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Bayesian independent component analysis recovers pathway signatures from blood metabolomics data.
J. Proteome Res. 11, 4120-4131 (2012)
Interpreting the complex interplay of metabolites in heterogeneous biosamples still poses a challenging task. In this study, we propose independent component analysis (ICA) as a multivariate analysis tool for the interpretation of large-scale metabolomics data. In particular, we employ a Bayesian ICA method based on a mean-field approach, which allows us to statistically infer the number of independent components to be reconstructed. The advantage of ICA over correlation-based methods like principal component analysis (PCA) is the utilization of higher order statistical dependencies, which not only yield additional information but also allow a more meaningful representation of the data with fewer components. We performed the described ICA approach on a large-scale metabolomics data set of human serum samples, comprising a total of 1764 study probands with 218 measured metabolites. Inspecting the source matrix of statistically independent metabolite profiles using a weighted enrichment algorithm, we observe strong enrichment of specific metabolic pathways in all components. This includes signatures from amino acid metabolism, energy-related processes, carbohydrate metabolism, and lipid metabolism. Our results imply that the human blood metabolome is composed of a distinct set of overlaying, statistically independent signals. ICA furthermore produces a mixing matrix, describing the strength of each independent component for each of the study probands. Correlating these values with plasma high-density lipoprotein (HDL) levels, we establish a novel association between HDL plasma levels and the branched-chain amino acid pathway. We conclude that the Bayesian ICA methodology has the power and flexibility to replace many of the nowadays common PCA and clustering-based analyses common in the research field.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
metabolomics; independent component analysis; Bayesian; systems biology; bioinformatics; blood serum; population cohorts; Expression Profiles; Fmri Data; Disease; Classification; Progression; Obesity
ISSN (print) / ISBN
1535-3893
e-ISSN
1535-3907
Journal
Journal of Proteome Research
Quellenangaben
Volume: 11,
Issue: 8,
Pages: 4120-4131
Publisher
American Chemical Society (ACS)
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Bioinformatics and Systems Biology (IBIS)
Molekulare Endokrinologie und Metabolismus (MEM)
Research Unit Molecular Epidemiology (AME)
Institute of Experimental Genetics (IEG)
Molekulare Endokrinologie und Metabolismus (MEM)
Research Unit Molecular Epidemiology (AME)
Institute of Experimental Genetics (IEG)