Author/Editor		Walakira, Andrew; Ocira, Junior; Duroux, Diane; Fouladi, Ramouna; Moškon, Miha; Rozman, Damjana; Van Steen, Kristel
Title		Detecting gene‐gene interactions from GWAS using diffusion kernel principal components
Type		članek
Vol. and No.		, št. Vol. 23
Publication year		2022
Volume		str. 1-18
ISSN		1471-2105 - BMC bioinformatics
Language		eng
Abstract		Genes and gene products do not function in isolation but as components of complex networks of macromolecules through physical or biochemical interactions. Dependen- cies of gene mutations on genetic background (i.e., epistasis) are believed to play a role in understanding molecular underpinnings of complex diseases such as inflammatory bowel disease (IBD). However, the process of identifying such interactions is complex due to for instance the curse of high dimensionality, dependencies in the data and non-linearity. Here, we propose a novel approach for robust and computationally efficient epistasis detection. We do so by first reducing dimensionality, per gene via dif- fusion kernel principal components (kpc). Subsequently, kpc gene summaries are used for downstream analysis including the construction of a gene-based epistasis network. We show that our approach is not only able to recover known IBD associated genes but also additional genes of interest linked to this difficult gastrointestinal disease.
Keywords		inflammatory bowel disease diffusion kernel principal components bivariate synergy vnetna črevesna bolezen glavne komponente difuzijskega jedra bivariatna sinergija