title: FragClust and TestClust, two informatics tools for chemical structure hierarchical clustering analysis applied to lipidomics. The example of Alzheimer's disease.
abstract: Lipidomic analysis is able to measure simultaneously thousands of compounds belonging to a few lipid classes. In each lipid class, compounds differ only by the acyl radical, ranging between C10:0 (capric acid) and C24:0 (lignoceric acid). Although some metabolites have a peculiar pathological role, more often compounds belonging to a single lipid class exert the same biological effect. Here, we present a lipidomics workflow that extracts the tandem mass spectrometry data from individual files and uses them to group compounds into structurally homogeneous clusters by chemical structure hierarchical clustering analysis (CHCA). The case-to-control peak area ratios of the metabolites are then analyzed within clusters. We created two freely available applications to assist the workflow: FragClust to generate the tables to be subjected to CHCA, and TestClust to perform statistical analysis on clustered data. We used the lipidomics data from the plasma of Alzheimer's disease (AD) patients in comparison with healthy controls to test the workflow. To date, the search for plasma biomarkers in AD has not provided reliable results. This article shows that the workflow is helpful to understand the behavior of whole lipid classes in plasma of AD patients.
authors.affiliation: Department of Biopatologia e Biotecnologie Mediche e Forensi (DiBiMEF), AOUP ''Paolo Giaccone'' University of Palermo, Palermo, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Di Gaudio
authors.affiliation: Mass Spectrometry Laboratory for Clinical Risk and Quality Control, A.O.U.P. "P. Giaccone", University of Palermo, Palermo, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Indelicato
authors.affiliation: Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, Palermo, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Monastero
authors.affiliation: Department of Biomedicine Internal Medicine and Medical Specialties, Division of Internal Medicine and Genetic Dyslipidemias, University of Palermo, Palermo, Italy.
authors.forename: Grazia Ida
authors.initials: GI
authors.lastname: Altieri
authors.affiliation: Department of Biomedicine Internal Medicine and Medical Specialties, Division of Internal Medicine and Genetic Dyslipidemias, University of Palermo, Palermo, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Fayer
authors.affiliation: Department of Biomedicine Internal Medicine and Medical Specialties, Division of Internal Medicine and Genetic Dyslipidemias, University of Palermo, Palermo, Italy.
authors.forename: Ornella
authors.initials: O
authors.lastname: Palesano
authors.affiliation: Mass Spectrometry Laboratory for Clinical Risk and Quality Control, A.O.U.P. "P. Giaccone", University of Palermo, Palermo, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Fontana
authors.affiliation: Department of Biomedicine Internal Medicine and Medical Specialties, Division of Internal Medicine and Genetic Dyslipidemias, University of Palermo, Palermo, Italy.
authors.forename: Angelo B
authors.initials: AB
authors.lastname: Cefalù
authors.affiliation: Department of Biomedicine Internal Medicine and Medical Specialties, Division of Internal Medicine and Genetic Dyslipidemias, University of Palermo, Palermo, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Greco
authors.affiliation: Department of Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), University of Palermo, Palermo, Italy.
authors.forename: David
authors.initials: D
authors.lastname: Bongiorno
authors.affiliation: Department of Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), University of Palermo, Palermo, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Indelicato
authors.affiliation: Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, Palermo, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Aronica
authors.affiliation: Department of Biomedicine Internal Medicine and Medical Specialties, Division of Internal Medicine and Genetic Dyslipidemias, University of Palermo, Palermo, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Noto
authors.affiliation: Department of Biomedicine Internal Medicine and Medical Specialties, Division of Internal Medicine and Genetic Dyslipidemias, University of Palermo, Palermo, Italy. maurizio.averna@unipa.it.
authors.forename: Maurizio R
authors.initials: MR
authors.lastname: Averna
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D015394:Molecular Structure; D053719:Tandem Mass Spectrometry
chemical_list: D008055:Lipids
keywords: Ceramides; Data mining; High-resolution mass spectrometry; Phospholipids; Triglycerides