Title
Large-scale human metabolomics studies: A strategy for data (pre-) processing and validation
Author
Bijlsma, S.
Bobeldijk, I.
Verheij, E.R.
Ramaker, R.
Kochhar, S.
Macdonald, I.A.
van Ommen, B.
Smilde, A.K.
TNO Kwaliteit van Leven
Publication year
2006
Abstract
A large metabolomics study was performed on 600 plasma samples taken at four time points before and after a single intake of a high fat test meal by obese and lean subjects. All samples were analyzed by a liquid chromatography-mass spectrometry (LC-MS) lipidomic method for metabolic profiling. A pragmatic approach combining several well-established statistical methods was developed for processing this large data set in order to detect small differences in metabolic profiles in combination with a large biological variation. Such metabolomics studies require a careful analytical and statistical protocol. The strategy included data preprocessing, data analysis, and validation of statistical models. After several data preprocessing steps, partial least-squares discriminant analysis (PLS-DA) was used for finding biomarkers. To validate the found biomarkers statistically, the PLS-DA models were validated by means of a permutation test, biomarker models, and noninformative models. Univariate plots of potential biomarkers were used to obtain insight in up- or downregulation. The strategy proposed proved to be applicable for dealing with large-scale human metabolomics studies. © 2006 American Chemical Society.
Subject
Biology
Analytical research
Biomedical research
Data processing
Data reduction
Liquid chromatography
Mass spectrometry
Metabolism
Statistical methods
Biomarker models
Human metabolomics
Metabolic profiling
Partial least-squares discriminant analysis (PLS-DA)
Plasmas
article
discriminant analysis
fat intake
human
human tissue
information processing
lean body weight
liquid chromatography
mass spectrometry
metabolomics
obesity
plasma
regression analysis
statistical analysis
test meal
univariate analysis
validation study
Chromatography, Liquid
Data Interpretation, Statistical
Dietary Fats
Europe
Humans
Least-Squares Analysis
Lipids
Mass Spectrometry
Obesity
Postprandial Period
To reference this document use:
http://resolver.tudelft.nl/uuid:ab0e2f5a-e697-4ea3-b706-cde024ebd656
DOI
https://doi.org/10.1021/ac051495j
TNO identifier
239091
ISSN
0003-2700
Source
Analytical Chemistry, 78 (2), 567-574
Document type
article