Manitz, Juliane

[["dc.bibliographiccitation.firstpage","6742763"],["dc.bibliographiccitation.journal","Computational and mathematical methods in medicine"],["dc.bibliographiccitation.lastpage","17"],["dc.bibliographiccitation.volume","2017"],["dc.contributor.author","Friedrichs, Stefanie"],["dc.contributor.author","Manitz, Juliane"],["dc.contributor.author","Burger, Patricia"],["dc.contributor.author","Amos, Christopher I."],["dc.contributor.author","Risch, Angela"],["dc.contributor.author","Chang-Claude, Jenny"],["dc.contributor.author","Wichmann, Heinz-Erich"],["dc.contributor.author","Kneib, Thomas"],["dc.contributor.author","Bickeböller, Heike"],["dc.contributor.author","Hofner, Benjamin"],["dc.date.accessioned","2018-03-13T14:55:43Z"],["dc.date.available","2018-03-13T14:55:43Z"],["dc.date.issued","2017"],["dc.description.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."],["dc.identifier.doi","10.1155/2017/6742763"],["dc.identifier.pmid","28785300"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14774"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13019"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.relation.eissn","1748-6718"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Pathway-Based Kernel Boosting for the Analysis of Genome-Wide Association Studies"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","64"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Human Heredity"],["dc.bibliographiccitation.lastpage","75"],["dc.bibliographiccitation.volume","76"],["dc.contributor.author","Freytag, Saskia"],["dc.contributor.author","Manitz, Juliane"],["dc.contributor.author","Schlather, Martin"],["dc.contributor.author","Kneib, Thomas"],["dc.contributor.author","Amos, Christopher I."],["dc.contributor.author","Risch, Angela"],["dc.contributor.author","Chang-Claude, Jenny"],["dc.contributor.author","Heinrich, Joachim"],["dc.contributor.author","Bickeböller, Heike"],["dc.date.accessioned","2017-09-07T11:47:18Z"],["dc.date.available","2017-09-07T11:47:18Z"],["dc.date.issued","2014"],["dc.description.abstract","Biological pathways provide rich information and biological context on the genetic causes of complex diseases. The logistic kernel machine test integrates prior knowledge on pathways in order to analyze data from genome-wide association studies (GWAS). In this study, the kernel converts the genomic information of 2 individuals into a quantitative value reflecting their genetic similarity. With the selection of the kernel, one implicitly chooses a genetic effect model. Like many other pathway methods, none of the available kernels accounts for the topological structure of the pathway or gene-gene interaction types. However, evidence indicates that connectivity and neighborhood of genes are crucial in the context of GWAS, because genes associated with a disease often interact. Thus, we propose a novel kernel that incorporates the topology of pathways and information on interactions. Using simulation studies, we demonstrate that the proposed method maintains the type I error correctly and can be more effective in the identification of pathways associated with a disease than non-network-based methods. We apply our approach to genome-wide association case-control data on lung cancer and rheumatoid arthritis. We identify some promising new pathways associated with these diseases, which may improve our current understanding of the genetic mechanisms."],["dc.identifier.doi","10.1159/000357567"],["dc.identifier.gro","3149315"],["dc.identifier.pmid","24434848"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10822"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/5978"],["dc.language.iso","en"],["dc.notes.intern","Kneib Crossref Import"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","public"],["dc.notes.submitter","chake"],["dc.publisher","S. Karger AG"],["dc.relation.eissn","1423-0062"],["dc.relation.issn","0001-5652"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","A Network-Based Kernel Machine Test for the Identification of Risk Pathways in Genome-Wide Association Studies"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","no"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]