Improved One-Class Modeling of High-Dimensional Metabolomics Data via Eigenvalue-Shrinkage

A. Brini*, V. Avagyan, C.H. de Vos, J.H. Vossen, Edwin R. van den Heuvel, J. Engel

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)


One-class modelling is a useful approach in metabolomics for the untargeted detection of abnormal metabolite profiles, when information from a set of reference observations is available to model “normal” or baseline metabolite profiles. Such outlying profiles are typically identified by comparing the distance between an observation and the reference class to a critical limit. Often,
multivariate distance measures such as the Mahalanobis distance (MD) or principal component-based measures are used. These approaches, however, are either not applicable to untargeted metabolomics data, or their results are unreliable. In this paper, five distance measures for one-class modeling in
untargeted metabolites are proposed. They are based on a combination of the MD and five so-called eigenvalue-shrinkage estimators of the covariance matrix of the reference class. A simple crossvalidation procedure is proposed to set the critical limit for outlier detection. Simulation studies are used to identify which distance measure provides the best performance for one-class modeling,
in terms of type I error and power to identify abnormal metabolite profiles. Empirical evidence demonstrates that this method has better type I error (false positive rate) and improved outlier detection power than the standard (principal component-based) one-class models. The method is illustrated by its application to liquid chromatography coupled to mass spectrometry (LC-MS) and
nuclear magnetic response spectroscopy (NMR) untargeted metabolomics data from two studies on food safety assessment and diagnosis of rare diseases, respectively.
Original languageEnglish
Article number237
Issue number4
Publication statusPublished - 13 Apr 2021


  • Critical value
  • Eigenvalue-shrinkage
  • High-dimensional data
  • Mahalonobis distance
  • One-class model
  • Scaled Chi-square distribution
  • Untargeted metabolomics


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