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

Journal article


Publication Details

Author(s): Friedrichs S, Manitz J, Burger P, Amos CI, Risch A, Chang-Claude J, Wichmann HE, Kneib T, Bickeboeller H, Hofner B
Journal: Computational and Mathematical Methods in Medicine
Publication year: 2017
Volume: 2017
ISSN: 1748-670X
eISSN: 1748-6718


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 considered variables and overcomes the problem of multiple testing. Additionally, it enables the prediction of clinical outcomes. Thus, kernel boosting constitutes a new, powerful tool in the analysis of GWAS data and towards the understanding of biological processes involved in disease susceptibility.


FAU Authors / FAU Editors

Hofner, Benjamin PD Dr.
Lehrstuhl für Biometrie und Epidemiologie


External institutions with authors

Dartmouth College
Deutsches Krebsforschungszentrum (DKFZ)
Georg-August-Universität Göttingen
Ludwig-Maximilians-Universität (LMU)
Universität Salzburg (Paris Lodron Universität Salzburg)


How to cite

APA:
Friedrichs, S., Manitz, J., Burger, P., Amos, C.I., Risch, A., Chang-Claude, J.,... Hofner, B. (2017). Pathway-Based Kernel Boosting for the Analysis of Genome-Wide Association Studies. Computational and Mathematical Methods in Medicine, 2017. https://dx.doi.org/10.1155/2017/6742763

MLA:
Friedrichs, Stefanie, et al. "Pathway-Based Kernel Boosting for the Analysis of Genome-Wide Association Studies." Computational and Mathematical Methods in Medicine 2017 (2017).

BibTeX: 

Last updated on 2018-23-10 at 20:08