Targeted metabolomics and mass spectrometry.

While a great emphasis has been placed on global metabolomic analysis in recent years, the application of metabolomic style analyses to specific subsets of compounds (targeted metabolomics) also has merits in addressing biological questions in a more hypothesis-driven manner. These analyses are designed to selectively extract information regarding a group of related metabolites from the complex mixture of biomolecules present in most metabolomic samples. Furthermore, targeted metabolomics can also be applied to metabolism within macromolecules, hence furthering the systems biology impact of the analysis. This chapter describes the difference between the global metabolomics approach and the undertaking of metabolomics in a targeted manner and describes the application of this type of analysis in a number of biologically and medically relevant fields.

[1]  G. Johnson,et al.  No-observed effect levels are associated with up-regulation of MGMT following MMS exposure. , 2008, Mutation research.

[2]  Christer S. Ejsing,et al.  Global analysis of the yeast lipidome by quantitative shotgun mass spectrometry , 2009, Proceedings of the National Academy of Sciences.

[3]  R. Schlögl,et al.  Caterpillar-elicited methanol emission: a new signal in plant-herbivore interactions? , 2006, The Plant journal : for cell and molecular biology.

[4]  James A. McCloskey,et al.  The RNA modification database--1998 , 1998, Nucleic Acids Res..

[5]  J. Thome,et al.  Serum protein profiling and proteomics in autistic spectrum disorder using magnetic bead-assisted mass spectrometry , 2010, European Archives of Psychiatry and Clinical Neuroscience.

[6]  J. Sjövall.  Fifty years with bile acids and steroids in health and disease , 2004, Lipids.

[7]  R. Tuytten,et al.  Analysis of urinary nucleosides. V. Identification of urinary pyrimidine nucleosides by liquid chromatography/electrospray mass spectrometry. , 2006, Rapid communications in mass spectrometry : RCM.

[8]  Adriano Barbosa-Silva,et al.  Moving pieces in a taxonomic puzzle: venom 2D-LC/MS and data clustering analyses to infer phylogenetic relationships in some scorpions from the Buthidae family (Scorpiones). , 2006, Toxicon : official journal of the International Society on Toxinology.

[9]  K. Schram,et al.  Analysis of Urinary Nucleosides , 1994 .

[10]  R. Newton,et al.  Urinary Modified Nucleosides as Tumor Markers , 2003, Nucleosides, nucleotides & nucleic acids.

[11]  Xianlin Han,et al.  Automated lipid identification and quantification by multidimensional mass spectrometry-based shotgun lipidomics. , 2009, Analytical chemistry.

[12]  Determination of active components of Ginkgo biloba in human urine by capillary high-performance liquid chromatography/mass spectrometry with on-line column-switching purification. , 2006, Rapid communications in mass spectrometry : RCM.

[13]  R. Tuytten,et al.  Study of the mass spectrometric fragmentation of pseudouridine: comparison of fragmentation data obtained by matrix-assisted laser desorption/ionisation post-source decay, electrospray ion trap multistage mass spectrometry, and by a method utilising electrospray quadrupole time-of-flight tandem mass , 2005, Rapid communications in mass spectrometry : RCM.

[14]  Xianlin Han,et al.  Global analyses of cellular lipidomes directly from crude extracts of biological samples by ESI mass spectrometry: a bridge to lipidomics. , 2003, Journal of lipid research.

[15]  D. Kell,et al.  Metabolic profiling of serum using Ultra Performance Liquid Chromatography and the LTQ-Orbitrap mass spectrometry system. , 2008, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[16]  N. Brown,et al.  Simultaneous determination of uric acid metabolites allantoin, 6-aminouracil, and triuret in human urine using liquid chromatography-mass spectrometry. , 2009, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[17]  Mass spectrometry as a tool for the selective profiling of destruxins; their first identification in Lecanicillium longisporum. , 2009, Rapid communications in mass spectrometry : RCM.

[18]  R. Ryhage,et al.  Mass spectrometry in lipid research. , 1960, Journal of lipid research.

[19]  W. Vach,et al.  Serum protein profiling by solid phase extraction and mass spectrometry: A future diagnostics tool? , 2009, Proteomics.

[20]  E. Witters,et al.  Intriguing Mass Spectrometric Behavior of Guanosine Under Low Energy Collision-Induced Dissociation: H2O Adduct Formation and Gas-Phase Reactions in the Collision Cell , 2005, Journal of the American Society for Mass Spectrometry.

[21]  U. Hofmann,et al.  Comprehensive analysis of pyrimidine metabolism in 450 children with unspecific neurological symptoms using high–pressure liquid chromatography–electrospray ionization tandem mass spectrometry , 2005, Journal of Inherited Metabolic Disease.

[22]  J. Sass,et al.  Comprehensive detection of disorders of purine and pyrimidine metabolism by HPLC with electrospray ionization tandem mass spectrometry. , 2006, Clinical chemistry.

[23]  Kevin Gleeson,et al.  Detection of lung cancer with volatile markers in the breath. , 2003, Chest.

[24]  Roberto Romero,et al.  Metabolomics in premature labor: a novel approach to identify patients at risk for preterm delivery , 2010, The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians.

[25]  M. Viant,et al.  Identifying health impacts of exposure to copper using transcriptomics and metabolomics in a fish model. , 2010, Environmental science & technology.

[26]  D. Russell,et al.  Extraction and analysis of sterols in biological matrices by high performance liquid chromatography electrospray ionization mass spectrometry. , 2007, Methods in enzymology.

[27]  W. Nyhan,et al.  A FAMILIAL DISORDER OF URIC ACID METABOLISM AND CENTRAL NERVOUS SYSTEM FUNCTION. , 1964, The American journal of medicine.

[28]  K. Sivonen,et al.  Endotoxins associated with cyanobacteria and their removal during drinking water treatment. , 2002, Water research.

[29]  P. Limbach,et al.  Matrix-assisted laser desorption/ionization mass spectrometry screening for pseudouridine in mixtures of small RNAs by chemical derivatization, RNase digestion and signature products. , 2008, Rapid communications in mass spectrometry : RCM.

[30]  M. Lagarde,et al.  Lipidomics is emerging. , 2003, Biochimica et biophysica acta.

[31]  T. Koal,et al.  Complexity and pitfalls of mass spectrometry-based targeted metabolomics in brain research. , 2010, Analytical biochemistry.

[32]  Niki Fens,et al.  Exhaled breath profiling enables discrimination of chronic obstructive pulmonary disease and asthma. , 2009, American journal of respiratory and critical care medicine.

[33]  Colin R. Janssen,et al.  Direct and transgenerational impact on Daphnia magna of chemicals with a known effect on DNA methylation. , 2010, Comparative biochemistry and physiology. Toxicology & pharmacology : CBP.

[34]  Olaf Tietje,et al.  Volatile biomarkers of pulmonary tuberculosis in the breath. , 2007, Tuberculosis.

[35]  R. Tuytten,et al.  Analysis of urinary nucleosides. IV. Identification of urinary purine nucleosides by liquid chromatography/electrospray mass spectrometry. , 2004, Rapid communications in mass spectrometry : RCM.

[36]  J. Langridge,et al.  Gas chromatography/mass spectrometric analysis of urinary nucleosides in cancer patients; potential of modified nucleosides as tumour markers. , 1993, Rapid communications in mass spectrometry : RCM.

[37]  M. Frank,et al.  Human breath analysis: methods for sample collection and reduction of localized background effects , 2010, Analytical and bioanalytical chemistry.

[38]  Donald J L Jones,et al.  Mutagenicity of DNA adducts derived from ethylene oxide exposure in the pSP189 shuttle vector replicated in human Ad293 cells. , 2009, Mutation research.

[39]  W. Cheng,et al.  Technology development in breath microanalysis for clinical diagnosis. , 1999, The Journal of laboratory and clinical medicine.

[40]  Y. Wada,et al.  Defects in pyrimidine degradation identified by HPLC-electrospray tandem mass spectrometry of urine specimens or urine-soaked filter paper strips. , 2000, Clinical chemistry.

[41]  Eoin Fahy,et al.  A comprehensive classification system for lipids11 The evaluation of this manuscript was handled by the former Editor-in-Chief Trudy Forte. Published, JLR Papers in Press, February 16, 2005. DOI 10.1194/jlr.E400004-JLR200 , 2005, Journal of Lipid Research.

[42]  Massimo Corradi,et al.  Determination of aldehydes in exhaled breath of patients with lung cancer by means of on-fiber-derivatisation SPME-GC/MS. , 2010, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[43]  J. Rice,et al.  Mass spectra of nucleic acid derivatives. II. Guanine, adenine, and related compounds. , 1967, Journal of the American Chemical Society.

[44]  Y. Wada,et al.  Rapid screening of high-risk patients for disorders of purine and pyrimidine metabolism using HPLC-electrospray tandem mass spectrometry of liquid urine or urine-soaked filter paper strips. , 2000, Clinical chemistry.

[45]  L. Bláha,et al.  LC-MS analyses of microcystins in fish tissues overestimate toxin levels—critical comparison with LC-MS/MS , 2010, Analytical and bioanalytical chemistry.

[46]  Xianlin Han.  Multi-dimensional mass spectrometry-based shotgun lipidomics and the altered lipids at the mild cognitive impairment stage of Alzheimer's disease. , 2010, Biochimica et biophysica acta.

[47]  A. Postle,et al.  Dynamic lipidomics with stable isotope labelling. , 2009, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[48]  R. Newton,et al.  Development of a Purification Procedure for the Isolation of Nucleosides from Urine Prior to Mass Spectrometric Analysis , 2000, Nucleosides, nucleotides & nucleic acids.

[49]  M. Schrader,et al.  Composition of the peptide fraction in human blood plasma: database of circulating human peptides. , 1999, Journal of chromatography. B, Biomedical sciences and applications.

[50]  Norman Ratcliffe,et al.  Volatile organic compounds as diagnostic biomarkers in gastrointestinal and liver diseases. , 2009, Journal of gastrointestinal and liver diseases : JGLD.

[51]  Bogusław Buszewski,et al.  Human exhaled air analytics: biomarkers of diseases. , 2007, Biomedical chromatography : BMC.

[52]  A. Shevchenko,et al.  Top-down lipidomic screens by multivariate analysis of high-resolution survey mass spectra. , 2007, Analytical chemistry.

[53]  J. McCloskey,et al.  Collision-induced dissociation of uracil and its derivatives , 1994, Journal of the American Society for Mass Spectrometry.

[54]  Qing Yang,et al.  Artificial neural network classification based on high-performance liquid chromatography of urinary and serum nucleosides for the clinical diagnosis of cancer. , 2002, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[55]  Mohammed A Meetani,et al.  Antimicrobial peptides from the skin secretions of the New World frogs Lithobates capito and Lithobates warszewitschii (Ranidae) , 2009, Peptides.

[56]  Andrew Lockhart,et al.  Cerebrospinal Fluid Steroidomics: Are Bioactive Bile Acids Present in Brain?* , 2009, The Journal of Biological Chemistry.

[57]  R. Newton,et al.  Quantitative determination of major active components in Ginkgo biloba dietary supplements by liquid chromatography/mass spectrometry. , 2006, Rapid communications in mass spectrometry : RCM.

[58]  A. Niveleau,et al.  Relationship between urinary excretion of modified nucleosides and rheumatoid arthritis process. , 1997, British journal of rheumatology.

[59]  C. Dent,et al.  Xanthinuria, an inborn error (or deviation) of metabolism. , 1954, Lancet.

[60]  M. Harmsen,et al.  Characterization of foot-and-mouth disease virus antigen by surface-enhanced laser desorption ionization-time of flight-mass spectrometry in aqueous and oil-emulsion formulations. , 2010, Vaccine.

[61]  W. Griffiths.  Tandem mass spectrometry in the study of fatty acids, bile acids, and steroids. , 2003, Mass spectrometry reviews.

[62]  Stefan R. Bornstein,et al.  Top-Down Lipidomics Reveals Ether Lipid Deficiency in Blood Plasma of Hypertensive Patients , 2009, PloS one.

[63]  D. Desiderio.  Mass spectrometric analysis of neuropeptidergic systems in the human pituitary and cerebrospinal fluid. , 1999, Journal of chromatography. B, Biomedical sciences and applications.

[64]  Bo Yang,et al.  A novel method to detect seven microcystins in hard clam and corbicula fluminea by liquid chromatography-tandem mass spectrometry. , 2009, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[65]  N. Pedrini,et al.  Volatile organic compounds released by the entomopathogenic fungus Beauveria bassiana. , 2008, Microbiological research.

[66]  E. Witters,et al.  In-source CID of guanosine: Gas phase ion-molecule reactions , 2006, Journal of the American Society for Mass Spectrometry.

[67]  R. Newton,et al.  Analysis of urinary nucleosides. I. Optimisation of high performance liquid chromatography/electrospray mass spectrometry. , 2000, Rapid communications in mass spectrometry : RCM.

[68]  K. S. Do,et al.  On-line trace enrichment for the simultaneous determination of microcystins in aqueous samples using high-performance liquid chromatography with diode-array detection. , 1999, Journal of chromatography. A.

[69]  J. Luk,et al.  Enhanced Detection of Early Hepatocellular Carcinoma by Serum SELDI-TOF Proteomic Signature Combined with Alpha-Fetoprotein Marker , 2010, Annals of Surgical Oncology.

[70]  R. Newton,et al.  Fingerprint profile of Ginkgo biloba nutritional supplements by LC/ESI-MS/MS. , 2008, Phytochemistry.

[71]  D. Hoppensteadt,et al.  Inflammatory Biomarker Profiling in Elderly Patients With Acute Hip Fracture Treated With Heparins , 2010, Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis.

[72]  Rainer Cramer,et al.  Serum Peptide Profiling using MALDI Mass Spectrometry , 2007, Proteomics.

[73]  Xianlin Han,et al.  Lipid Analysis: Isolation, Separation, Identification and Lipidomic Analysis , 2010 .

[74]  S. Belman,et al.  High turnover rate of transfer RNA in tumor tissue. , 1977, Cancer research.

[75]  E. Wouters,et al.  Volatile organic compounds in exhaled breath as a diagnostic tool for asthma in children , 2009, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[76]  Eoin Fahy,et al.  Subcellular organelle lipidomics in TLR-4-activated macrophages1[S] , 2010, Journal of Lipid Research.

[77]  J. Langridge,et al.  Analysis of urinary nucleosides. III. Identification of 5'-deoxycytidine in urine of a patient with head and neck cancer. , 2003, Rapid communications in mass spectrometry : RCM.

[78]  G. Racagni,et al.  Use of microwave techniques to inactivate brain enzymes rapidly. , 1982, Methods in enzymology.

[79]  S. Rozen,et al.  Alterations in tryptophan and purine metabolism in cocaine addiction: a metabolomic study , 2009, Psychopharmacology.

[80]  K. Kuo,et al.  Patterns of urinary excretion of modified nucleosides. , 1979, Cancer research.

[81]  Lloyd D. Fricker,et al.  Quantitative Neuropeptidomics of Microwave-irradiated Mouse Brain and Pituitary* , 2005, Molecular & Cellular Proteomics.

[82]  Q. Jöbsis,et al.  Metabolomics of Volatile Organic Compounds in Cystic Fibrosis Patients and Controls , 2010, Pediatric Research.

[83]  P. Svenningsson,et al.  Peptidomics-based discovery of novel neuropeptides. , 2003, Journal of proteome research.

[84]  J. Langridge,et al.  Analysis of urinary nucleosides. II. Comparison of mass spectrometric methods for the analysis of urinary nucleosides. , 2001, Rapid communications in mass spectrometry : RCM.

[85]  J. Schellens,et al.  Liquid chromatography-tandem mass spectrometric assay for the analysis of uracil, 5,6-dihydrouracil and beta-ureidopropionic acid in urine for the measurement of the activities of the pyrimidine catabolic enzymes. , 2006, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[86]  T. A. Beek.  Chemical analysis of Ginkgo biloba leaves and extracts. , 2002 .

[87]  Stefan Laufer,et al.  Metabolic signature of breast cancer cell line MCF-7: profiling of modified nucleosides via LC-IT MS coupling , 2007, BMC Biochemistry.

[88]  Andrew Lockhart,et al.  Discovering oxysterols in plasma: a window on the metabolome. , 2008, Journal of proteome research.

[89]  U. Hofmann,et al.  Sensitive method for the quantification of urinary pyrimidine metabolites in healthy adults by gas chromatography-tandem mass spectrometry. , 2003, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[90]  J. Geoffrey Chase,et al.  Classifying algorithms for SIFT-MS technology and medical diagnosis , 2008, Comput. Methods Programs Biomed..

[91]  B. Casetta,et al.  Implementing tandem mass spectrometry as a routine tool for characterizing the complete purine and pyrimidine metabolic profile in urine samples. , 2006, Journal of mass spectrometry : JMS.

[92]  Sheng Pan,et al.  Using ‘omics’ to define pathogenesis and biomarkers of Parkinson’s disease , 2010, Expert review of neurotherapeutics.

[93]  Joachim Thiery,et al.  Standardized peptidome profiling of human cerebrospinal fluid by magnetic bead separation and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. , 2009, Journal of proteomics.

[94]  S. Narayanan,et al.  Creatinine: a review. , 1980, Clinical chemistry.

[95]  K. Schram,et al.  Urinary excretion of modified nucleosides as biological marker of RNA turnover in patients with cancer and AIDS. , 1993, Clinica chimica acta; international journal of clinical chemistry.

[96]  William J. Griffiths,et al.  Mass spectrometry: from proteomics to metabolomics and lipidomics. , 2009, Chemical Society reviews.

[97]  E. Witters,et al.  Development of an on-line SPE-LC-ESI-MS method for urinary nucleosides: hyphenation of aprotic boronic acid chromatography with hydrophilic interaction LC-ESI-MS. , 2008, Analytical chemistry.

[98]  F. Borrull,et al.  Comparative study of solvent extraction and thermal desorption methods for determining a wide range of volatile organic compounds in ambient air. , 2010, Talanta.

[99]  Ian T. Baldwin,et al.  Volatile Signaling in Plant-Plant Interactions: "Talking Trees" in the Genomics Era , 2006, Science.

[100]  M. H. Borges,et al.  Tityus serrulatus venom peptidomics: assessing venom peptide diversity. , 2008, Toxicon : official journal of the International Society on Toxinology.

[101]  A. Fornace,et al.  Radiation Metabolomics. 2. Dose- and Time-Dependent Urinary Excretion of Deaminated Purines and Pyrimidines after Sublethal Gamma-Radiation Exposure in Mice , 2009, Radiation research.

[102]  W. Nyhan.  Disorders of purine and pyrimidine metabolism. , 2005, Molecular genetics and metabolism.