The document discusses various methods and challenges for identifying compounds based on limited information such as mass, name, fingerprint, or spectral data. It describes searching public databases, calculating elemental compositions, comparing spectra, and predicting fragmentation patterns to identify molecules or narrow down candidates. Even with this information, unique identification can be difficult, and integration of additional data types may be needed.

1. Identifying toxicants and metabolites well, - Annotating in most cases Steffen Neumann Leibniz Institute of Plant Biochemistry Mass Spectrometry and Bioinformatics group [email_address]

3. You know the first name

4. You know the fingerprint

5. You know the fingerprint, but he's not in the files

6. And if nobody else has seen him ?

8. (Usually) no extra software needed

9. And obtain zillions of hits

10. Caveat: you know the monoisotopic mass, not the average mass www.msu.edu/~gallego7/MassSpect/

13. Median mass : 383

15. 3000ppm @300Da -> nominal mass

16. Hardly improvement below 10ppm: -> same elemental composition

18. Add N-rule, DBE, CH ratios, MS/MS etc. to narrow down relevant formulas ( Caveat: don't filter compounds of interest! )

19. So you can do a better search in KEGG, PubChem, ChemSpider, ChEBI, CAS, …

20. Not zillion hits, but still too many

22. Estimated Metabolites: 2.500 Human, 5.000 Arabidopsis, 200.000 Plant kingdom ( D.Strack, K.Saito ) http://fiehnlab.ucdavis.edu

24. But MS observes ions: Adduct ? Fragment ?

25. Search for these “modifications” (e.g. ARMeC, HMDB, KNApSAcK, …) doi:10.1038/nprot.2007.512

27. Manually extracted from literature

28. Java Application or simple Web Form

29. Search possible adduct modifications Metabolite 49553 entries metabolite-species pair 95077 entries last update 2010/03/04

32. Bioconductor CAMERA calculates [M] http://www.acdlabs.com/

34. Spectral libraries with reference spectra

35. GC/MS also produces nice spectra Tandem-MS and MS n in space ( QqQ, QqTOF ) or time (Orbi/Ion -trap) Molecules fragment upon collision -> CID Different MS parameters -> different spectra

37. 190.000 EI spectra 14.800 ESI spectra (all nominal mass)

38. NIST MS Search

39. Plain record format .msp

41. ESI (and EI)

42. Rich Web Interface

43. Batch Search

44. Web Services Others DBs with MS/MS: MetLin,HMDB,MMCD

46. But not really solved, actually you want to compare compounds / peptides behind spectra

47. Peak Count and its variants

48. Cosine distance

49. Absolute, relative or “ranked” intensities

51. Use ranked instead of absolute/relative intensities

52. Probability that a rank from an experimental spectrum matches a rank from a library spectrum

53. Requires training on given database

55. Model distribution(s) of (mis-) matching spectra

56. -> highest for correct compound DOI: 10.1021/ac900954d

58. evaluate QqQ (query) + QTOF (DB)

59. Oberacher: 402 cpds, 3759 spectra library (QqQ,QTOF,QLit,LIT-FT)

60. Training of scoring function -> Not as bad as expected DOI 10.1002/jms.1525

62. ACD Fragmenter, Waters, Bruker

66. Fragmentation analysis for each candidate

69. In-silico fragmentation to “explain” peaks

70. Score: #peaks and BDE

75. Determination of molecular structures using tandem MS (United States Patent 7197402)

77. log K ow (ChemSpider) -> Caveat: “If any one of your hints (m/z, RT, Fragmentation, …) is wrong, then the whole assignment is wrong.” (D. S. Richards, What is Structure Elucidation, Structure 2010, Hinckley, UK, 24 February 2010)

80. Putatively characterized compound classes

81. Unknowns (sic!) 10.1007/s11306-007-0082-2

84. Search PubChem with tandem-MS: msbi.ipb-halle.de/MetFrag/

85. Best of both worlds: MetFusion

86. Questions ?