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Characterization of missing values in untargeted MS-based metabolomics data and evaluation of missing data handling strategies.
Metabolomics 14 (2018)
online verfügbar vsl. 09/2019 
BackgroundUntargeted mass spectrometry (MS)-based metabolomics data often contain missing values that reduce statistical power and can introduce bias in biomedical studies. However, a systematic assessment of the various sources of missing values and strategies to handle these data has received little attention. Missing data can occur systematically, e.g. from run day-dependent effects due to limits of detection (LOD); or it can be random as, for instance, a consequence of sample preparation.MethodsWe investigated patterns of missing data in an MS-based metabolomics experiment of serum samples from the German KORA F4 cohort (n=1750). We then evaluated 31 imputation methods in a simulation framework and biologically validated the results by applying all imputation approaches to real metabolomics data. We examined the ability of each method to reconstruct biochemical pathways from data-driven correlation networks, and the ability of the method to increase statistical power while preserving the strength of established metabolic quantitative trait loci.ResultsRun day-dependent LOD-based missing data accounts for most missing values in the metabolomics dataset. Although multiple imputation by chained equations performed well in many scenarios, it is computationally and statistically challenging. K-nearest neighbors (KNN) imputation on observations with variable pre-selection showed robust performance across all evaluation schemes and is computationally more tractable.ConclusionMissing data in untargeted MS-based metabolomics data occur for various reasons. Based on our results, we recommend that KNN-based imputation is performed on observations with variable pre-selection since it showed robust results in all evaluation schemes.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Untargeted Metabolomics ; Missing Values Imputation ; Limit Of Detection ; Batch Effects ; Mice ; K-nearest Neighbor ; Mass Spectrometry; Multiple Imputation; Human Blood; Networks; Limit
ISSN (print) / ISBN 1573-3882
e-ISSN 1573-3890
Zeitschrift Metabolomics
Quellenangaben Band: 14, Heft: 10 Seiten: , Artikelnummer: , Supplement: ,
Verlag Springer
Verlagsort New York, NY
Begutachtungsstatus peer-reviewed