The presentation describes the pros and cons of tools for visualisation of metabolic networks.

1. Visualisation of metabolic data
Anna Zhukova 1
1Institut Pasteur
Bioinformatics and Biostatistics Hub
C3BI, USR 3756 IP CNRS
Paris, France
March 3, 2016
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2. Metabolic modelling
Metabolic models are mathematical de-
scriptions of biochemical reactions between
molecules in a cell.
Anna Zhukova Metabolic visualisation March 3, 2016 2 / 22

3. Metabolic modelling
Metabolic models are mathematical de-
scriptions of biochemical reactions between
molecules in a cell.
Model exchange formats
[Hucka et al., 2003]
XML-like
[Lloyd et al., 2004]
XML-like
[Demir et al., 2010]
OWL ontology
Anna Zhukova Metabolic visualisation March 3, 2016 2 / 22

4. Metabolic modelling
Metabolic models are mathematical de-
scriptions of biochemical reactions between
molecules in a cell.
Model exchange formats
Anna Zhukova Metabolic visualisation March 3, 2016 2 / 22

5. Metabolic modelling
Metabolic models are mathematical de-
scriptions of biochemical reactions between
molecules in a cell.
Model exchange formats
Anna Zhukova Metabolic visualisation March 3, 2016 2 / 22

6. Metabolic modelling
Metabolic models are mathematical de-
scriptions of biochemical reactions between
molecules in a cell.
Model exchange formats
Anna Zhukova Metabolic visualisation March 3, 2016 2 / 22

7. Metabolic modelling
Metabolic models are mathematical de-
scriptions of biochemical reactions between
molecules in a cell.
Model exchange formats
Anna Zhukova Metabolic visualisation March 3, 2016 2 / 22

8. Metabolic modelling
Metabolic models are mathematical de-
scriptions of biochemical reactions between
molecules in a cell.
Model visualization formats
[Le Nov`ere et al., 2009]
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9. Metabolic modelling
Metabolic models are mathematical de-
scriptions of biochemical reactions between
molecules in a cell.
Repositories
[Li et al., 2010]
379 Models annotated with metabolic
process
[Kanehisa et al., 2012]
Pathways
[Alc´antara et al., 2012]
Reactions
Anna Zhukova Metabolic visualisation March 3, 2016 2 / 22

10. Size of metabolic models
Pathway-scale – up to hundreds of reactions
Genome-scale (GSM) – thousands of reactions
98 Bacteria, 39 Eukaryota, 6 Archaea
[systemsbiology.ucsd.edu/InSilicoOrganisms/OtherOrganisms]
E. coli [Smallbone, 2013] – 2 168 reactions
S. cerevisiae [Aung et al., 2013] – 2 352 reactions
H. sapiens [Thiele et al., 2013] – 7 440 reactions
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11. Genome-scale models are complicated
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12. Genome-scale models are complicated
Anna Zhukova Metabolic visualisation March 3, 2016 4 / 22

13. Organisation and visualisation of metabolic models
Scale-free networks: fraction of nodes with k connections P(k) ∼ k−γ
, where
typically 2 < γ < 3 [Jeong et al., 2000].
Few hub metabolites, common for most networks:
H+
, H2O, O2, phosphate, ADP, ATP, NADP, NAD+
, etc. (∼ 5%)
Anna Zhukova Metabolic visualisation March 3, 2016 5 / 22

14. Organisation and visualisation of metabolic models
Scale-free networks: fraction of nodes with k connections P(k) ∼ k−γ
, where
typically 2 < γ < 3 [Jeong et al., 2000].
Few hub metabolites, common for most networks:
H+
, H2O, O2, phosphate, ADP, ATP, NADP, NAD+
, etc. (∼ 5%)
– need to be multiplicated
Anna Zhukova Metabolic visualisation March 3, 2016 5 / 22

15. Organisation and visualisation of metabolic models
Scale-free networks: fraction of nodes with k connections P(k) ∼ k−γ
, where
typically 2 < γ < 3 [Jeong et al., 2000].
Few hub metabolites, common for most networks:
H+
, H2O, O2, phosphate, ADP, ATP, NADP, NAD+
, etc. (∼ 5%)
– need to be multiplicated
Nested compartments
mitochondrion ⊂ mitochondrion membrane ⊂ cytoplasm
Anna Zhukova Metabolic visualisation March 3, 2016 5 / 22

16. Organisation and visualisation of metabolic models
Scale-free networks: fraction of nodes with k connections P(k) ∼ k−γ
, where
typically 2 < γ < 3 [Jeong et al., 2000].
Few hub metabolites, common for most networks:
H+
, H2O, O2, phosphate, ADP, ATP, NADP, NAD+
, etc. (∼ 5%)
– need to be multiplicated
Nested compartments
mitochondrion ⊂ mitochondrion membrane ⊂ cytoplasm
– ’cellular component’ in the Gene Ontology [Ashburner et al., 2000]
Anna Zhukova Metabolic visualisation March 3, 2016 5 / 22

17. Organisation and visualisation of metabolic models
Scale-free networks: fraction of nodes with k connections P(k) ∼ k−γ
, where
typically 2 < γ < 3 [Jeong et al., 2000].
Few hub metabolites, common for most networks:
H+
, H2O, O2, phosphate, ADP, ATP, NADP, NAD+
, etc. (∼ 5%)
– need to be multiplicated
Nested compartments
mitochondrion ⊂ mitochondrion membrane ⊂ cytoplasm
– ’cellular component’ in the Gene Ontology [Ashburner et al., 2000]
Cycles/cascades..
TCA cycle
Glycolysis
Anna Zhukova Metabolic visualisation March 3, 2016 5 / 22

18. Organisation and visualisation of metabolic models
Scale-free networks: fraction of nodes with k connections P(k) ∼ k−γ
, where
typically 2 < γ < 3 [Jeong et al., 2000].
Few hub metabolites, common for most networks:
H+
, H2O, O2, phosphate, ADP, ATP, NADP, NAD+
, etc. (∼ 5%)
– need to be multiplicated
Nested compartments
mitochondrion ⊂ mitochondrion membrane ⊂ cytoplasm
– ’cellular component’ in the Gene Ontology [Ashburner et al., 2000]
Cycles/cascades..
TCA cycle – circular layout
Glycolysis – hierarchical layout
Anna Zhukova Metabolic visualisation March 3, 2016 5 / 22

19. Anna Zhukova Metabolic visualisation March 3, 2016 6 / 22

20. I wanna see a pathway!
KEGG
[Kanehisa et al., 2012]
WikiPathways
[Kutmon et al., 2015]
TCA cycle
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21. I wanna see a pathway!
KEGG
[Kanehisa et al., 2012]
WikiPathways
[Kutmon et al., 2015]
TCA cycle
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22. Anna Zhukova Metabolic visualisation March 3, 2016 8 / 22

23. I wanna see my small model!
Desktop tools
Cytoscape
[Cline et al., 2007]
CellDesigner
[Funahashi et al., 2008]
VANTED
[Rohn et al., 2012]
Web-based tools
JWS online
[Olivier and Snoep, 2004]
MetDraw
[Jensen et al., 2014]
Mimoza
[Zhukova and Sher-
man, 2015]
TCA cycle [Nazaret et al., 2008]
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24. I wanna see my small model!
Desktop tools
Cytoscape
[Cline et al., 2007]
CellDesigner
[Funahashi et al., 2008]
VANTED
[Rohn et al., 2012]
Web-based tools
JWS online
[Olivier and Snoep, 2004]
MetDraw
[Jensen et al., 2014]
Mimoza
[Zhukova and Sher-
man, 2015]
TCA cycle [Nazaret et al., 2008]
Anna Zhukova Metabolic visualisation March 3, 2016 9 / 22

25. I wanna see my small model!
Desktop tools
Cytoscape
[Cline et al., 2007]
CellDesigner
[Funahashi et al., 2008]
VANTED
[Rohn et al., 2012]
Web-based tools
JWS online
[Olivier and Snoep, 2004]
MetDraw
[Jensen et al., 2014]
Mimoza
[Zhukova and Sher-
man, 2015]
TCA cycle [Nazaret et al., 2008]
Anna Zhukova Metabolic visualisation March 3, 2016 9 / 22

26. I wanna see my small model!
Desktop tools
Cytoscape
[Cline et al., 2007]
CellDesigner
[Funahashi et al., 2008]
VANTED
[Rohn et al., 2012]
Web-based tools
JWS online
[Olivier and Snoep, 2004]
MetDraw
[Jensen et al., 2014]
Mimoza
[Zhukova and Sher-
man, 2015]
TCA cycle [Nazaret et al., 2008]
Anna Zhukova Metabolic visualisation March 3, 2016 9 / 22

27. I wanna see my small model!
Desktop tools
Cytoscape
[Cline et al., 2007]
CellDesigner
[Funahashi et al., 2008]
VANTED
[Rohn et al., 2012]
Web-based tools
JWS online
[Olivier and Snoep, 2004]
MetDraw
[Jensen et al., 2014]
Mimoza
[Zhukova and Sher-
man, 2015]
TCA cycle [Nazaret et al., 2008]
Anna Zhukova Metabolic visualisation March 3, 2016 9 / 22

28. I wanna see my small model!
Desktop tools
Cytoscape
[Cline et al., 2007]
CellDesigner
[Funahashi et al., 2008]
VANTED
[Rohn et al., 2012]
Web-based tools
JWS online
[Olivier and Snoep, 2004]
MetDraw
[Jensen et al., 2014]
Mimoza
[Zhukova and Sher-
man, 2015]
TCA cycle [Nazaret et al., 2008]
Anna Zhukova Metabolic visualisation March 3, 2016 9 / 22

29. Anna Zhukova Metabolic visualisation March 3, 2016 10 / 22

30. I wanna see my huge model! Classical approach?
Desktop tools?
CellDesigner
[Funahashi et al., 2008]
Web-based tools?
MetDraw
[Jensen et al., 2014]
S. cerevisiae [Aung et al., 2013]
Anna Zhukova Metabolic visualisation March 3, 2016 11 / 22

31. I wanna see my huge model! Classical approach?
Desktop tools?
CellDesigner
[Funahashi et al., 2008]
Web-based tools?
MetDraw
[Jensen et al., 2014]
S. cerevisiae [Aung et al., 2013]
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32. Genome-scale models are complicated
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33. Zooming User Interface (ZUI)
Zoom
geometric zoom
semantic zoom
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34. Zooming User Interface (ZUI)
Zoom
geometric zoom
semantic zoom
Anna Zhukova Metabolic visualisation March 3, 2016 13 / 22

35. Zooming User Interface (ZUI)
Zoom
geometric zoom
semantic zoom
Anna Zhukova Metabolic visualisation March 3, 2016 13 / 22

36. Zooming User Interface (ZUI)
Zoom
geometric zoom
semantic zoom
Decomposition into modules
compartments
pathways
similar elements
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37. Mimoza [mimoza.bordeaux.inria.fr]
3-levels of semantic zoom:
1 full model
2 generalized view
3 compartment view
user’s model as input
fully automatic
Anna Zhukova Metabolic visualisation March 3, 2016 14 / 22

38. Mimoza [mimoza.bordeaux.inria.fr]
3-levels of semantic zoom:
1 full model
2 generalized view
3 compartment view
user’s model as input
fully automatic
Anna Zhukova Metabolic visualisation March 3, 2016 14 / 22

39. Mimoza [mimoza.bordeaux.inria.fr]
3-levels of semantic zoom:
1 full model
2 generalized view
3 compartment view
user’s model as input
fully automatic
Anna Zhukova Metabolic visualisation March 3, 2016 14 / 22

40. Mimoza [mimoza.bordeaux.inria.fr]
3-levels of semantic zoom:
1 full model
2 generalized view
3 compartment view
user’s model as input
fully automatic
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41. NaviCell [Kuperstein et al., 2013]
• large maps of molecular interactions
:) user’s model as input
:( layout is not automatic, user has to:
1 create a map in CellDesigner
2 export as an image
3 produce intermediate views in a graphical designer
4 (optionally) split the map into submaps
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42. Anna Zhukova Metabolic visualisation March 3, 2016 17 / 22

43. Genome Projector [Arakawa et al., 2009]
• zoomable genome map with multiple views
• 320 bacterial genomes
• based on Roche Biochemical Pathway wall chart
• overlay layers to highlight organism-specific reactions
:( only geometric zooming
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44. Cellular Overview [Latendresse et al., 2011]
• maps of organisms in BioCyc [Caspi et al., 2012]
• pathway-oriented
:( no compartments
:( only geometric zooming
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45. Reactome pathway browser [Croft et al., 2013]
• manually curated pathways for 19 organisms
• pathway-oriented
:) two semantic zoom levels:
1 general representation of organism’s pathways
2 detailed pathway submaps
:) compartments
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46. Escher [Zachary et al., 2015]
• manually curated pathways for human, S.cerevisiae, and E.coli
:) user can edit layout and add data
:( only geometric zoom
:( limited selection of pathways
Anna Zhukova Metabolic visualisation March 3, 2016 21 / 22

47. And the winner is...
Manual layout
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48. And the winner is...
Manual layout ZUI
Anna Zhukova Metabolic visualisation March 3, 2016 22 / 22

49. And the winner is...
Manual layout ZUI
Thank you for your attention!
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