features with uveitis is verified on the basis of the literature. Overall, several advanced machine learning methods are used in the current study to uncover specific functions of uveitis and provide a theoretical foundation for the clinical treatment of uveitis.