Leccin 9

Mtodos de reconstruccin de redes

metablicas
Curso
Aproximacin al estudio de clula
mnima desde la Biologa de
Sistemas
Montevideo 6-10 diciembre 2010

Federico Morn
Departamento de Bioqmica y Biologa Molecular
Universidad Complutense madrid, Espaa
 Metabolic reconstruction

Two main approaches:

Reconstruction using the knowledge of
networks from different databases
Reconstruction using mathematical tools
like graph theory and/or network
stoichiometric analysis.
Reconstruccin por comparacin
 Stoichiometric and constraint
based analysis
Mass balance in the reaction network
Steady state
Graph theory
Nodes (metabolites) and connections (reactions)
Matrix of connections
Convex analysis
Null Space
 Tools-4-Metatool
Online suite of web-tools to process
stoichiometric network analysis data from
METATOOL
Metatool
Computational tool that performs the basic
operations for a full stoichiometric analysis
bbm1.ucm.es/t4m
 Tools 4 Metatool
http://bbm1.ucm.es/t4m

CheckMIn

Metatool Input

Compare
Cobra2Metatool
Metatool Output Metatool Output
Specie 1 Specie 2

Metatool CBasis2Metatool

Compara ComparaSub ComparaEM

Cobra file (SBML)

Metatool Output

List of reactions
Analysis

MDigraph MetaMatrixTXT CBGraph EMGraph SortEModes

KEGG info file

 MDigraph

Draws bipartite directed graphs of Metatool metabolic network, its
subsets and the subsets' pathways.

Given a kegg info file it links enzyme's nodes to Kegg.

Mdigraph output for Glycolysis + Pentose shunt. Graph of complete metabolic network.
Mdigraph Subset graph

Mdigraph output for Glycolysis + Pentose shunt. Subset graph, subset 4 subgraph
and link to KEGG information.
 MetaMatrixTXT Vectorial Output
CONVEX BASIS ELEMENTARY MODES
Visualizes the convex basis and
elementary modes of Metatool 1: 1:

output in function of subsets, in | SUB_1 | | 0 | | SUB_1 | | 3 |

vectorial or matrix format. | SUB_2 | | 0 | | SUB_2 | | 1 |

Matrix Output
| SUB_3 | | 0 | | SUB_3 | | 1 |
CONVEX BASIS
| SUB_4 | = | -1 | | SUB_4 | = | 1 |
0 0 0 -
1 1 0 0 | SUB_5 | | 1 | | SUB_5 | | 0 |

3 1 1 1 0 - | SUB_6 | | 0 | | SUB_6 | | -1 |
1 0
| SUB_7 | | 0 | | SUB_7 | | 0 |
-
2 0 1 1 0 1 1 ------------------------------ -----------------------------------
ELEMENTARY MODES 2: 2:
3 1 1 1 0 - | SUB_1 | | 3 | | SUB_1 | | -2 |
1 0
| SUB_2 | | 1 | | SUB_2 | | 0 |
-
2 0 1 1 0 1 1
| SUB_3 | | 1 | | SUB_3 | | 1 |
1 1 2 2 0 0 1
| SUB_4 | = | 1 | | SUB_4 | = | 1 |
0 2 5 5 0 1 3
| SUB_5 | | 0 | | SUB_5 | | 0 |
3 1 1 0 1 -
1 0 | SUB_6 | | -1 | | SUB_6 | | 1 |

- | SUB_7 | | 0 | | SUB_7 | | 1 |
2 output
MetaMatrixTXT 0 for Glycolysis
1 0 1 shunt. 1
+ Pentose 1 vectorial output.
Matrix and
... ...
 CBGraph

Draws bipartite directed graphs of Metatool convex basis and its pathways.

Given a kegg info file it links enzyme's nodes to Kegg.

CBGraph output for Glycolysis + Pentose shunt. Convex basis graph and subgraphs of convex bais 1 and 2.
 EMGraph

Draws bipartite directed graphs of Metatool elementary
modes and its pathways.

The user can chose the elementary modes to draw.

Given a kegg info file it links enzyme's nodes to Kegg.

EMGraph output for Glycolysis + Pentose shunt. Elementary mode graph and subgraph of elementary mode 1.
 SortEM

Sort Metatool elementery modes that contain a given metabolite (or a list of
metabolites) in a certain side of its reaction.

Side of reaction: left (reactant), right (product) or both

Search for "glc" at left.

1: length= 11, EM: 4: GPI FBA TPIA (2 GADPH) (2 PGK) (2 PGAM) (2 ENO) (2 LDH)
HK PFK (2 PK)
2: length= 12, EM: 8: GPI FBA TPIA (2 GADPH) (2 PGAM) (2 ENO) (2 LDH) (2 BPGM)
HK PFK (2 PK) (2 BPGF)
3: length= 16, EM: 3: (-2 GPI) GADPH PGK PGAM ENO LDH RPIA (2 RPE) TK TA TK2
(3 G6PD) (3 PGL) (3 PGD) HK PK
4: length= 17, EM: 7: (-2 GPI) GADPH PGAM ENO LDH BPGM RPIA (2 RPE) TK TA TK2
(3 G6PD) (3 PGL) (3 PGD) HK PK BPGF
5: length= 18, EM: 5: (2 FBA) (2 TPIA) (5 GADPH) (5 PGK) (5 PGAM) (5 ENO) (5 LDH)
RPIA (2 RPE) TK TA TK2 (3 G6PD) (3 PGL) (3 PGD) (3 HK) (2 PFK) (5 PK)
6: length= 19, EM: 9: (2 FBA) (2 TPIA) (5 GADPH) (5 PGAM) (5 ENO) (5 LDH) (5 BPGM)
RPIA (2 RPE) TK TA TK2 (3 G6PD) (3 PGL) (3 PGD) (3 HK) (2 PFK) (5 PK) (5 BPGF)
 Others tools
Compare
Compara: compares distinct Metatool outputs and shows the
identical subsets.

ComparaSub: compares distinct Metatool outputs and shows

the first output in function of the subsets of the second.

ComparaEM: compares distinct Metatool outputs and shows

the identical elementary modes.

Cbasis2Metatool: create a Metatool input file based on the

Convex Basis
Cobra2Metatool: convert a COBRA SBML file to Metatool input
CheckMIn: Checks if Metatool input is in the rigth format and if
the eznymes and metabolites were declared and used correctly.
Comparison between the production pathways for Valine of two bacterial
endosymbionts: Bucnera aphidicola of Cinara cedri (BCc) and Buchnera
aphidicola of Acyrthosiphon pisum (BAPS)

Cobra file (SBML) Cobra2Metatool Metatool Input

CBasis2Metatool Metatool Output Metatool

Metatool Input Metatool

Metatool Output

Compara ComparaSub ComparaEM

.comp .compsub .compem

 Compare
We have tested Compare in a large metabolic network
BAPS has a much complex metabolic network than BCc

We can infer those reactions that are always necessary for the
production of tryptophan and valine; and those that may be discarded
depending on the environment in which the bacteria lives.
 Comparison between the production pathways of Tryptophan
of two bacterial endosymbionts: Bucnera aphidicola of Cinara
cedri (BCc) and Buchnera aphidicola of Acyrthosiphon pisum
(BAPS)
APHIP
BAPS
Glutamine + prpp + chor + Serine

BAPS: the
endosymbiont
Pyruvate + CO2 + H2O + Glutamate + contains all necessary
ppi + g3p + genes for Tryptophan
TRYPTOPHAN TRYPTOPHAN
synthesis
TRYPTOPHAN
APHIP
BCc METASYSTEM
Glutamine + chor
Bcc: endosymbiont
TRYPTOPHAN TRYPTOPHAN has incomplete
genes for
Tryptophan
Pyruvate + Glutamate + h +
ANTHRANILATE ANTHRANILATE
production
Love UCM Biophysics Group
Systems Francisco Montero
Daniela D. Xavier
Biology Sara Vzquez