Gutenberg Open Science: Dealing with prognostic signature instability : a strategy illustrated for cardiovascular events in patients with end-stage renal disease

Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-7828

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DC Field	Value	Language
dc.contributor.author	Binder, Harald	-
dc.contributor.author	Kurz, Thorsten	-
dc.contributor.author	Teschner, Sven	-
dc.contributor.author	Kreutz, Clemens	-
dc.contributor.author	Geyer, Marcel	-
dc.contributor.author	Donauer, Johannes	-
dc.contributor.author	Kraemer-Guth, Annette	-
dc.contributor.author	Timmer, Jens	-
dc.contributor.author	Schumacher, Martin	-
dc.contributor.author	Walz, Gerd	-
dc.date.accessioned	2022-10-05T08:08:14Z	-
dc.date.available	2022-10-05T08:08:14Z	-
dc.date.issued	2016
dc.identifier.uri	https://openscience.ub.uni-mainz.de/handle/20.500.12030/7843	-
dc.description.abstract	Background Identification of prognostic gene expression markers from clinical cohorts might help to better understand disease etiology. A set of potentially important markers can be automatically selected when linking gene expression covariates to a clinical endpoint by multivariable regression models and regularized parameter estimation. However, this is hampered by instability due to selection from many measurements. Stability can be assessed by resampling techniques, which might guide modeling decisions, such as choice of the model class or the specific endpoint definition. Methods We specifically propose a strategy for judging the impact of different endpoint definitions, endpoint updates, different approaches for marker selection, and exclusion of outliers. This strategy is illustrated for a study with end-stage renal disease patients, who experience a yearly mortality of more than 20 %, with almost 50 % sudden cardiac death or myocardial infarction. The underlying etiology is poorly understood, and we specifically point out how our strategy can help to identify novel prognostic markers and targets for therapeutic interventions. Results For markers such as the potentially prognostic platelet glycoprotein IIb, the endpoint definition, in combination with the signature building approach is seen to have the largest impact. Removal of outliers, as identified by the proposed strategy, is also seen to considerably improve stability. Conclusions As the proposed strategy allowed us to precisely quantify the impact of modeling choices on the stability of marker identification, we suggest routine use also in other applications to prevent analysis-specific results, which are unstable, i.e. not reproducible.	en_GB
dc.description.sponsorship	DFG, Open Access-Publizieren Universität Mainz / Universitätsmedizin	de
dc.language.iso	eng	de
dc.rights	CC BY	*
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/	*
dc.subject.ddc	610 Medizin	de_DE
dc.subject.ddc	610 Medical sciences	en_GB
dc.title	Dealing with prognostic signature instability : a strategy illustrated for cardiovascular events in patients with end-stage renal disease	en_GB
dc.type	Zeitschriftenaufsatz	de
dc.identifier.doi	http://doi.org/10.25358/openscience-7828	-
jgu.type.dinitype	article	en_GB
jgu.type.version	Published version	de
jgu.type.resource	Text	de
jgu.organisation.department	FB 04 Medizin	de
jgu.organisation.number	2700	-
jgu.organisation.name	Johannes Gutenberg-Universität Mainz	-
jgu.rights.accessrights	openAccess	-
jgu.journal.title	BMC medical genomics	de
jgu.journal.volume	9	de
jgu.journal.issue	1	de
jgu.pages.alternative	Art. 43	de
jgu.publisher.year	2016	-
jgu.publisher.name	BioMed Central	de
jgu.publisher.place	London	de
jgu.publisher.uri	http://dx.doi.org/10.1186/s12920-016-0210-9	de
jgu.publisher.issn	1755-8794	de
jgu.organisation.place	Mainz	-
jgu.subject.ddccode	610	de
opus.date.modified	2018-08-23T08:38:39Z
opus.subject.dfgcode	00-000
opus.organisation.string	FB 04: Medizin: Institut für Med. Biometrie, Epidemologie und Informatik	de_DE
opus.identifier.opusid	56381
opus.institute.number	0424
opus.metadataonly	false
opus.type.contenttype	Keine	de_DE
opus.type.contenttype	None	en_EN
opus.affiliated	Binder, Harald
jgu.publisher.doi	10.1186/s12920-016-0210-9	de
jgu.organisation.ror	https://ror.org/023b0x485	-
Appears in collections:	DFG-OA-Publizieren (2012 - 2017)

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