Post on 03-Jul-2015
description
Project-teamMAGNOMEInria Bordeaux - Sud-Ouest
JOBIM 2013, July 1-4
Metabolic Model Generalization
Anna Zhukova
Where's Wally ?
Where are missing reactions ?
(The fi gure is produced using the Tulip graph visualization tool.)
Where are missing reactions ?
(The fi gure is produced using the Tulip graph visualization tool.)
Where are missing reactions ?
(The fi gure is produced using the Tulip graph visualization tool.)
Where are missing reactions ?
MODEL1111190000
Loira et al., 2012
Metabolic Network of Y. lipolytica
(peroxisome)
(53 - 6) reactions
(The fi gure is produced using the Tulip graph visualization tool.)
Where are missing reactions ?
(The fi gure is produced using the Tulip graph visualization tool.)
3-hydroxyacyl dehydrase ! Not that easy ?
(The fi gure is produced using the Tulip graph visualization tool.)
Model inference and refinement
Let's generalize !
(The fi gure is produced using the Tulip graph visualization tool.)
Let's generalize : ubiquitous species !
(The fi gure is produced using the Tulip graph visualization tool.)
Let's generalize !
(The fi gure is produced using the Tulip graph visualization tool.)
Let's generalize : hydroxy fatty acyl-CoA !
(The fi gure is produced using the Tulip graph visualization tool.)
Let's generalize !
(The fi gure is produced using the Tulip graph visualization tool.)
Let's generalize : dehydroacyl-CoA !
(The fi gure is produced using the Tulip graph visualization tool.)
Let's generalize !
(The fi gure is produced using the Tulip graph visualization tool.)
Let's generalize : 3-hydroxyacyl dehydratase !
(The fi gure is produced using the Tulip graph visualization tool.)
Let's generalize !
(The fi gure is produced using the Tulip graph visualization tool.)
Let's factor !
(The fi gure is produced using the Tulip graph visualization tool.)
Let's improve the layout a bit...
(The fi gure is produced using the Tulip graph visualization tool.)
So, where's Wally (aka 3-hydroxyacyl-CoA dehydratase) ?
(The fi gure is produced using the Tulip graph visualization tool.)
Some technical details...
Some technical details...
M = (S, Sub, R) – model
Some technical details...
M = (S, Sub, R) – model
S = {s1, ..., s
n} – species set
/including /
Sub – ubiquitous species set
Some technical details...
M = (S, Sub, R) – model
S = {s1, ..., s
n} – species set
/including /
Sub – ubiquitous species set
R = {r1, ..., r
n} – reaction set
r = (S(react), S(prod)) – reaction/all the species are distinct (*)/
Some technical details...
M = (S, Sub, R) – model
S = {s1, ..., s
n} – species set
/including /
Sub – ubiquitous species set
R = {r1, ..., r
n} – reaction set
r = (S(react), S(prod)) – reaction/all the species are distinct (*)/
Some technical details...
M = (S, Sub, R) – model
S = {s1, ..., s
n} – species set
/including /
Sub – ubiquitous species set
R = {r1, ..., r
n} – reaction set
r = (S(react), S(prod)) – reaction/all the species are distinct (*)/
stoichiometry = 2
Some technical details...
Choose equivalence operation ~ :[s]~ = {s
i | s
i ~ s} – generalized species
[s(ub)]~ = {s(ub)} – (trivial) generalized ub. sp.
M = (S, Sub, R) – model
S = {s1, ..., s
n} – species set
/including /
Sub – ubiquitous species set
R = {r1, ..., r
n} – reaction set
r = (S(react), S(prod)) – reaction/all the species are distinct (*)/
Some technical details...
Choose equivalence operation ~ :[s]~ = {s
i | s
i ~ s} – generalized species
[s(ub)]~ = {s(ub)} – (trivial) generalized ub. sp.[r]~ = (S([react]), S([prod])) =
/all the generalized species are distinct (*)/
= {ri | r
i ~ r} – generalized reaction
M = (S, Sub, R) – model
S = {s1, ..., s
n} – species set
/including /
Sub – ubiquitous species set
R = {r1, ..., r
n} – reaction set
r = (S(react), S(prod)) – reaction/all the species are distinct (*)/
Some technical details...
Choose equivalence operation ~ :[s]~ = {s
i | s
i ~ s} – generalized species
[s(ub)]~ = {s(ub)} – (trivial) generalized ub. sp.[r]~ = (S([react]), S([prod])) =
/all the generalized species are distinct (*)/
= {ri | r
i ~ r} – generalized reaction
M = (S, Sub, R) – model
S = {s1, ..., s
n} – species set
/including /
Sub – ubiquitous species set
R = {r1, ..., r
n} – reaction set
r = (S(react), S(prod)) – reaction/all the species are distinct (*)/
Some technical details...
Choose equivalence operation ~ :[s]~ = {s
i | s
i ~ s} – generalized species
[s(ub)]~ = {s(ub)} – (trivial) generalized ub. sp.[r]~ = (S([react]), S([prod])) =
/all the generalized species are distinct (*)/
= {ri | r
i ~ r} – generalized reaction
M = (S, Sub, R) – model
S = {s1, ..., s
n} – species set
/including /
Sub – ubiquitous species set
R = {r1, ..., r
n} – reaction set
r = (S(react), S(prod)) – reaction/all the species are distinct (*)/
Some technical details...
Choose equivalence operation ~ :[s]~ = {s
i | s
i ~ s} – generalized species
[s(ub)]~ = {s(ub)} – (trivial) generalized ub. sp.[r]~ = (S([react]), S([prod])) =
/all the generalized species are distinct (*)/
= {ri | r
i ~ r} – generalized reaction
M = (S, Sub, R) – model
S = {s1, ..., s
n} – species set
/including /
Sub – ubiquitous species set
R = {r1, ..., r
n} – reaction set
r = (S(react), S(prod)) – reaction/all the species are distinct (*)/
Some technical details...
Choose equivalence operation ~ :[s]~ = {s
i | s
i ~ s} – generalized species
[s(ub)]~ = {s(ub)} – (trivial) generalized ub. sp.[r]~ = (S([react]), S([prod])) =
/all the generalized species are distinct (*)/
= {ri | r
i ~ r} – generalized reaction
M = (S, Sub, R) – model
S = {s1, ..., s
n} – species set
/including /
Sub – ubiquitous species set
R = {r1, ..., r
n} – reaction set
r = (S(react), S(prod)) – reaction/all the species are distinct (*)/
Some technical details...
Choose equivalence operation ~ :[s]~ = {s
i | s
i ~ s} – quotient species
[s(ub)]~ = {s(ub)} – (trivial) quotient ub. sp.[r]~ = (S([react]), S([prod])) =
/all the quotient species are distinct (*)/
= {ri | r
i ~ r} – quotient reaction
S/~ = {[s1], ..., [s
n]} – quotient species set
R/~ = {[r1], ..., [r
n]} – quotient reaction set
M/~ = (S/~, R/~) – generalized model
M = (S, Sub, R) – model
S = {s1, ..., s
n} – species set
/including /
Sub – ubiquitous species set
R = {r1, ..., r
n} – reaction set
r = (S(react), S(prod)) – reaction/all the species are distinct (*)/
Some technical details...
Choose equivalence operation ~ :[s]~ = {s
i | s
i ~ s} – generalized species
[s(ub)]~ = {s(ub)} – (trivial) generalized ub. sp.[r]~ = (S([react]), S([prod])) =
/all the generalized species are distinct (*)/
= {ri | r
i ~ r} – generalized reaction
S/~ = {[s1], ..., [s
n]} – generalized species set
R/~ = {[r1], ..., [r
n]} – generalized reaction set
M/~ = (S/~, R/~) – generalized model
Problem: Given a model M = (S, Sub, R), find an equivalence operation ~ that obeys the stoichiometry
preserving restriction (*), and minimizes the number of generalized reactions #R/~. Among such
equivalence operations choose the one that defines the maximal number of generalized species #S/~.
M = (S, Sub, R) – model
S = {s1, ..., s
n} – species set
/including /
Sub – ubiquitous species set
R = {r1, ..., r
n} – reaction set
r = (S(react), S(prod)) – reaction/all the species are distinct (*)/
Algorithm
Problem: Given a model M = (S, Sub, R), find an equivalence operation ~ that obeys the stoichiometry
preserving restriction (*), and minimizes the number of generalized reactions #R/~. Among such
equivalence operations choose the one that defines the maximal number of generalized species #S/~.
Algorithm
1. Define ~0
• [s(ub)]~0 = {s(ub)} – (trivial) generalized ub. sp.• [s]~0 = S\S
ub – generalized specific species
s1 ~ s
2 and do not participate in any equivalent reactions, then split [s
1]~0c
Problem: Given a model M = (S, Sub, R), find an equivalence operation ~ that obeys the stoichiometry
preserving restriction (*), and minimizes the number of generalized reactions #R/~. Among such
equivalence operations choose the one that defines the maximal number of generalized species #S/~.
Algorithm
1. Define ~0
• [s(ub)]~0 = {s(ub)} – (trivial) generalized ub. sp.• [s]~0 = S\S
ub – generalized specific species
s1 ~ s
2 and do not participate in any equivalent reactions, then split [s
1]~0c
Problem: Given a model M = (S, Sub, R), find an equivalence operation ~ that obeys the stoichiometry
preserving restriction (*), and minimizes the number of generalized reactions #R/~. Among such
equivalence operations choose the one that defines the maximal number of generalized species #S/~.
Algorithm
1. Define ~0
2. Preserve stoichiometry
Problem: Given a model M = (S, Sub, R), find an equivalence operation ~ that obeys the stoichiometry
preserving restriction (*), and minimizes the number of generalized reactions #R/~. Among such
equivalence operations choose the one that defines the maximal number of generalized species #S/~.
Algorithm
1. Define ~0
2. Preserve stoichiometry
Exact Set Cover Problem(NP-complete)
Greedy algorithm
Problem: Given a model M = (S, Sub, R), find an equivalence operation ~ that obeys the stoichiometry
preserving restriction (*), and minimizes the number of generalized reactions #R/~. Among such
equivalence operations choose the one that defines the maximal number of generalized species #S/~.
Algorithm
1. Define ~0
2. Preserve stoichiometry
Exact Set Cover Problem (NP-complete)Greedy Algorithm
s1 ~ s
2 and do not participate in any equivalent reactions, then split [s
1]~0c
Exact Set Cover Problem(NP-complete)
Greedy algorithm
Problem: Given a model M = (S, Sub, R), find an equivalence operation ~ that obeys the stoichiometry
preserving restriction (*), and minimizes the number of generalized reactions #R/~. Among such
equivalence operations choose the one that defines the maximal number of generalized species #S/~.
Algorithm
1. Define ~0
2. Preserve stoichiometry
Exact Set Cover Problem (NP-complete)Greedy Algorithm
s1 ~ s
2 and do not participate in any equivalent reactions, then split [s
1]~0c
Problem: Given a model M = (S, Sub, R), find an equivalence operation ~ that obeys the stoichiometry
preserving restriction (*), and minimizes the number of generalized reactions #R/~. Among such
equivalence operations choose the one that defines the maximal number of generalized species #S/~.
Algorithm
1. Define ~0
2. Preserve stoichiometry
Exact Set Cover Problem (NP-complete)Greedy Algorithm
s1 ~ s
2 and do not participate in any equivalent reactions, then split [s
1]~0c
Exact Set Cover Problem(NP-complete)
Greedy algorithm
Problem: Given a model M = (S, Sub, R), find an equivalence operation ~ that obeys the stoichiometry
preserving restriction (*), and minimizes the number of generalized reactions #R/~. Among such
equivalence operations choose the one that defines the maximal number of generalized species #S/~.
Algorithm
1. Define ~0
2. Preserve stoichiometry
3. Maximize generalized species numberreactions, then split [s1]~0c
Problem: Given a model M = (S, Sub, R), find an equivalence operation ~ that obeys the stoichiometry
preserving restriction (*), and minimizes the number of generalized reactions #R/~. Among such
equivalence operations choose the one that defines the maximal number of generalized species #S/~.
Algorithm
1. Define ~0
2. Preserve stoichiometry
3. Maximize generalized species numberreactions, then split [s1]~0c
Problem: Given a model M = (S, Sub, R), find an equivalence operation ~ that obeys the stoichiometry
preserving restriction (*), and minimizes the number of generalized reactions #R/~. Among such
equivalence operations choose the one that defines the maximal number of generalized species #S/~.
53 → 15
Acknowledgements
Magnome Team, Inria Bordeaux, France
David James ShermanPascal DurrensFlorian LajusWitold DyrkaRazanne Issa
Acknowledgements
Magnome Team, Inria Bordeaux, France
David James ShermanPascal DurrensFlorian LajusWitold DyrkaRazanne Issa
Center for Genome Regulation and CIRIC-InriaSantiago, Chile
Nicolás Loira
Acknowledgements
Magnome Team, Inria Bordeaux, France
David James ShermanPascal DurrensFlorian LajusWitold DyrkaRazanne Issa
Center for Genome Regulation and CIRIC-InriaSantiago, Chile
Nicolás Loira
L'institut MicalisGrignon, France
Stéphanie MichelyJean-Marc Nicaud
Acknowledgements
Magnome Team, Inria Bordeaux, France
David James ShermanPascal DurrensFlorian LajusWitold DyrkaRazanne Issa
Center for Genome Regulation and CIRIC-InriaSantiago, Chile
Nicolás Loira
L'institut MicalisGrignon, France
Stéphanie MichelyJean-Marc Nicaud
LaBRI Bordeaux, France
Antoine LambertRomain Bourqui
Acknowledgements
Magnome Team, Inria Bordeaux, France
David James ShermanPascal DurrensFlorian LajusWitold DyrkaRazanne Issa
Center for Genome Regulation and CIRIC-InriaSantiago, Chile
Nicolás Loira
L'institut MicalisGrignon, France
Stéphanie MichelyJean-Marc Nicaud
LaBRI Bordeaux, France
Antoine LambertRomain Bourqui
findwally.co.ukLondon, UK
Martin HandfordWally
Thank you!