Pathway-Based Kernel Boosting for the Analysis of Genome-Wide Association Studies.

Pathway-Based Kernel Boosting for the Analysis of Genome-Wide Association Studies. Comput Math Methods Med. 2017;2017:6742763 Authors: Friedrichs S, Manitz J, Burger P, Amos CI, Risch A, Chang-Claude J, Wichmann HE, Kneib T, Bickeböller H, Hofner B Abstract The analysis of genome-wide association studies (GWAS) benefits from the investigation of biologically meaningful gene sets, such as gene-interaction networks (pathways). We propose an extension to a successful kernel-based pathway analysis approach by integrating kernel functions into a powerful algorithmic framework for variable selection, to enable investigation of multiple pathways simultaneously. We employ genetic similarity kernels from the logistic kernel machine test (LKMT) as base-learners in a boosting algorithm. A model to explain case-control status is created iteratively by selecting pathways that improve its prediction ability. We evaluated our method in simulation studies adopting 50 pathways for different sample sizes and genetic effect strengths. Additionally, we included an exemplary application of kernel boosting to a rheumatoid arthritis and a lung cancer dataset. Simulations indicate that kernel boosting outperforms the LKMT in certain genetic scenarios. Applications to GWAS data on rheumatoid arthritis and lung cancer resulted in sparse models which were based on pathways interpretable in a clinical sense. Kernel boosting is highly flexible in terms of consi...
Source: Computational and Mathematical Methods in Medicine - Category: Statistics Tags: Comput Math Methods Med Source Type: research