Pathway-based kernel boosting for the analysis of genome-wide association studies
type: Item
instance of: scholarly article
title: Pathway-based kernel boosting for the analysis of genome-wide association studies
zbMATH Open document ID: 1382.92127
DOI: 10.1155/2017/6742763
author: Stefanie Friedrichs
author: Juliane Manitz
author: Patricia Burger
author: Christopher I. Amos
author: Angela Risch
author: Jenny Chang-Claude
author: H.-Erich Wichmann
author: Thomas Kneib
author: Heike Bickeböller
author: Benjamin Hofner
published in: Computational \& Mathematical Methods in Medicine
publication date: 2018-03-15T00:00:00Z
review text: Summary: 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.
Mathematics Subject Classification ID: 92C40
Mathematics Subject Classification ID: 92-08
zbMATH DE Number: 6850533
zbMATH Keywords: genome-wide association studies
zbMATH Keywords: gene-interaction networks
zbMATH Keywords: kernel boosting
Wikidata QID: Q38635886
describes a project that uses: Bioconductor
describes a project that uses: mboost
describes a project that uses: R
describes a project that uses: KEGG
describes a project that uses: HAPGEN2
MaRDI profile type: Publication
full work available at URL: https://doi.org/10.1155/2017/6742763
OpenAlex ID: W2735194812
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DBLP publication ID: journals/cmmm/FriedrichsMBARC17
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description: scientific article; zbMATH DE number 6850533