The Application of Michigan-Style Learning Classifier Systems to Address Genetic Heterogeneity and Epistasis in Association Studies

摘要

Genetic epidemiologists, tasked with the disentanglement of genotype-to-phenotype mappings, continue to struggle with a variety of phenomena which obscure the underlying etiologies of common complex diseases. For genetic association studies, genetic heterogeneity (GH) and epistasis (gene-gene interactions) epitomize well recognized phenomenon which represent a difficult, but accessible challenge for computational biologists. While progress has been made addressing epistasis, methods for dealing with GH tend to "side-step" the problem, limited by a dependence on potentially arbitrary cutoffs/covariates, and a loss in power synonymous with data stratification. In the present study, we explore an alternative strategy (Learning Classifier Systems (LCSs)) as a direct approach for the characterization, and modeling of disease in the presence of both GH and epistasis. This evaluation involves (1) implementing standardized versions of existing Michigan-Style LCSs (XCS, MCS, and UCS), (2) examining major run parameters, and (3) performing quantitative and qualitative evaluations across a spectrum of simulated datasets. The results of this study highlight the strengths and weaknesses of the Michigan LCS architectures examined, providing proof of principle for the application of LCSs to the GH/epistasis problem, and laying the foundation for the development of an LCS algorithm specifically designed to address GH.