Christoph Steinbeck from the European Bioinformatics Institute discusses developing efficient infrastructure, standards, and data flow for metabolomics. Metabolomics measures small molecule metabolites in organisms and generates large amounts of data. The MetaboLights database was created to share metabolomics data openly. It is growing rapidly with a doubling time of 3 months for metabolomics data. Efforts are underway to build standardized reference data through projects like COSMOS and MetabolomeXchange. While genomes of thousands of species have been sequenced, far fewer complete metabolomes exist. The talk advocates for focused efforts to map metabolites and build quantitative models of well-studied model organisms' metabolomes.

1. Developing an Efficient
Infrastructure, Standards and
Data-Flow for Metabolomics
Christoph Steinbeck
European Bioinformatics Institute
(EMBL-EBI)

2. Developing an Efficient
Infrastructure, Standards and
Data-Flow for Metabolomics
Christoph Steinbeck
European Bioinformatics Institute
(EMBL-EBI)
Slides on
http://www.slideshare.net/csteinbeck

3. The
European Bioinformatics Institute
(EBI)

4. The
European Bioinformatics Institute
(EBI)

5. The
European Bioinformatics Institute
(EBI)

6. The
European Bioinformatics Institute
(EBI)

7. The
European
Molecular
Biology
Laboratory
(EMBL)
A basic research
institute funded by
public research
monies from 20
member states.

8. Post Genomic Era
Christoph Steinbeck
European Bioinformatics Institute
(EMBL-EBI)
[O]ur understanding of the human genome has
changed in the most fundamental ways.The
small number of genes -- some 30,000 --
supports the notion that we are not hard
wired.We now know the notion that one gene
leads to one protein, and perhaps one disease,
is false.
CraigVenter, June 2001

9. Understanding Phenotypes

10. Nutrition
Exercise
Disease
Age
Drugs
Environment
Phenome/
Exposome

11. Reaction times following
external change
• Genetics (decades, centuries…)
• Epigenetics (days, month, years,…)
• Gene Expression (hours)
• Metabolism (seconds)

12. The Metabolome
is the most accessible and
dynamically changing
Molecular Phenotype

13. Metabolites:
Small molecules in biological organisms

14. Metabolomics
Measures occurrence and
concentrations of many
small molecules
(metabolites) in an organism
at once.

15. Nuclear Magnetic Resonance
(NMR)
Mass Spec
Metabolomics uses a wide-range of
analytical techniques

16. Phenome Centres popping
up all over the world
• London
• Birmingham
• Shanghai
• NIH RCMRCs
• …

18. > 100,000 patient samples / year
> Several PetaBytes/year
=> ExaBytes of human data at
moderate scale-up

19. How do you make sense
of all that data?

20. Share them
-
Free and Open

21. MetaboLights
http://www.ebi.ac.uk/metabolights
open-access, cross-species, cross-application,
long-term supported
Salek, R.M., Haug, K. and Steinbeck, C. (2013) Dissemination of metabolomics results: role of MetaboLights and COSMOS. Gigascience, 2:8.

22. MetaboLights Database
Experimental Repository
Reference Layer
Chemistry Spectroscopy Biology
AnalysisTools
Primary Literature
Primary data and Meta-Data, Spectra, Protocols, Synopses, ...

24. www.ebi.ac.uk/metabolights
(metabolights.org, metabolights.eu)

25. www.ebi.ac.uk/metabolights
(metabolights.org, metabolights.eu)

26. Data growth in EBI data repositories

27. Data growth in EBI data repositories
3-month
doubling time
for
Metabolomics

28. Data growth in EBI data repositories
3-month
doubling time
for
Metabolomics
MetaboLights is now
the recommended
repository
for the Nature journals,
EMBO journal, PLOS
journals, Metabolomics
Journal and others

29. Sansone,… Steinbeck et al. (2012)
Toward interoperable bioscience data.
Nature Genetics, 44, 121–126.

30. Sansone,… Steinbeck et al. (2012)
Toward interoperable bioscience data.
Nature Genetics, 44, 121–126.
ControlledVocabularies
Ontologies

31. Sansone,… Steinbeck et al. (2012)
Toward interoperable bioscience data.
Nature Genetics, 44, 121–126.
ControlledVocabularies
Ontologies
Minimum Information Standards

33. ControlledVocabularies
Ontologies

34. ControlledVocabularies
Ontologies

39. Global Standards
and
Data Exchange
in
Metabolomics

40. COSMOS
COrdination of Standards in MetabolOmicS
European FP7 coordination
action coordinated by us at
EMBL-EBI, Hinxton,
Cambridge
• Create missing standards & formats
• Define workflows for dissemination
• Create world-wide data network

41. MetabolomeXchange 2014
• Global network for exchange and
discoverability of metabolomics data
• Includes study as well as reference data

44. The MetaboLights
Reference Layer

46. •8.7 mio eukaryotic species on earth (+- 1.3mio)

47. •8.7 mio eukaryotic species on earth (+- 1.3mio)
•1.2 mio species identified and classified

48. •8.7 mio eukaryotic species on earth (+- 1.3mio)
•1.2 mio species identified and classified
•3000 - 4000 complete species genomes sequenced

49. •8.7 mio eukaryotic species on earth (+- 1.3mio)
•1.2 mio species identified and classified
•3000 - 4000 complete species genomes sequenced

50. •8.7 mio eukaryotic species on earth (+- 1.3mio)
•1.2 mio species identified and classified
•3000 - 4000 complete species genomes sequenced
What about completed metabolomes?

51. •8.7 mio eukaryotic species on earth (+- 1.3mio)
•1.2 mio species identified and classified
•3000 - 4000 complete species genomes sequenced
What about completed metabolomes?

52. Typical total ion chromatogram of serum from a healthy subject.
Psychogios N, Hau DD, Peng J, Guo AC, Mandal R, et al. (2011) The Human Serum Metabolome. PLoS ONE 6(2): e16957. doi:10.1371/
journal.pone.0016957
http://journals.plos.org/plosone/article?id=info:doi/10.1371/journal.pone.0016957

53. There are known knowns; there are things we know
we know.
We also know there are known unknowns; that is to
say, we know there are some things we do not know.
But there are also unknown unknowns – the ones we
don’t know we don’t know.
—United States Secretary of Defense,
Donald Rumsfeld

54. Building upon extensive genomics research, we argue that the time is
now right to focus intensively on model organism metabolomes. We
propose a grand challenge for metabolomics studies of model
organisms: to identify and map all metabolites onto metabolic
pathways, to develop quantitative metabolic models for model
organisms, and to relate organism metabolic pathways within the
context of evolutionary metabolomics, i.e., phylometabolomics. These
efforts should focus on a series of established model organisms in
microbial, animal and plant research.
Metabolites. 2016 Feb 15;6(1)

55. Species Metabolomes are
being assembled on the fly
right now through data
sharing in Metabolomics

56. Repository Entry

57. Repository Entry

58. Reference Layer

62. 7 most annotated metabolomes
in MetaboLights

63. 2013
2014
2015
2016

65. Funding and Collaborators
UK Research Councils (BBSRC, MRC)
European Commission

67. Slides on
http://www.slideshare.net/csteinbeck

68. Metabolights-help@ebi.ac.uk
Thank you!