{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T03:13:52Z","timestamp":1771125232349,"version":"3.50.1"},"reference-count":34,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T00:00:00Z","timestamp":1605571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["184.034.019"],"award-info":[{"award-number":["184.034.019"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>The goal of metabolomics is to measure as many metabolites as possible in order to capture biomarkers that may indicate disease mechanisms. Variable selection in chemometric methods can be divided into the following two groups: (1) sparse methods that find the minimal set of variables to discriminate between groups and (2) methods that find all variables important for discrimination. Such important variables can be summarized into metabolic pathways using pathway analysis tools like Mummichog. As a test case, we studied the metabolic effects of treatment with nicotinamide riboside, a form of vitamin B3, in a cohort of patients with ataxia\u2013telangiectasia. Vitamin B3 is an important co-factor for many enzymatic reactions in the human body. Thus, the variable selection method was expected to find vitamin B3 metabolites and also other secondary metabolic changes during treatment. However, sparse methods did not select any vitamin B3 metabolites despite the fact that these metabolites showed a large difference when comparing intensity before and during treatment. Univariate analysis or significance multivariate correlation (sMC) in combination with pathway analysis using Mummichog were able to select vitamin B3 metabolites. Moreover, sMC analysis found additional metabolites. Therefore, in our comparative study, sMC displayed the best performance for selection of relevant variables.<\/jats:p>","DOI":"10.3390\/metabo10110470","type":"journal-article","created":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T22:54:17Z","timestamp":1605653657000},"page":"470","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Variable Selection in Untargeted Metabolomics and the Danger of Sparsity"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0758-4128","authenticated-orcid":false,"given":"Gerjen H.","family":"Tinnevelt","sequence":"first","affiliation":[{"name":"Institute for Molecules and Materials, Radboud University, 6525 AJ Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0980-238X","authenticated-orcid":false,"given":"Udo F.H.","family":"Engelke","sequence":"additional","affiliation":[{"name":"Translational Metabolic Laboratory (TML), Department of Laboratory Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2278-9746","authenticated-orcid":false,"given":"Ron A.","family":"Wevers","sequence":"additional","affiliation":[{"name":"Translational Metabolic Laboratory (TML), Department of Laboratory Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefanie","family":"Veenhuis","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7860-7791","authenticated-orcid":false,"given":"Michel A.","family":"Willemsen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karlien L.M.","family":"Coene","sequence":"additional","affiliation":[{"name":"Translational Metabolic Laboratory (TML), Department of Laboratory Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Purva","family":"Kulkarni","sequence":"additional","affiliation":[{"name":"Translational Metabolic Laboratory (TML), Department of Laboratory Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeroen J.","family":"Jansen","sequence":"additional","affiliation":[{"name":"Institute for Molecules and Materials, Radboud University, 6525 AJ Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.aca.2019.12.062","article-title":"Implementation of liquid chromatography\u2013high resolution mass spectrometry methods for untargeted metabolomic analyses of biological samples: A tutorial","volume":"1105","author":"Pezzatti","year":"2020","journal-title":"Anal. 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