An Associative Classification Based Approach for Detecting SNP-SNP Interactions in High Dimensional Genome

摘要

There have been many studies that depict genotype-phenotype relationships by identifying genetic variants associated with a specific disease. Researchers focus more attention on interactions between SNPs that are strongly associated with disease in the absence of main effect. In this context, a number of machine learning and data mining tools are applied to identify the combinations of multi-locus SNPs in higher order data. However, none of the current models can identify useful SNP-SNP interactions for high dimensional genome data. Detecting these interactions is challenging due to bio-molecular complexities and computational limitations. The goal of this research was to implement associative classification and study its effectiveness for detecting the epistasis in balanced and imbalanced datasets. The proposed approach was evaluated for two locus epistasis interactions using simulated data. The datasets were generated for 5 different penetrance functions by varying heritability, minor allele frequency and sample size. In total, 23,400 datasets were generated and several experiments are conducted to identify the disease causal SNP interactions. The accuracy of classification by the proposed approach was compared with the previous approaches. Though associative classification showed only relatively small improvement in accuracy for balanced datasets, it outperformed existing approaches in higher order multi-locus interactions in imbalanced datasets.