{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T04:45:06Z","timestamp":1778561106083,"version":"3.51.4"},"reference-count":32,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T00:00:00Z","timestamp":1614124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wereld Kanker Onderzoek Fonds (WKOF) &amp; World Cancer Research Fund International (WCRF International); the World Cancer Research Fund Inter-national Regular Grant Programme","award":["no. 2014\/1179"],"award-info":[{"award-number":["no. 2014\/1179"]}]},{"name":"Alpe d\u2019Huzes\/Dutch Cancer Society (KWF Kankerbestrijding, the Nether-lands, project","award":["no. UM 2012-5653, UW 2013-5927, UW 2015-7946"],"award-info":[{"award-number":["no. UM 2012-5653, UW 2013-5927, UW 2015-7946"]}]},{"name":"ERA-NET on Translational Cancer Research (TRANSCAN\/Dutch Cancer So-ciety, the Netherlands","award":["project no. UW 2013-6397, UW 2014-6877"],"award-info":[{"award-number":["project no. UW 2013-6397, UW 2014-6877"]}]},{"name":"ERA-NET on Translational Cancer Research (TRANSCAN\/Dutch Cancer So-ciety, the Netherlands","award":["project no. UM 2014-6877"],"award-info":[{"award-number":["project no. UM 2014-6877"]}]},{"name":"the Netherlands Organization for Health Research and Development (ZonMw, the Netherlands)","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"Stichting Alpe d'HuZes within the research program 'Leven met kanker' of the Dutch Cancer Society","award":["Grant No. UM-2010-4867 and UM-2012-5653"],"award-info":[{"award-number":["Grant No. UM-2010-4867 and UM-2012-5653"]}]},{"name":"grants from Kankeronderzoekfonds Limburg as part of Health Foundation Limburg","award":["Grant No. 00005739"],"award-info":[{"award-number":["Grant No. 00005739"]}]},{"name":"Wereld Kanker Onderzoek Fonds (WKOF), as part of the World Cancer Re-search Fund International grant programme","award":["grant number 2016\/1620"],"award-info":[{"award-number":["grant number 2016\/1620"]}]},{"name":"E.H. van Roekel is funded by the Wereld Kanker Onderzoek Fonds (WKOF), as part of the World Cancer Research Fund International grant programme","award":["grant number 2016\/1620"],"award-info":[{"award-number":["grant number 2016\/1620"]}]},{"name":"ERA-NET on Translational Cancer Research (TRANSCAN)","award":["project 01KT1503"],"award-info":[{"award-number":["project 01KT1503"]}]},{"name":"Federal Ministry of Education and Research), the National Cancer Institute","award":["project 01KT1503"],"award-info":[{"award-number":["project 01KT1503"]}]},{"name":"the Stiftung Lebensblicke","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"DOI":"10.13039\/100017403","name":"Matthias Lackas Foundation","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100017403","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institutes of Health\/National Cancer Institute","award":["U01CA206110"],"award-info":[{"award-number":["U01CA206110"]}]},{"name":"National Institutes of Health\/National Cancer Institute","award":["R01 CA207371"],"award-info":[{"award-number":["R01 CA207371"]}]},{"name":"National Institutes of Health\/National Cancer Institute","award":["R01CA189184"],"award-info":[{"award-number":["R01CA189184"]}]},{"name":"Austrian Science Fund (FWF)","award":["grant no: 1578-B19"],"award-info":[{"award-number":["grant no: 1578-B19"]}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["France, project no. 2014-007"],"award-info":[{"award-number":["France, project no. 2014-007"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"name":"A.N.H. was supported by the National Institutes of Health under Ruth L. Kirschstein National Research Service Award T32","award":["HG008962"],"award-info":[{"award-number":["HG008962"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>The identification of patients at high-risk for colorectal cancer (CRC) recurrence remains an unmet clinical need. The aim of this study was to investigate associations of metabolites with risk of recurrence in stage II\/III CRC patients. A targeted metabolomics assay (128 metabolites measured) was performed on pre-surgery collected EDTA plasma samples from n = 440 newly diagnosed stage II\/III CRC patients. Patients have been recruited from four prospective cohort studies as part of an international consortium: Metabolomic profiles throughout the continuum of CRC (MetaboCCC). Cox proportional hazard models were computed to investigate associations of metabolites with recurrence, adjusted for age, sex, tumor stage, tumor site, body mass index, and cohort; false discovery rate (FDR) was used to account for multiple testing. Sixty-nine patients (15%) had a recurrence after a median follow-up time of 20 months. We identified 13 metabolites that were nominally associated with a reduced risk of recurrence. None of the associations were statistically significant after controlling for multiple testing. Pathway topology analyses did not reveal statistically significant associations between recurrence and alterations in metabolic pathways (e.g., sphingolipid metabolism p = 0.04; pFDR = 1.00). To conclude, we did not observe statistically significant associations between metabolites and CRC recurrence using a well-established metabolomics assay. The observed results require follow-up in larger studies.<\/jats:p>","DOI":"10.3390\/metabo11030129","type":"journal-article","created":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T02:36:13Z","timestamp":1614220573000},"page":"129","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Targeted Plasma Metabolic Profiles and Risk of Recurrence in Stage II and III Colorectal Cancer Patients: Results from an International Cohort Consortium"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2030-9676","authenticated-orcid":false,"given":"Jennifer","family":"Ose","sequence":"first","affiliation":[{"name":"Huntsman Cancer Institute Salt Lake City, Salt Lake City, UT 84112, USA"},{"name":"Department of Population Health Sciences, University of Utah, Salt Lake City, UT 84112, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8085-2072","authenticated-orcid":false,"given":"Biljana","family":"Gigic","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Transplantation Surgery, University of Heidelberg, 1, 69117 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5238-6900","authenticated-orcid":false,"given":"Stefanie","family":"Brezina","sequence":"additional","affiliation":[{"name":"Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, 23, 1090 Wien, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tengda","family":"Lin","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute Salt Lake City, Salt Lake City, UT 84112, USA"},{"name":"Department of Population Health Sciences, University of Utah, Salt Lake City, UT 84112, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5329-9507","authenticated-orcid":false,"given":"Andreas","family":"Baierl","sequence":"additional","affiliation":[{"name":"Department of Statistics and Operations Research, University of Vienna, 1, 1010 Wien, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne J. M. R.","family":"Geijsen","sequence":"additional","affiliation":[{"name":"Division of Human Nutrition and Health, Wageningen University &amp; Research, 6708 Wageningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9402-2029","authenticated-orcid":false,"given":"Eline","family":"van Roekel","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, GROW-School of Oncology and Developmental Biology, Maastricht University, 30, 6229 Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2532-1455","authenticated-orcid":false,"given":"Nivonirina","family":"Robinot","sequence":"additional","affiliation":[{"name":"Biomarkers Group, International Agency for Research on Cancer, 69372 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Audrey","family":"Gicquiau","sequence":"additional","affiliation":[{"name":"Biomarkers Group, International Agency for Research on Cancer, 69372 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Achaintre","sequence":"additional","affiliation":[{"name":"Biomarkers Group, International Agency for Research on Cancer, 69372 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pekka","family":"Keski-Rahkonen","sequence":"additional","affiliation":[{"name":"Biomarkers Group, International Agency for Research on Cancer, 69372 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fr\u00e4nzel J. B.","family":"van Duijnhoven","sequence":"additional","affiliation":[{"name":"Division of Human Nutrition and Health, Wageningen University &amp; Research, 6708 Wageningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9319-5350","authenticated-orcid":false,"given":"Tanja","family":"Gumpenberger","sequence":"additional","affiliation":[{"name":"Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, 23, 1090 Wien, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8001-8793","authenticated-orcid":false,"given":"Andreana N.","family":"Holowatyj","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute Salt Lake City, Salt Lake City, UT 84112, USA"},{"name":"Department of Population Health Sciences, University of Utah, Salt Lake City, UT 84112, USA"},{"name":"Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA"},{"name":"Vanderbilt-Ingram Cancer Center, Nashville, TN 37232, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7154-8207","authenticated-orcid":false,"given":"Dieuwertje E.","family":"Kok","sequence":"additional","affiliation":[{"name":"Division of Human Nutrition and Health, Wageningen University &amp; Research, 6708 Wageningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9927-9034","authenticated-orcid":false,"given":"Annaleen","family":"Koole","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, GROW-School of Oncology and Developmental Biology, Maastricht University, 30, 6229 Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra","family":"Schrotz-King","sequence":"additional","affiliation":[{"name":"Division of Preventive Oncology, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), 460, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexis B.","family":"Ulrich","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Transplantation Surgery, University of Heidelberg, 1, 69117 Heidelberg, Germany"},{"name":"Klinik f\u00fcr Allgemein-, Viszeral-, Thorax- und Gef\u00e4\u00dfchirurgie, St\u00e4dtische Kliniken Neuss, 84, 41464 Neuss, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Transplantation Surgery, University of Heidelberg, 1, 69117 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arve","family":"Ulvik","sequence":"additional","affiliation":[{"name":"BEVITAL, 87, 5021 Bergen, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Per-Magne","family":"Ueland","sequence":"additional","affiliation":[{"name":"BEVITAL, 87, 5021 Bergen, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matty P.","family":"Weijenberg","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, GROW-School of Oncology and Developmental Biology, Maastricht University, 30, 6229 Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nina","family":"Habermann","sequence":"additional","affiliation":[{"name":"Genome Biology, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6651-6710","authenticated-orcid":false,"given":"Augustin","family":"Scalbert","sequence":"additional","affiliation":[{"name":"Biomarkers Group, International Agency for Research on Cancer, 69372 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9795-1528","authenticated-orcid":false,"given":"Andrea","family":"Gsur","sequence":"additional","affiliation":[{"name":"Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, 23, 1090 Wien, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7641-059X","authenticated-orcid":false,"given":"Cornelia M.","family":"Ulrich","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute Salt Lake City, Salt Lake City, UT 84112, USA"},{"name":"Department of Population Health Sciences, University of Utah, Salt Lake City, UT 84112, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,24]]},"reference":[{"key":"ref_1","unstructured":"American Cancer Society (2005). Cancer Facts & Figures, American Cancer Society."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","unstructured":"Gelband, H., Jha, P., Sankaranarayanan, R., and Horton, S. (2015). Colorectal Cancer. Cancer: Disease Control Priorities, The World Bank. [3rd ed.]."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1056\/NEJMoa1713709","article-title":"Duration of Adjuvant Chemotherapy for Stage III Colon Cancer","volume":"378","author":"Grothey","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2336","DOI":"10.1200\/JCO.2007.15.8261","article-title":"Survival following recurrence in stage II and III colon cancer: Findings from the ACCENT data set","volume":"26","author":"Campbell","year":"2008","journal-title":"J. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2740","DOI":"10.1245\/s10434-020-08238-7","article-title":"Predicting Risk of Recurrence After Colorectal Cancer Surgery in the United States: An Analysis of a Special Commission on Cancer National Study","volume":"27","author":"Zafar","year":"2020","journal-title":"Ann. Surg. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"363","DOI":"10.3322\/caac.21565","article-title":"Cancer treatment and survivorship statistics, 2019","volume":"69","author":"Miller","year":"2019","journal-title":"CA Cancer J Clin"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1002\/cncr.21204","article-title":"Differences in colorectal carcinoma stage and survival by race and ethnicity","volume":"104","author":"Chien","year":"2005","journal-title":"Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"637","DOI":"10.3945\/ajcn.116.150912","article-title":"Nutritional metabolomics and breast cancer risk in a prospective study","volume":"106","author":"Playdon","year":"2017","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"450","DOI":"10.3945\/ajcn.116.144501","article-title":"Identifying biomarkers of dietary patterns by using metabolomics","volume":"105","author":"Playdon","year":"2017","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1002\/ijc.32146","article-title":"Plasma metabolites associated with colorectal cancer: A discovery-replication strategy","volume":"145","author":"Geijsen","year":"2019","journal-title":"Int. J. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Delphan, M., Lin, T., Liesenfeld, D.B., Nattenmuller, J., Bohm, J.T., Gigic, B., Habermann, N., Zielske, L., Schrotz-King, P., and Schneider, M. (2018). Associations of branched-chain amino acids with parameters of energy balance and survival in colorectal cancer patients: Results from the ColoCare Study. Metab. Off. J. Metab. Soc., 2018.","DOI":"10.1007\/s11306-017-1314-8"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Erben, V., Bhardwaj, M., Schrotz-King, P., and Brenner, H. (2018). Metabolomics Biomarkers for Detection of Colorectal Neoplasms: A Systematic Review. Cancers, 10.","DOI":"10.3390\/cancers10080246"},{"key":"ref_14","unstructured":"Adamski, J. (2020). Metabolomics for Biomedical Research, Elsevier."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3256","DOI":"10.1002\/ijc.32666","article-title":"Plasma metabolites associated with colorectal cancer stage: Findings from an international consortium","volume":"146","author":"Geijsen","year":"2020","journal-title":"Int. J. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"167","DOI":"10.2174\/1874467211104030167","article-title":"Glycerophospholipid synthesis as a novel drug target against cancer","volume":"4","author":"Dolce","year":"2011","journal-title":"Curr. Mol. Pharm."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1111\/cas.12221","article-title":"Accumulated phosphatidylcholine (16:0\/16:1) in human colorectal cancer; possible involvement of LPCAT4","volume":"104","author":"Kurabe","year":"2013","journal-title":"Cancer Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"39999","DOI":"10.1038\/srep39999","article-title":"Nesting of colon and ovarian cancer cells in the endothelial niche is associated with alterations in glycan and lipid metabolism","volume":"7","author":"Halama","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1007\/s10552-020-01312-1","article-title":"Metabolomics profiling of visceral and abdominal subcutaneous adipose tissue in colorectal cancer patients: Results from the ColoCare study","volume":"31","author":"Ose","year":"2020","journal-title":"Cancer Causes Control"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1021\/acs.analchem.6b02930","article-title":"Interlaboratory Reproducibility of a Targeted Metabolomics Platform for Analysis of Human Serum and Plasma","volume":"89","author":"Siskos","year":"2017","journal-title":"Anal. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Carayol, M., Licaj, I., Achaintre, D., Sacerdote, C., Vineis, P., Key, T.J., Onland Moret, N.C., Scalbert, A., Rinaldi, S., and Ferrari, P. (2015). Reliability of Serum Metabolites over a Two-Year Period: A Targeted Metabolomic Approach in Fasting and Non-Fasting Samples from EPIC. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0135437"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Breier, M., Wahl, S., Prehn, C., Fugmann, M., Ferrari, U., Weise, M., Banning, F., Seissler, J., Grallert, H., and Adamski, J. (2014). Targeted metabolomics identifies reliable and stable metabolites in human serum and plasma samples. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0089728"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1158\/1055-9965.EPI-12-1109","article-title":"Metabolomics in epidemiology: Sources of variability in metabolite measurements and implications","volume":"22","author":"Sampson","year":"2013","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Winkels, R.M., Heine-Broring, R.C., van Zutphen, M., van Harten-Gerritsen, S., Kok, D.E., van Duijnhoven, F.J., and Kampman, E. (2014). The COLON study: Colorectal cancer: Longitudinal, Observational study on Nutritional and lifestyle factors that may influence colorectal tumour recurrence, survival and quality of life. BMC Cancer, 14.","DOI":"10.1186\/1471-2407-14-374"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1158\/1055-9965.EPI-13-1144","article-title":"The applicability of the international classification of functioning, disability, and health to study lifestyle and quality of life of colorectal cancer survivors","volume":"23","author":"Bours","year":"2014","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1158\/1055-9965.EPI-18-0773","article-title":"The ColoCare Study: A Paradigm of Transdisciplinary Science in Colorectal Cancer Outcomes","volume":"28","author":"Ulrich","year":"2019","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Brierley, J.D., Gospodarowicz, M.K., and Wittekind, C. (2016). TNM Classification of Malignant Tumours, John Wiley & Sons.","DOI":"10.1002\/9780471420194.tnmc26.pub3"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Van Roekel, E.H., Trijsburg, L., Assi, N., Carayol, M., Achaintre, D., Murphy, N., Rinaldi, S., Schmidt, J.A., Stepien, M., and Kaaks, R. (2018). Circulating metabolites associated with alcohol intake in the european prospective investigation into cancer and nutrition cohort. Nutrients, 10.","DOI":"10.3390\/nu10050654"},{"key":"ref_29","first-page":"93","article-title":"Non-targeted UHPLC-MS metabolomic data processing methods: A comparative investigation of normalisation, missing value imputation, transformation and scaling","volume":"12","author":"Engel","year":"2016","journal-title":"Metab. Off. J. Metab. Soc."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1080\/00401706.1983.10487848","article-title":"Percentage points for a generalized esd many-outlier procedure","volume":"25","author":"Rosner","year":"1983","journal-title":"Technometrics"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Soc. Ser. B"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e86","DOI":"10.1002\/cpbi.86","article-title":"Using MetaboAnalyst 4.0 for Comprehensive and Integrative Metabolomics Data Analysis","volume":"68","author":"Chong","year":"2019","journal-title":"Curr. Protoc. Bioinform."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/11\/3\/129\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:28:01Z","timestamp":1760160481000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/11\/3\/129"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,24]]},"references-count":32,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["metabo11030129"],"URL":"https:\/\/doi.org\/10.3390\/metabo11030129","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,24]]}}}