Metabolic data of endosymbiontic, parasitic and free bacteria
Documentation
- Comparative analysis of the metabolic networks by organisms
- Comparative analysis of the metabolic networks by sets of organisms
- Getting the SBML files and attributes of the metabolic networks
- Getting the reaction graphs and attributes of the metabolic networks
- Getting the compound graphs and attributes of the metabolic networks
- Getting the properties of the data
- Activating the data filters in SymbioCyc
- Assignation of the reaction direction
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1. Comparative analysis of the metabolic networks by organisms
This mode allows to compare the list of pathways, reactions and compounds across the metabolic networks available in SymbioCyc.
First, click in the left menu on "Compare metabolic networks". Two modes are proposed:
- Comparative analysis by organisms
- Comparative analysis by sets of organisms
Now, you have to select three things:
- The objects you want to compare
- The filters you want to apply on the metabolic networks (see here for the documentation about filters)
- The organisms you want to compare
Let's continue with an example. We are going to compare the metabolic networks of the four bacteria of the genus Buchnera in SymbioCyc.
Please check the three boxes Pathways, Compounds and Reactions (Figure 1).
Figure 1. The selection of the objects to compare
In the following, we are going to consider that no filter has been applied.
Then, check Buchnera aphidicola APS (Acyrthosiphon pisum), Buchnera aphidicola Sg (Schizaphis graminum), Buchnera aphidicola Bp (Baizongia pistaciae) and Buchnera aphidicola Cc (Cinara cedri) in the organism table (Figure 2).
Finally, click on the "Launch the comparison" button at the bottom of the page.
Figure 2. The selection of the organisms to compare
Figure 3. Resume of the comparison query
The page is divided into three parts corresponding to the comparison of the pathways, the reactions and the compounds.
Comparison of the pathway sets
The pathway comparison generates a table. For each selected organism, a column corresponds to the pathways annotated as present in this organism and not in the other selected organisms.
The last column corresponds to the metabolic pathways common to all the selected organisms (Figure 4)
Figure 4. The table generated by the comparison of the metabolic pathways
Each cell of the table is a link to the pathway comparison mode of the BioCyc-like pages of SymbioCyc. For instance, in our example, if you click on the pathway "tetrapyrrole biosynthesis I", only annotated as present in Buchnera aphidicola APS, you obtain an overview of the metabolic pathway and the associated enzymes and genes for each organism (Figure 5).
Please refer to the Biocyc documentation to interpret this page.
Figure 5. Cross species comparison of the tetrapyrrole biosynthesis in the BioCyc-like interface.
In the first columns of the table generated by SymbioCyc, each metabolic pathway is followed by the proportion of reactions for which an enzyme is annotated in the metabolic pathway for the considered organism. For instance, Buchnera aphidicola APS contains two among the six reactions which constitute the tetrapyrrole biosynthesis pathway. Furthermore, each cell corresponding to a complete pathway is highlighted in grey. It's the case, for instance, of the sirome biosynthesis pathway in B. aphidicola APS (Figure 4).
In the last column of the table, the numbers between brackets that follow the name of each metabolic pathway common to each organism correspond to the proportion of organisms in which the pathway is complete. For instance, in none of the 4 organisms, the lipoate biosynthesis pathway is complete. On the contrary, the acetate formation pathway and the non-oxydative branch of the pentose phosphate pathway are complete in the four bacteria (Figure 4), and then are highlighted in grey.
This table is followed by an other table which summarises the comparison. The number of pathways unique to each organism and the number of pathways common to each organism are indicated. Each time, the number of complete pathways and the total number of pathways in each organism is indicated (Figure 6).
Figure 6. Resume of the pathway comparison
Comparison of the reaction sets
The comparison of the reactions generates one table by selected organism. In these tables, each line corresponds to a reaction present in one organism and absent in the others. The last table contains the reactions common to each selected organism.
Each table contains six columns:
- the BioCyc id of the reaction,
- its EC number,
- the names of the left compounds,
- the names of the right compounds,
- the enzymes that catalize the reaction,
- the metabolic pathways where the reaction occurs
Figure 7. Extract of the table of reactions present in B. aphidicola and not in the other Buchnera
Each reaction is a link to the reaction comparison page of the BioCyc-like part of SymbioCyc. For instance, if you click on the "1.8.4.8-RXN" reaction in the B. aphidicola APS reaction table (Figure 7), you obtain a table generated by the pathway-tools which compares the reaction in each selected organism (Figure 8). Please refer to the BioCyc documentation to interpret this page.
Figure 8. Comparison of the 1.8.4.8 reaction in the four Buchnera in the BioCyc-like interface of SymBioCyc
The tables of reactions unique to each organism and the tables of the common reactions are followed by a summary table which indicates, respectively, the number of unique, total reactions and common reactions (Figure 9).
Figure 9. Summary table of the reaction comparison in SymbioCyc
Comparison of the compound sets
The comparison of the compounds generates one table by selected organism. In these tables, each line corresponds to a compound present in one organism and absent in the others. The last table contains the compounds common to each selected organism.
Each table contains six columns:
- the BioCyc id of the compound
- its common name
- its molecular weight,
- the number of reactions where it is involved as substrate,
- the number of compounds where it is involved as product,
- the number of metabolic pathways where it is involved
Figure 10. Compound comparison table in SymbioCyc
Each compound id is a link to the corresponding compound page in the BioCyc-like part of SymbioCyc.
These tables are followed by a summary table which indicates for each organism the number of unique and total compounds, and the number of common compounds (Figure 11).
Figure 11. Compound comparison summary table in SymbioCyc
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2. Comparative analysis of the metabolic networks by sets of organisms
This mode allows to compare the list of pathways, reactions and compounds across selected groups of metabolic networks available in SymbioCyc. First, click in the left menu on "Compare metabolic networks". Two modes are proposed:
- Comparative analysis by organisms
- Comparative analysis by sets of organisms
Now, you have to select three things:
- The objects you want to compare
- The filters you want to apply on the metabolic networks (see here for the documentation about filters)
- The sets of organisms you want to compare
- a set with four different strains of Buchnera aphidicola,
- a set with seven different species of the genus Rickettsia,
- a set with four different species of the genus Bartonella
Figure 12. The selection of the objects to compare
In the following, we are going to consider that no filter has been applied.
The organisms are ordered according to their life style, coded by a color (see the legend here).
The two first columns correspond to the name and to the description of the organism. The following columns correspond to the six sets you can specify.
Please check in the first set the four strains of Buchnera we are interested in (Figure 13).
Figure 13. Selection of the four strains of Buchnera in the first set
Now, please check in the second set the seven species of Rickettsia (Figure 14).
Figure 14. Selection of the seven species of Rickettsia in the second set
Now, please check in the third set the four species of Bartonella (Figure 15).
Figure 15. Selection of the four species of Bartonella in the third set
Finally, click on the "Launch the comparison" button at the bottom of the page.
The page of results starts with a summary of your request (Figure 16).
Figure 16. Summary of the comparison query
The page is divided into three parts corresponding to the comparison of the pathways, the reactions and the compounds.
Comparison of the pathway sets
The pathway comparison by sets of organisms generates a table. For each set, one column represents the metabolic pathways present in each organism of the set and absent in all organisms of the other sets.
The name of each pathway is followed by the number of organisms in the set that have the complete pathway. When the pathway is complete, the background of the corresponding cell is colored in grey.
For instance, the Figure 17 represents the comparison table of our example sets. Thus, the histidine biosynthesis pathway is present and complete in each organism of the first set (the four Buchnera) and absent in all other organisms of the two other sets.
Figure 17. Comparison pathway by sets of organisms
The last column of the table contains the metabolic pathways annotated as present in every organism of the selected sets. The number between brackets which follows the name of a metabolic pathway represents the number of sets for which the metabolic pathway is complete in each organism.
Each name of metabolic pathway is a link to the cross-species comparison tool of the BioCyc-like part of SymbioCyc. Please refer to the BioCyc documentation to interpret it.
Just after this table, a summary table is printed, indicating the number of metabolic pathways unique to each set and the number of metabolic pathways common to each set (Figure 18).
Figure 18. Summary table of the comparison pathway by sets of organisms
Comparison of the reaction sets
The comparison of the reactions generates one table by selected set. Each table contains the reactions present in every organism of the set, and absent in all organisms of the other sets. The last table contains the reactions present in any organism of the selected sets.
Each table contains four columns:
- the BioCyc id of the reaction,
- its EC number,
- the names of the left compounds,
- the names of the right compounds,
Figure 19. Reaction comparaison table
The reaction comparison result ends by a summary table which contains the number of reactions unique to a set and the number of common reactions (Figure 20).
Figure 20. Reaction comparaison summary table
Comparison of the compound sets
The comparison of the compounds generates one table by selected set, containing the compounds present in every organism of one set and absent in all organisms of the other sets. The last table contains the compounds common to each selected organism.
Each table contains three columns:
- the BioCyc id of the compound
- its common name
- its molecular weight,
The Figure 21 represents the top of the table of the compounds present in every organism of the first set of our example, and absent in all organisms of the other sets.
Figure 21. Compound comparaison table
The compound comparison report ends with a summary table, as illustrated in the Figure 22.
Figure 22. Compound comparaison summary table
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3. Getting the SBML files and attributes of the metabolic networks
The sbml files use a xml format to describe metabolic networks. Please visit the sbml web page to have additional information about this format.
Please click on "SBML files" in the left menu of SymbioCyc. A table is displayed as in Figure 23.
Figure 22. The SBML download window
The top of the table corresponds to the filters applied on the metabolic data. By default, no filter is applied. Click on "Apply new filters" if you want to apply some filters. Please refer to the Section 7 to have a description of the SymbioCyc filters. In the table, the SymbioCyc organisms are ordered by their life style, each one corresponding to a color (see the legend). The two first columns correspond to the name and to a brief description of the organism. The third column is the link to the SBML file according to the applied filters. The format of this file is described here.
You can directly load the sbml file in Cytoscape. The three last columns correspond to attribute files that can be used in Cytoscape to visualise some characteristics of the network. The downloadable attributes are:
- the molecular weight of each compound,
- the pathway where occurs each compound,
- the pathway where occurs each reaction
Figure 23. A SymbioCyc sbml file of B. aphidicola APS loaded in Cytoscape. The size of a compound node is proportional to its molecular weight, loaded from the attribute file downloadable in SymbioCyc
Note that, in Cytoscape, a sbml file is drawn as a bipartite graph.
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4. Getting the reaction graphs and attributes of the metabolic network
SymbioCyc provides the reaction graphs for each metabolic network it stores. To download the reaction graph of an organism, please click on "Graphs of reactions" in the left menu of SymbioCyc. After clicking, a table is displayed as in Figure 24.
Figure 24. The reaction graph download window
The top of the table corresponds to the filters applied on the metabolic data. By default, no filter is applied. Click on "Apply new filters" if you want to apply some filters. Please refer to the Section 7 to have a description of the SymbioCyc filters.
In the table, the SymbioCyc organisms are ordered by their life style, each one corresponding to a color (see the legend).
The two first columns correspond to the name and to a brief description of the organism.
The third and fourth columns correspond to the reaction graph files according to the specified filters in two modes: directed or undirected.
In a reaction graph, the nodes are the reactions of the metabolic network, labelled by their BioCyc Id. There is an edge between two reactions when one uses a substrate produced by the other. In the undirected graph, there is only a link between two reactions. In the directed graph, two reversible reactions which share metabolites are linked by two edges.
The graph file is in the sif format, specified by Cytoscape. The format of the file is very simple and is described here. You can directly load the file in Cytoscape.
Figure 25. Reaction graph of B. aphidicola APS, with the cofactors filtered, drawn in Cytoscape. We used the pathway attribute file and the Enhanced Search Plugin to highlight in yellow the reactions involved in the glycolysis.
The last three columns of the reaction graph table correspond to the pathway attribute, substrate attribute and product attribute files. These files can be loaded into Cytoscape, allowing to visualise information about the nodes as in Figure 25.
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5. Getting the compound graphs and attributes of the metabolic network
SymbioCyc provides the compound graphs for each metabolic network it stores. To download a compound graph of an organism, please click on "Graphs of compounds" in the left menu of SymbioCyc. After clicking, a table is displayed as in Figure 26.
Figure 26. The compound graph download window
The top of the table corresponds to the filters applied on the metabolic data. By default, no filter is applied. Click on "Apply new filters" if you want to apply some filters. Please refer to the Section 7 to have a description of the SymbioCyc filters.
In the table, the SymbioCyc organisms are ordered by their life style, each one corresponding to a color (see the legend).
The two first columns correspond to the name and to a brief description of the organism.
The third and fourth columns correspond to the compound graph files according to the specified filters in two modes: directed or undirected.
In a compound graph, the nodes are the compounds of the metabolic network, labelled by their BioCyc Id. There is an edge between two compounds when one is a product of at least one reaction which uses the other as substrate. In the undirected graph, a reversible or irreversible reaction corresponds to only one edge whereas a reversible reaction corresponds to two edges in the directed graph.
The graph file is in the sif format, specified by Cytoscape. The format of the file is very simple and is described here. You can directly load the file in Cytoscape.
Figure 27. Compound graph of B. aphidicola APS, with the cofactors filtered, drawn in Cytoscape. The size of a compound node is proportional to its molecular weight, loaded from the attribute file downloadable in SymbioCyc.
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6. Getting the properties of the data
SymbioCyc provides some basic statistics about the metabolic networks it contains. Click on "Global characteristics" into the left menu of SymbioCyc. A table is displayed (Figure 28).
Figure 28. Table of the global properties of the metabolic networks in SymbioCyc
The top of the table corresponds to the filters applied on the metabolic data. By default, no filter is applied. Click on "Apply new filters" if you want to apply some filters. Please refer to the Section 7 to have a description of the SymbioCyc filters.
In the table, the SymbioCyc organisms are ordered by their life style, each one corresponding to a color (see the legend).
For each organism and depending on the selected filters, the following values are displayed:
- the number of pathways,
- the number of compounds,
- the number of enzymes,
- the number of distinct EC numbers,
- the number of reactions,
- the number of metabolic genes,
- the number of reactions with no EC number specified.
Figure 29. Frequency of the 30 most connected compounds in the complete set of reactions of Buchnera aphidicola APS
The second graphic represents the total distribution of the number of reactions where are involved the compounds, as shown in Figure 30.
Figure 30. Distribution of the proportion of compounds involved in a variable number of reactions in the complete metabolic network of Buchnera aphidicola APS
The third graphic of the pdf file represents the distribution of the proportion of reactions involved in a variable number of metabolic pathways (Figure 31).
Figure 31. Distribution of the proportion of reactions involved in a variable number of metabolic pathways in the complete metabolic network of Buchnera aphidicola APS are involved
The fourth graphic represents the distribution of the proportion of reactions implying a variable number of substrates (Figure 32).
Figure 32. Distribution of the proportion of reactions implying a variable number of substrates in the complete metabolic network of Buchnera aphidicola APS are involved
The fifth graphic represents the distribution of the proportion of reactions catalysed by a variable number of enzymes (Figure 33).
Figure 33. Distribution of the proportions of reactions catalysed by a variable number of enzymes in the complete metabolic network of Buchnera aphidicola APS are involved
The sixth graphic represents the distribution of the proportion of enzymes catalysing a variable number of reactions (Figure 34).
Figure 34. Distribution of the proportion of enzymes catalysing a variable number of reactions in the complete metabolic network of Buchnera aphidicola APS are involved
Finally, the last graphic represents the proportion of reactions of which the first digit of the EC number corresponds to one of the six main enzymatic reaction classes.
Be careful, as the metabolic networks have not been intensively curated, these basic properties are only indicative!
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7. Activating the data filters in SymbioCyc
For each of the modes in SymbioCyc, the user can apply filters on the data. The activation or disactivation of each filter is done with a menu at the bottom of each page of SymbioCyc (Figure 35).
Figure 35. Filter menu in SymbioCyc
Removing reactions involving big molecules as end products
When this filter is selected, the reactions in each metabolic network produces only small molecules, i.e. compounds that are not macromolecules like proteins or nucleic acids.
Removing the reactions that involve compounds of type class
In the Pathway-Genome databases built by the pathway-tools, some reactions involve generic metabolites, representing in fact a class of metabolites. For instance, the reaction illustrated in Figure 36 represents a generic reaction which transforms an aldehyde into an acid.
This kind of reaction may cause problems during modelling as it creates artificially disconnected subnetworks.
When this filter is activated, all the reactions involving such compounds are removed from the metabolic networks.
Getting only pathway-reactions and remove side compounds
A common problem in metabolic network modelling is to deal with the ubiquitous compounds such as ATP, Water, NADH, etc...
The first solution SymbioCyc proposes to deal with ubiquitous compounds is based on the information stored in the BioCyc-like databases. Indeed, for drawing purposes, only the primary compounds of each reaction in a metabolic pathway are stored. If the user chooses to apply this filter, only reactions annotated in pathways are kept and a compound is removed from a reaction if it is marked as side compound in each metabolic pathway where the reaction occurs.
Removing pairs of cofactors in each reaction where they occur
The second way SymbioCyc offers to deal with cofactors is to remove what corresponds to classical cofactor transformations (like ATP to ADP) in each reaction they occur.
SymbioCyc uses 57 common cofactor transformations (the list is available here). If the user activates this fitler, when a pair of cofactors and the associated subproducts are found on each side of a reaction, the involved compounds are removed from the reaction.
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8. Assignation of the reaction directions
In the sbml files, reaction graphs and compound graphs, the direction of the reaction has been assigned in the following way. When a reaction always occurs in the same direction in the metabolic pathways in MetaCyc, then it is assigned as irreversible in this direction.
