Exploring Human Metabolites Using the Human Metabolome Database
互联网
1609
- Abstract
- Table of Contents
- Figures
- Literature Cited
Abstract
The Human Metabolome Database (HMDB) is a Web?based bioinformatic/cheminformatic resource with detailed information about human metabolites and metabolic enzymes. It can be used for fields of study including metabolomics, biochemistry, clinical chemistry, biomarker discovery, medicine, nutrition, and general education. In addition to its comprehensive literature?derived data, the HMDB contains an extensive collection of experimental metabolite concentration data for plasma, urine, CSF, and/or other biofluids The HMDB is fully searchable, with many tools for viewing, sorting and extracting metabolite names, chemical structures, biofluid concentrations, enzymes, genes, NMR or MS spectra, and disease information. Each metabolite entry in the HMDB contains an average of 90 separate data fields including a comprehensive compound description, names and synonyms, chemical structure information, physico?chemical data, reference NMR and MS spectra, normal and abnormal biofluid concentrations, tissue locations, disease associations, pathway information, enzyme data, gene sequence data, and SNP and mutation data, as well as extensive links to images, references and other public databases. Curr. Protoc. Bioinform. 25:14.8.1?14.8.45. © 2009 by John Wiley & Sons, Inc.
Keywords: Database; metabolomics; bioinformatics; cheminformatics; biochemistry; genomics; proteomics; systems biology; pathways; spectra
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online LibraryTable of Contents
- Introduction
- Basic Protocol 1: Navigating the Human Metabolome Database Web Site
- Basic Protocol 2: Chemical Structure Similarity Searching
- Basic Protocol 3: Metabolite Identification via Spectral Matching
- Guidelines for Understanding Results
- Commentary
- Literature Cited
- Figures
- Tables
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online LibraryMaterials
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online LibraryFigures
-
Figure 14.8.1 A screen shot of the HMDB home page. At the top of the page is a menu bar (light gray) with fourteen clickable menu choices (in black). This menu bar allows users to take advantage of the HMDB's rich selection of browsing and searching utilities. Below the menu bar, information about how to use, contact, and reference the HMDB are provided. View Image -
Figure 14.8.2 A screen shot showing the HMDB search results for the word histidine. The HMDB accession numbers on the left side of the table are hyperlinked. Each accession number corresponds to a human metabolite in the database. View Image -
Figure 14.8.3 A screen shot of the MetaboCard for 1‐methylhistidine. View Image -
Figure 14.8.4 A 2‐D image of the structure of 1‐methylhistidine as displayed using the ChemSketch Java applet. The image may be manipulated for different display purposes. View Image -
Figure 14.8.5 An image of the 3‐D structure of 1‐methylhistidine as displayed using the WebMol Java applet. Users may manipulate the image for better viewing or further analysis. View Image -
Figure 14.8.6 An image of the 2‐D HSQC NMR spectrum and peak list for the metabolite 1‐methylhistidine. View Image -
Figure 14.8.7 An image of the MS/MS spectrum at low energy for the metabolite 1‐methylhistidine. View Image -
Figure 14.8.8 Details of the SNP (single nucleotide polymorphism) metabolizing enzyme information contained in the MetaboCard for 1‐methylhistidine. View Image -
Figure 14.8.9 A screen shot of the HMDB Browser. Note the tabular format and the sorting and display options at the top of the Browser page. View Image -
Figure 14.8.10 A screen shot of how the HMDB Browser page should appear when sorting by Common Name and displaying 200 metabolites per page. View Image -
Figure 14.8.11 Here is the result that was obtained with the Chemical Class Browser example (amino acids, display 200 metabolites per page). View Image -
Figure 14.8.12 1‐methylhistidine appears in five different biofluids. This result was obtained using a search for this particular metabolite in different biofluids from the Biofluid Browser page. View Image -
Figure 14.8.13 Restricting the search to metabolites from gallbladder bile with associated disorders limits the number of metabolites to a total of five. View Image -
Figure 14.8.14 In this example of the HMDB Tissue Browser, only metabolites from the thyroid are displayed. View Image -
Figure 14.8.15 In this example of the HMDB TextQuery Tool, only metabolites that contain text with the word obesity are displayed. View Image -
Figure 14.8.16 The HMDB Data Extractor can be used to build complex queries as shown here. View Image -
Figure 14.8.17 The HMDB Download page provides access to many large, downloadable text files containing much of the HMDB's content. View Image -
Figure 14.8.18 Near the bottom of the HMDB Download page, up‐to‐date statistics about the HMDB downloadable content is provided. View Image -
Figure 14.8.19 In this particular view of the HMDB ChemQuery home page, the chemical structure drawing applet window is shown. View Image -
Figure 14.8.20 A variety of chemical structure templates are available to reduce some of the manual drawing requirements. View Image -
Figure 14.8.21 At this stage of the chemical structure drawing exercise, we have managed to draw a benzene ring. View Image -
Figure 14.8.22 Our dopamine drawing is beginning to take shape. At this point, we have added two oxygens to the benzene carbons at positions 5 and 6. View Image -
Figure 14.8.23 At this stage, the completed dopamine drawing is shown. View Image -
Figure 14.8.24 The MOL file text is automatically copied to the window below the CONVERT TO MOL FILE button. View Image -
Figure 14.8.25 Here is the chemical similar search result obtained for our hand‐drawn example. View Image -
Figure 14.8.26 The Show Similar Structure(s) button appears at the top right of each MetaboCard in the HMDB. View Image -
Figure 14.8.27 Here are the results obtained using the Show Similar Structure(s) button from the dopamine MetaboCard. View Image -
Figure 14.8.28 The spectral search pages (NMR, MS/MS, and GC‐MS) include a convenient drop‐down menu that allows users to search by Common Name, Synonyms, Chemical Formula, Molecular Weight, or respective peak list. View Image -
Figure 14.8.29 The NMR Search page allows users to search for a variety of NMR spectral types (1D 1 H, 1D 13 C, 2D HSQC, and 2D TOCSY). View Image -
Figure 14.8.30 As you scroll down on the MetaboCard for 1‐methylhistidine, the Experimental 1 H NMR Spectrum field will appear as shown. View Image -
Figure 14.8.31 Here is the Experimental 1 H NMR Spectrum for 1‐methylhistidine. View Image -
Figure 14.8.32 Here is the Table of Peaks for 1‐methylhistidine. View Image -
Figure 14.8.33 The completed chemical shift library query data for 1‐methylhistidine should appear as shown. View Image -
Figure 14.8.34 Here is the results table for the 1D 1 H NMR search using the peak list for 1‐methylhistidine. View Image -
Figure 14.8.35 For the multiple compound identification example, the NMR Search window should appear as shown. View Image -
Figure 14.8.36 Of the five hits that appear in the results table, the top three represent the three compounds that make up the mixture of compounds. View Image -
Figure 14.8.37 The MS Search page can be used to look for metabolites with matching molecular weight. View Image -
Figure 14.8.38 The MS Search results should appear as a four‐column table with Rank, HMDB ID, Name, and Monoisotopic Molecular Weight. View Image -
Figure 14.8.39 The MS/MS Search page should appear as shown with all the fields as default settings except for the ionization mode and the Search By pull‐down menu set at MS/MS Peaklist Data. View Image -
Figure 14.8.40 The MS/MS Search results appear at the bottom of the MS/MS Search page as an eight‐column table. View Image -
Figure 14.8.41 The filled out GC/MS Search page for L ‐lactic acid should appear as shown. View Image -
Figure 14.8.42 The GC/MS Results should appear in a multicolumn table below the query form. View Image
Videos
Literature Cited
| Ausloos, P., Clifton, C.L., Lias, S.G., Mikaya, A.I., Stein, S.E., Tchekhovskoi, D.V., Sparkman, O.D., Zaikin, V., and Zhu, D. 1999. The critical evaluation of a comprehensive mass spectral library. J. Am. Soc. Mass Spectrom. 10:287‐299 [Published erratum appears in J. Am. Soc. Mass Spectrom. 10:565]. | |
| Bairoch, A., Apweiler, R., Wu, C.H., Barker, W.C., Boeckmann, B., Ferro, S., Gasteiger, E., Huang, H., Lopez, R., Magrane, M., Martin, M.J., Natale, D.A., O'Donovan, C., Redaschi, N., and Yeh, L.S. 2005. The Universal Protein Resource (UniProt). Nucleic Acids Res. 33:D154‐D159. | |
| Bateman, A., Coin, L., Durbin, R., Finn, R.D., Hollich, V., Griffiths‐Jones, S., Khanna, A., Marshall, M., Moxon, S., Sonnhammer, E.L., Studholme, D.J., Yeats, C., and Eddy, S.R. 2004. The Pfam protein families database. Nucleic Acids Res. 32:D138‐D141. | |
| Brooksbank, C., Cameron, G., and Thornton, J. 2005. The European Bioinformatics Institute's data resources: Towards systems biology. Nucleic Acids Res. 33:D46‐D53. | |
| Frézal, J. 1998. Genatlas database, genes and development defects. C. R. Acad. Sci. III. 321:805‐817. | |
| Hamosh, A., Scott, A.F., Amberger, J.S., Bocchini, C.A., and McKusick, V.A. 2005. Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders. Nucleic Acids Res. 33:D514‐D517. | |
| Kanehisa, M., Goto, S., Kawashima, S., Okuno, Y., and Hattori, M. 2004. The KEGG resource for deciphering the genome. Nucleic Acids Res. 32:D277‐D280. | |
| Kopka, J., Schauer, N., Krueger, S., Birkemeyer, C., Usadel, B., Bergmüller, E., Dörmann, P., Weckwerth, W., Gibon, Y., Stitt, M., Willmitzer, L., Fernie, A.R., and Steinhauser, D. 2005. GMD@CSB.DB: The Golm Metabolome Database. Bioinformatics 21:1635‐1638. | |
| Krummenacker, M., Paley, S., Mueller, L., Yan, T., and Karp, P.D. 2005. Querying and computing with BioCyc databases. Bioinformatics 21:3454‐3455. | |
| Manber, U. and Bigot, P. 1997. USENIX Symposium on Internet Technologies and Systems (NSITS'97), Monterey, Calif., pp.231‐239. USENIX, Berkeley, Calif. | |
| Rebhan, M., Chalifa‐Caspi, V., Prilusky, J., and Lancet, D. 1998. GeneCards: A novel functional genomics compendium with automated data mining and query reformulation support. Bioinformatics 14:656‐664. | |
| Sadowski, J. and Gasteiger, J. 1993. From atoms to bonds to three‐dimensional atomic coordinates: Automatic model builders. Chem. Rev. 93:2567‐2581. | |
| Smith, C.A., O'Maille, G., Want, E.J., Qin, C., Trauger, S.A., Brandon, T.R., Custodio, D.E., Abagyan, R., and Siuzdak, G. 2005. METLIN: A metabolite mass spectral database. Ther. Drug Monit. 27:747‐751. | |
| Steinbeck, C., Krause, S., and Kuhn, S. 2003. NMRShiftDB‐constructing a free chemical information system with open‐source components. J. Chem. Inf. Comput. Sci. 43:1733‐1739. | |
| Wain, H.M., Lush, M., Ducluzeau, F., and Povey, S. 2002. Genew: The human gene nomenclature database. Nucleic Acids Res. 30:169‐171. | |
| Walther, D. 1997. WebMol—a Java‐based PDB viewer. Trends Biochem. Sci. 22:274‐275. | |
| Weininger, D. 1988. SMILES 1. Introduction and encoding rules. J. Chem. Inf. Comput. Sci. 28:31‐38. | |
| Wheeler, D.L., Barrett, T., Benson, D.A., Bryant, S.H., Canese, K., Church, D.M., DiCuccio, M., Edgar, R., Federhen, S., Helmberg, W., Kenton, D.L., Khovayko, O., Lipman, D.J., Madden, T.L., Maglott, D.R., Ostell, J., Pontius, J.U., Pruitt, K.D., Schuler, G.D., Schriml, L.M., Sequeira, E., Sherry, S.T., Sirotkin, K., Starchenko, G., Suzek, T.O., Tatusov, R., Tatusova, T.A., Wagner, L., and Yaschenko, E. 2005. Database resources of the National Center for Biotechnology Information. Nucleic Acids Res. 33:D39‐D45. | |
| Wishart, D.S. 2007. Current progress in computational metabolomics. Brief. Bioinform. 8:279‐293. | |
| Wishart, D.S., Yang, R., Arndt, D., Tang, P., and Cruz, J. 2005. Dynamic cellular automata: An alternative approach to cellular simulation. In Silico Biol. 5:139‐161. | |
| Wishart, D.S., Knox, C., Guo, A., Shrivastava, S., Hassanali, M., Stothard, P., and Woolsey, J. 2006. DrugBank: A comprehensive resource for in silico drug discovery and exploration. Nucleic Acids Res. 34:D668‐D672. | |
| Wishart, D.S., Tzur, D., Knox, C., Eisner, R., Guo, A.C., Young, N., Cheng, D., Jewell, K., Arndt, D., Sawhney, S., Fung, C., Nikolai, L., Lewis, M., Coutouly, M.‐A., Forsythe, I., Tang, P., Shrivastava, S., Jeroncic, K., Stothard, P., Amegbey, G., Block, D., Hau, D.D., Wagner, J., Miniaci, J., Clements, M., Gebremedhin, M., Guo, N., Zhang, Y., Duggan, G.E., MacInnis, G.D., Weljie, A.M., Dowlatabadi, R., Bamforth, F., Clive, D., Greiner, R., Li, L., Marrie, T., Sykes, B.D., Vogel, H.J., and Querengesser, L. 2007. HMDB: The Human Metabolome Database. Nucleic Acids Res. 35:D521‐D526. | |
| Internet Resources | |
| http://hmdb.ca/ | |
| Human Metabolome Database. | |
| http://www.genome.jp/dbget‐bin/www_bfind?compound | |
| KEGG Ligand Database for Chemical Compounds. | |
| http://biocyc.org/META/server.html | |
| BioCyc. | |
| http://bigg.ucsd.edu/ | |
| BiGG Database. | |
| http://en.wikipedia.org/wiki/Main_Page | |
| Wikipedia. | |
| http://metlin.scripps.edu/metabo_search.php | |
| Metlin. | |
| http://pubchem.ncbi.nlm.nih.gov/ | |
| PubChem. | |
| http://www.ebi.ac.uk/chebi/ | |
| ChEBI. | |
| http://www.acdlabs.com/products/java/sda/ | |
| ACD/Structure Drawing Applet. | |
| http://www.cmpharm.ucsf.edu/∼walther/webmol.html | |
| WebMol Web site. | |
| http://www.rcsb.org/pdb/home/home.do | |
| PDB. | |
| http://www.bmrb.wisc.edu/ | |
| BMRB. | |
| http://www.ncbi.nlm.nih.gov/pubmed/ | |
| PubMed. | |
| http://www.ncbi.nlm.nih.gov/omim/ | |
| OMIM. | |
| http://www.metagene.de/programm/tdb.prg?esp=index | |
| Metagene. | |
| http://www.genome.jp/dbget‐bin/www_bfind?pathway | |
| KEGG Pathway Database. | |
| http://wishart.biology.ualberta.ca/SimCell/ | |
| SimCell. | |
| http://www.ncbi.nlm.nih.gov/Genbank/ | |
| GenBank. | |
| http://expasy.org/sprot/ | |
| Swiss‐Prot. | |
| http://www.geneontology.org/ | |
| Gene Ontology. | |
| http://pfam.sanger.ac.uk/ | |
| Pfam. | |
| http://www.genome.jp/dbget‐bin/www_bfind?enzyme | |
| KEGG Ligand Database for Enzyme Nomenclature. | |
| http://www.genecards.org/index.shtml | |
| GeneCards. | |
| http://www.dsi.univ‐paris5.fr/genatlas/ | |
| Genatlas. | |
| http://www.genenames.org/ | |
| HUGO Gene Nomenclature Committee (HGNC). | |
| http://www.ncbi.nlm.nih.gov/projects/SNP/ | |
| dbSNP. | |
| http://nmrshiftdb.ice.mpg.de/ | |
| NMRShiftDB. | |
| http://www.nist.gov/srd/nist1a.htm | |
| NIST Spectral Database. | |
| http://riodb01.ibase.aist.go.jp/sdbs/ | |
| Spectral Database for Organic Compounds. | |
| http://csbdb.mpimp‐golm.mpg.de/ | |
| Golm Metabolome Database. |
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library
