Empowering individual trait prediction using interactions

Abstract: One component of precision medicine is to construct prediction models with their predictive ability as high as possible, e.g. to enable individual risk prediction. In genetic epidemiology, complex diseases have a polygenic basis and a common assumption is that biological and genetic features affect the outcome under consideration via interactions. In the case of omics data, the use of standard approaches such as generalized linear models may be suboptimal and machine learning methods are appealing to make individual predictions. However, most of these algorithms focus mostly on main or marginal effects of the single features in a dataset. On the other hand, the detection of interacting features is an active area of research in the realm of genetic epidemiology. One big class of algorithms to detect interacting features is based on the multifactor dimensionality reduction (MDR). Here, we extend the model-based MDR (MB-MDR), a powerful extension of the original MDR algorithm, to enable interaction empowered individual prediction. Using a comprehensive simulation study we show that our new algorithm can use information hidden in interactions more efficiently than two other state-of-the-art algorithms, namely the Random Forest and Elastic Net, and clearly outperforms these if interactions are present. The performance of these algorithms is comparable if no interactions are present. Further, we show that our new algorithm is applicable to real data by comparing the performance of the three algorithms on a dataset of rheumatoid arthritis cases and healthy controls. As our new algorithm is not only applicable to biological/genetic data but to all datasets with discrete features, it may have practical implications in other applications as well, and we made our method available as an R package.