visualisation of metabolic data

Visualisation of metabolic data

Anna Zhukova 1

1Institut PasteurBioinformatics and Biostatistics Hub

C3BI, USR 3756 IP CNRSParis, France

March 3, 2016

Anna Zhukova Metabolic visualisation March 3, 2016 1 / 22

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

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

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

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

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

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

Metabolic modelling

Metabolic models are mathematical de-

scriptions of biochemical reactions between

molecules in a cell.

Model visualization formats

[Le Novere et al., 2009]

Anna Zhukova Metabolic visualisation March 3, 2016 2 / 22

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

[Alcantara et al., 2012]Reactions

Anna Zhukova Metabolic visualisation March 3, 2016 2 / 22

Size of metabolic models

Pathway-scale – up to hundreds of reactions

Genome-scale (GSM) – thousands of reactions98 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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Genome-scale models are complicated

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Genome-scale models are complicated

Anna Zhukova Metabolic visualisation March 3, 2016 4 / 22

Organisation and visualisation of metabolic models

Scale-free networks: fraction of nodes with k connections P(k) ∼ k−γ , wheretypically 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

Organisation and visualisation of metabolic models

Scale-free networks: fraction of nodes with k connections P(k) ∼ k−γ , wheretypically 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

Organisation and visualisation of metabolic models

Scale-free networks: fraction of nodes with k connections P(k) ∼ k−γ , wheretypically 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

Organisation and visualisation of metabolic models

Scale-free networks: fraction of nodes with k connections P(k) ∼ k−γ , wheretypically 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

Organisation and visualisation of metabolic models

Scale-free networks: fraction of nodes with k connections P(k) ∼ k−γ , wheretypically 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

Organisation and visualisation of metabolic models

Scale-free networks: fraction of nodes with k connections P(k) ∼ k−γ , wheretypically 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

Anna Zhukova Metabolic visualisation March 3, 2016 6 / 22

I wanna see a pathway!

KEGG[Kanehisa et al., 2012]

WikiPathways[Kutmon et al., 2015]

TCA cycle

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I wanna see a pathway!

KEGG[Kanehisa et al., 2012]

WikiPathways[Kutmon et al., 2015]

TCA cycle

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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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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

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

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

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

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

Anna Zhukova Metabolic visualisation March 3, 2016 10 / 22

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

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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Genome-scale models are complicated

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Zooming User Interface (ZUI)

Zoomgeometric zoomsemantic zoom

Decomposition into modulescompartmentspathwayssimilar elements

Anna Zhukova Metabolic visualisation March 3, 2016 13 / 22

Zooming User Interface (ZUI)

Zoomgeometric zoomsemantic zoom

Decomposition into modulescompartmentspathwayssimilar elements

Anna Zhukova Metabolic visualisation March 3, 2016 13 / 22

Zooming User Interface (ZUI)

Zoomgeometric zoomsemantic zoom

Decomposition into modulescompartmentspathwayssimilar elements

Anna Zhukova Metabolic visualisation March 3, 2016 13 / 22

Zooming User Interface (ZUI)

Zoomgeometric zoomsemantic zoom

Decomposition into modulescompartmentspathwayssimilar elements

Anna Zhukova Metabolic visualisation March 3, 2016 13 / 22

Mimoza [mimoza.bordeaux.inria.fr]

3-levels of semantic zoom:1 full model2 generalized view3 compartment view

user’s model as inputfully automatic

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Mimoza [mimoza.bordeaux.inria.fr]

3-levels of semantic zoom:1 full model2 generalized view3 compartment view

user’s model as inputfully automatic

Anna Zhukova Metabolic visualisation March 3, 2016 14 / 22

Mimoza [mimoza.bordeaux.inria.fr]

3-levels of semantic zoom:1 full model2 generalized view3 compartment view

user’s model as inputfully automatic

Anna Zhukova Metabolic visualisation March 3, 2016 14 / 22

Mimoza [mimoza.bordeaux.inria.fr]

3-levels of semantic zoom:1 full model2 generalized view3 compartment view

user’s model as inputfully automatic

Anna Zhukova Metabolic visualisation March 3, 2016 15 / 22

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 CellDesigner2 export as an image3 produce intermediate views in a graphical designer4 (optionally) split the map into submaps

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Anna Zhukova Metabolic visualisation March 3, 2016 17 / 22

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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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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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 pathways2 detailed pathway submaps

:) compartments

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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

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And the winner is...

Manual layout

ZUI

Thank you for your attention!

Anna Zhukova Metabolic visualisation March 3, 2016 22 / 22

And the winner is...

Manual layout ZUI

Thank you for your attention!

Anna Zhukova Metabolic visualisation March 3, 2016 22 / 22

And the winner is...

Manual layout ZUI

Thank you for your attention!

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