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