Metabolomics Databases Xiuxia Du, Stephen Barnes Outline • Comprehensive metabolomics databases • Compound databases • Spectral databases • Metabolic pathway databases • Drug databases • Disease & physiology databases • Raw data databases 2 Comprehensive Metabolomics Database: HMDB 4.0 3 HMDB 4.0 • www.hmdb.ca • Contain detailed information about small molecule metabolites found in the human body. • Contain or link three kinds of data - Chemical data - Clinical data - Molecular biology/biochemistry data • Contain four additional databases - DrugBank, T3DB, SMPDB, and FooDB 4 HMDB 4.0 Wishart DS, Feunang YD, Marcu A, Guo AC, Liang K, Vazquez-Fresno R, Sajed T, Johnson D, Li C, Karu N et al: HMDB 4.0: the human metabolome database for 2018.5 Nucleic Acids Res 2018, 46(D1):D608-D617. HMDB 4.0 6 HMDB 4.0 7 HMDB 4.0 8 HMDB 4.0 9 HMDB 4.0 10 HMDB 4.0 11 HMDB 4.0 12 HMDB 4.0 13 HMDB 4.0 14 HMDB 4.0 15 16 17 18 HMDB 4.0 19 HMDB: 4.0 20 HMDB: 4.0 21 HMDB: 4.0 22 HMDB: one metabocard 23 DrugBank 24 T3DB 25 SMPDB 26 FooDB 27 Compound Databases 28 Compound databases • PubChem • ChemSpider • ChEBI • KEGG Glycan • IIMDB 29 Compound databases • PubChem • ChemSpider • ChEBI • KEGG Glycan • IIMDB 30 PubChem 31 PubChem • Statistics (July 25, 2018) 32 PubChem • Information on one compound 33 PubChem • Information on one compound 34 PubChem 35 PubChem 36 PubChem 37 PubChem 38 PubChem 39 PubChem 40 PubChem 41 ChemSpider 42 ChemSpider 43 ChemSpider 44 ChemSpider • One compound 45 46 ChemSpider • Compounds with the same molecular formula 47 ChEBI • Chemical Entities of Biological Interest 48 ChEBI • About 49 ChEBI • One compound 50 • Substructure search 51 ChEBI • One compound 52 53 Spectral Databases 54 Spectral databases • NIST 14 • METLIN • MassBank • MoNA • Gold Metabolome Database • Feign GC-MS database • HMDB • BMRB • Madison Metabolomics Consortium Database • BML-NMR • mzCloud 55 Spectral databases • NIST 17 • METLIN • MassBank • MoNA • Gold Metabolome Database • Feign GC-MS database • HMDB • BMRB • Madison Metabolomics Consortium Database • BML-NMR • mzCloud 56 NIST 17 • Electron ionization mass spectral library - 306,622 spectra of 267,376 unique compounds • MS/MS library: 652,475 spectra - 176,594 ion trap spectra for 120,346 different ions of 14,351 compounds - 475,881 collision cell spectra (QTOF and tandem quad) spectra for 39,158 different ions of 14,073 compounds 57 NIST 17 • New ways to identify unknowns - Hybrid search - Annotated recurring spectral libraries - High mass accuracy MS Interpreter 58 NIST 17 EI library 59 NIST 17 EI library • Focuses on - Drugs, metabolites, and poisons - Pesticides and fungicides - Organics present in soil, water, and air - Amino acids, di- and tai-peptides - Common sample contaminants - Common analytical derivatives of the above 60 NIST 17 MS/MS library 61 NIST 17 MS/MS library 62 NIST 17 MS/MS library • 13,045 precursor precursor ions [M+H]+, [M+2H]2+, [M+H-H2O]+, [M+H-NH3]+, [M+H-OH]+, [M+H+H2O]+, [M+NH4]+, [2M+H]+, [3M+H]+, [M+Na]+, [M-H+2Na]+, [M-2H+3Na]+, [M+K]+, [M-H+2K]+, [M-2H+3K]+, [M+Li]+, [M-H+2Li]+ • 6,001 negative precursors ions [M-H]-, [M-2H]2-, [M-H-H2O]-, [M-H-NH3]-, [M-H+H2O]-, [M-H+NH3]-, [2M-H]-, [3M-H]- 63 NIST 17 MS/MS library • MS3 and MS4 spectra of the most intense peaks in the MS2 and MS3 spectra, respectively • New precursors: - In-source fragments - [M+H-neutral]+ and [M-H-neutral]- - Fragments from the original target compound within the ESI source 64 METLIN 65 METLIN 66 METLIN: search simple advanced batch 67 METLIN 68 METLIN 69 METLIN 70 MassBank 71 MassBank 72 MassBank 73 MassBank 74 75 MassBank 76 MassBank 77 MassBank 78 MoNA 79 MoNA 80 Metabolic pathway databases • KEGG • MetaCyc • HumanCyc • BioCyc • Reactome • WikiPathways 81 Drug databases • DrugBank • Therapeutic target databases • PharmGKB • STITCH • SuperTarget 82 Disease & physiology databases • OMIM • METAGENE • OMMBID 83 Raw data databases • Metabolomics Workbench • MetaboLights 84 MetaboLights 85 MetaboLights 86 MetaboLights 87 MetaboLights 88 MetaboLights 89 MetaboLights 90 MetaboLights 91 MetaboLights 92 PubChem, NIST, and HMDB, again • In terms of unique molecular formula PubChem NIST 3,481,721 66,269 3,412,370 59,621 2,000 4,647 5,083 1 471 HMDB 10,202 based on database version in 2016 93 PubChem, NIST, and HMDB, again • In terms of unique InChi Key PubChem HMDB 91,116,605 41,887 91,101,371 15,234 26,653 based on database version in 2016 94 Thank you! 95.