title: Integration of transcriptomics and metabonomics: improving diagnostics, biomarker identification and phenotyping in ulcerative colitis.
abstract: A systems biology approach to multi-faceted diseases has provided an opportunity to establish a holistic understanding of the processes at play. Thus, the current study merges transcriptomics and metabonomics data in order to improve diagnostics, biomarker identification and to explore the possibilities of a molecular phenotyping of ulcerative colitis (UC) patients. Biopsies were obtained from the descending colon of 43 UC patients (22 active UC and 21 quiescent UC) and 15 controls. Genome-wide gene expression analyses were performed using Affymetrix GeneChip Human Genome U133 Plus 2.0. Metabolic profiles were generated using1H Nuclear magnetic resonance spectroscopy (Bruker 600 MHz, Bruker BioSpin, Rheinstetten, Germany). Data were analyzed with the use of orthogonal-projection to latent structure-discriminant analysis and a multivariate logistic regression model fitted by lasso. Prediction performance was evaluated using nested Monte Carlo cross-validation. The prediction performance of the merged data sets and that of relative small (<20 variables) multivariate biomarker panels suggest that it is possible to discriminate between active UC, quiescent UC, and controls; between patients with or without steroid dependency, as well as between early or late disease onset. Consequently, this study demonstrates that the novel approach of integrating metabonomics and transcriptomics combines the better of the two worlds, and provides us with clinical applicable candidate biomarker panels. These combined panels improve diagnostics and more importantly also the molecular phenotyping in UC and provide insight into the pathophysiological processes at play, making optimized and personalized medication a possibility.
authors.affiliation: Department of Cellular and Molecular Medicine, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.|Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jacob Tveiten
authors.initials: JT
authors.lastname: Bjerrum
authors.affiliation: Department of Statistics, Oxford University, Oxford, UK.|State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Centre for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, The Chinese Academy of Sciences, Wuhan, People's Republic of China.
authors.forename: Mattias
authors.initials: M
authors.lastname: Rantalainen
authors.affiliation: State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Centre for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, The Chinese Academy of Sciences, Wuhan, People's Republic of China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, People's Republic of China.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cellular and Molecular Medicine, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jørgen
authors.initials: J
authors.lastname: Olsen
authors.affiliation: Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ole Haagen
authors.initials: OH
authors.lastname: Nielsen
keywords: Colonic biopsy; Gene expression profiles; Inflammatory bowel disease; Metabolic profiles; Metabolomics; NMR spectroscopy