title: 1H NMR metabonomics of plasma lipoprotein subclasses: elucidation of metabolic clustering by self-organising maps.
abstract: (1)H NMR spectra of plasma are known to provide specific information on lipoprotein subclasses in the form of complex overlapping resonances. A combination of (1)H NMR and self-organising map (SOM) analysis was applied to investigate if automated characterisation of subclass-related metabolic interactions can be achieved. To reliably assess the intrinsic capability of (1)H NMR for resolving lipoprotein subclass profiles, sum spectra representing the pure lipoprotein subclass part of actual plasma were simulated with the aid of experimentally derived model signals for 11 distinct lipoprotein subclasses. Two biochemically characteristic categories of spectra, representing normolipidaemic and metabolic syndrome status, were generated with corresponding lipoprotein subclass profiles. A set of spectra representing a metabolic pathway between the two categories was also generated. The SOM analysis, based solely on the aliphatic resonances of these simulated spectra, clearly revealed the lipoprotein subclass profiles and their changes. Comparable SOM analysis in a group of 69 experimental (1)H NMR spectra of serum samples, which according to biochemical analyses represented a wide range of lipoprotein lipid concentrations, corroborated the findings based on the simulated data. Interestingly, the choline-N(CH(3))(3) region seems to provide more resolved clustering of lipoprotein subclasses in the SOM analyses than the methyl-CH(3) region commonly used for subclass quantification. The results illustrate the inherent suitability of (1)H NMR metabonomics for automated studies of lipoprotein subclass-related metabolism and demonstrate the power of SOM analysis in an extensive and representative case of (1)H NMR metabonomics.
authors.affiliation: Laboratory of Computational Engineering, Systems Biology and Bioinformation Technology, Helsinki University of Technology, Finland.
authors.forename: Teemu
authors.initials: T
authors.lastname: Suna
authors.forename: Aino
authors.initials: A
authors.lastname: Salminen
authors.forename: Pasi
authors.initials: P
authors.lastname: Soininen
authors.forename: Reino
authors.initials: R
authors.lastname: Laatikainen
authors.forename: Petri
authors.initials: P
authors.lastname: Ingman
authors.forename: Sanna
authors.initials: S
authors.lastname: Mäkelä
authors.forename: Markku J
authors.initials: MJ
authors.lastname: Savolainen
authors.forename: Minna L
authors.initials: ML
authors.lastname: Hannuksela
authors.forename: Matti
authors.initials: M
authors.lastname: Jauhiainen
authors.forename: Marja-Riitta
authors.initials: MR
authors.lastname: Taskinen
authors.forename: Kimmo
authors.initials: K
authors.lastname: Kaski
authors.forename: Mika
authors.initials: M
authors.lastname: Ala-Korpela
mesh_terms: D002794:Choline / Q000378:metabolism; D006801:Humans; D008074:Lipoproteins / Q000097:blood* / Q000145:classification* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D011522:Protons
chemical_list: D008074:Lipoproteins; D011522:Protons; D002794:Choline