title: Simultaneous analysis of plasma and CSF by NMR and hierarchical models fusion.
abstract: Because cerebrospinal fluid (CSF) is the biofluid which interacts most closely with the central nervous system, it holds promise as a reporter of neurological disease, for example multiple sclerosis (MScl). To characterize the metabolomics profile of neuroinflammatory aspects of this disease we studied an animal model of MScl-experimental autoimmune/allergic encephalomyelitis (EAE). Because CSF also exchanges metabolites with blood via the blood-brain barrier, malfunctions occurring in the CNS may be reflected in the biochemical composition of blood plasma. The combination of blood plasma and CSF provides more complete information about the disease. Both biofluids can be studied by use of NMR spectroscopy. It is then necessary to perform combined analysis of the two different datasets. Mid-level data fusion was therefore applied to blood plasma and CSF datasets. First, relevant information was extracted from each biofluid dataset by use of linear support vector machine recursive feature elimination. The selected variables from each dataset were concatenated for joint analysis by partial least squares discriminant analysis (PLS-DA). The combined metabolomics information from plasma and CSF enables more efficient and reliable discrimination of the onset of EAE. Second, we introduced hierarchical models fusion, in which previously developed PLS-DA models are hierarchically combined. We show that this approach enables neuroinflamed rats (even on the day of onset) to be distinguished from either healthy or peripherally inflamed rats. Moreover, progression of EAE can be investigated because the model separates the onset and peak of the disease.
authors.affiliation: Institute for Molecules and Materials, Analytical Chemistry/ Biophysical Chemistry, Radboud University Nijmegen, Nijmegen, The Netherlands. A.Smolinska@science.ru.nl
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Smolinska
authors.forename: Joram M
authors.initials: JM
authors.lastname: Posma
authors.forename: Lionel
authors.initials: L
authors.lastname: Blanchet
authors.forename: Kirsten A M
authors.initials: KA
authors.lastname: Ampt
authors.forename: Amos
authors.initials: A
authors.lastname: Attali
authors.forename: Tinka
authors.initials: T
authors.lastname: Tuinstra
authors.forename: Theo
authors.initials: T
authors.lastname: Luider
authors.forename: Marek
authors.initials: M
authors.lastname: Doskocz
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Michiels
authors.forename: Frederic C
authors.initials: FC
authors.lastname: Girard
authors.forename: Lutgarde M C
authors.initials: LM
authors.lastname: Buydens
authors.forename: Sybren S
authors.initials: SS
authors.lastname: Wijmenga
mesh_terms: D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000097:blood / Q000134:cerebrospinal fluid; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D055432:Metabolomics; D008954:Models, Biological; D009103:Multiple Sclerosis / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D051381:Rats; D011917:Rats, Inbred Lew