Identification and functional analysis of genes selected using different chemometric techniques on multiarray expression data of liver from high-fat diet treated mice

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The prevalence of obesity is increasing, and this lifestyle disease is related to a high-fat diet, a surplus in caloric intake, and increased inflammation. This study aimed to use a publicly available dataset of microarray gene expression data from the liver of high-fat diet fed mice (GSE39549) to determine the functional importance of small subsets of the overall genes. The regulatory aspects of the chosen mice genes were extrapolated to human genes for the determination of potential diagnostic and therapeutic targets. The chemometric approaches of principal component analysis (PCA), random forest (RF), and genetic algorithm (GA) were used as data reduction techniques to select 50 genes from a total of 15,000 genes to differentiate liver samples from high-fat diet and normal diet-fed mice. A subset of 30 genes from each of the techniques were processed with classification techniques of k-nearest neighbor and support vector machines. The results showed that random forest was best at differentiating the samples and GA was the least accurate. The results of functional annotation and protein-protein interactions showed that genes selected by PCA and RF were more associated with obesity as they identified functions related to inflammatory processes, as well as lipid and cholesterol metabolic processes. The genes selected by GA identified processes related to cilium and cell projection. The proteins identified by RF, such as Msmo and Sqle, had roles in cholesterol metabolic and biosynthetic processes. The results showed that combining the genes selected by PCA and RF allowed a better understanding of the overall functional protein modules. The crosstalk genes such as Abcg5 as well as Abcg8 that relate cholesterol metabolic and biosynthetic process to glutathione metabolic process were identified. Various miRNAs-gene interactions are present in humans for most of the genes identified by PCA, RF, or GA. Some genes that showed fewer interactions with human miRNAs are CIDEA, PLIN4, and NME8. The results suggest the use of different chemometric analyses in combination with functional genomics to identify different sets of targets for diagnostic, therapeutic, and future research.