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Altenbuchinger, Michael ; Zacharias, Helena ; Solbrig, S. ; Schaefer, Andreas ; Buyukozkan, M. ; Schultheiss, U. T. ; Kotsis, F. ; Köttgen, Anna ; Spang, Rainer ; Oefner, Peter J. ; Krumsiek, J. ; Gronwald, Wolfram

A multi-source data integration approach reveals novel associations between metabolites and renal outcomes in the German Chronic Kidney Disease study

Article

Altenbuchinger, Michael, Zacharias, Helena, Solbrig, S., Schaefer, Andreas, Buyukozkan, M., Schultheiss, U. T. , Kotsis, F., Köttgen, Anna, Spang, Rainer, Oefner, Peter J., Krumsiek, J. and Gronwald, Wolfram (2019) A multi-source data integration approach reveals novel associations between metabolites and renal outcomes in the German Chronic Kidney Disease study. Scientific Reports 9 (1), p. 13954.

DOI to cite this document: 10.5283/epub.40836


Abstract

Omics data facilitate the gain of novel insights into the pathophysiology of diseases and, consequently, their diagnosis, treatment, and prevention. To this end, omics data are integrated with other data types, e.g., clinical, phenotypic, and demographic parameters of categorical or continuous nature. We exemplify this data integration issue for a chronic kidney disease (CKD) study, comprising ...

Omics data facilitate the gain of novel insights into the pathophysiology of diseases and, consequently, their diagnosis, treatment, and prevention. To this end, omics data are integrated with other data types, e.g., clinical, phenotypic, and demographic parameters of categorical or continuous nature. We exemplify this data integration issue for a chronic kidney disease (CKD) study, comprising complex clinical, demographic, and one-dimensional H-1 nuclear magnetic resonance metabolic variables. Routine analysis screens for associations of single metabolic features with clinical parameters while accounting for confounders typically chosen by expert knowledge. This knowledge can be incomplete or unavailable. We introduce a framework for data integration that intrinsically adjusts for confounding variables. We give its mathematical and algorithmic foundation, provide a state-of-the-art implementation, and evaluate its performance by sanity checks and predictive performance assessment on independent test data. Particularly, we show that discovered associations remain significant after variable adjustment based on expert knowledge. In contrast, we illustrate that associations discovered in routine univariate screening approaches can be biased by incorrect or incomplete expert knowledge. Our data integration approach reveals important associations between CKD comorbidities and metabolites, including novel associations of the plasma metabolite trimethylamine-N-oxide with cardiac arrhythmia and infarction in CKD stage 3 patients.



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Details

Item typeArticle
Journal or Publication TitleScientific Reports
PublisherNature
Open Access TypeGold (with APC)
Place of PublicationLONDON
Volume9
Number of Issue or Book Chapter1
Page Rangep. 13954
Date27 September 2019
Date of publication17 Oct 2019 09:01
InstitutionsMedicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner)
Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Statistische Bioinformatik (Prof. Spang)
Informatics and Data Science > Department Computational Life Science > Lehrstuhl für Statistische Bioinformatik (Prof. Spang)

Physics > Institute of Theroretical Physics > Chair Professor Schäfer > Group Andreas Schäfer
Identification Number
ValueType
31562371PubMed ID
10.1038/s41598-019-50346-2DOI
KeywordsRISK-FACTORS; SYSTEMS; PROFILE; COHORT; GOUT; GCKD;
Dewey Decimal Classification500 Science > 530 Physics
600 Technology > 610 Medical sciences Medicine
StatusPublished
RefereedYes, this version has been refereed
Created at the University of RegensburgPartially
URN of the UB Regensburgurn:nbn:de:bvb:355-epub-408360
Item ID40836

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