Edit a metabolic model by adding, removing, or altering compounds, reactions, or biomass formulations.
This App is used to make changes to a metabolic model in the KBase platform. Using the menus in this App, you can: (i) add a new biomass objective function; (ii) change the stoichiometry of an existing biomass objective function in the model; (iii) add a new compounds to the model; (iv) change an existing compounds in the model; (v) add a new reaction to the model; and (vi) change an existing reaction in the model. We will describe each of these capabilities in a little more detail here.
Adding new biomass objective functions to the model
This App enables you to add new biomass objective functions to your model. The control panel for doing this enables you to specify the biomass name and its content. The name is meant to be a recognizable human readable name describing the meaning of the biomass objective function. The biomass ID is automatically assigned, with IDs number consecutively with a bio prefix (e.g. bio1, bio2 etc). When adding a biomass reaction, this tool will automatically populate the reaction with compounds based on the specified values for the DNA, RNA, protein, cell wall, lipid, cofactor, and energy components. For example, if the DNA fraction specified is greater than zero, the tool will automatically add all deoxynucleotides to the biomass reaction. All DNA, RNA, protein, cell wall, lipid, and cofactor parameters should be specified in grams, and the values should add up to a total of 1 gram. The energy parameter should be specified in mmol, and there is no limit on the value of this parameter. If you want to create an empty biomass reaction and populate the reaction compounds manually yourself, simply set all the component values to zero. Note, you cannot create a biomass equation and edit the stoichiometry of that new biomass equation at the same time. You have to run the App once to make the biomass equation, then run it again to edit the equation.
Changing biomass stoichiometry in the model
Now, regarding the change biomass stoichiometry feature, this capability allows you to alter or even remove a compound from an existing biomass reaction. Note, you cannot change a biomass reaction that does not exist yet, and you cannot add a compound to a biomass if the compound is not in the model. To add a new compound to a biomass reaction, you must first add the compound to the model using this App, then run the App again to change the stoichiometry of the compound in the specified biomass. The stoichiomety can be negative (for compounds consumed during growth) or positive (for compounds produced during growth). If you set the stoichiometry to zero, it will remove the compound from the biomass reaction.
Adding new compounds to the model
You can use this App to add any new compound to the model. It does not need to be a ModelSEED compound. However, it is recommended to first check if a compound is present in the ModelSEED (by searching for the compounds on modelseed.org). If the compound is in the ModelSEED, then use the cpd##### ID for the compound when adding it to the model. This spares you from needing to specify a formula, charge, or name of the compound, as this information will be pulled from the ModelSEED. If your compound is not in the ModelSEED, you can specify your own ID, but note that the ID cannot contain spaces and must be unique. When specifying your own compound, be sure to specify an accurate human readable name, formula, and charge for the compound. The formula and charge in particular will be used by tools in KBase to check the mass and charge balance of reactions in your model. Note, you must add a compound to your model before you can use the compound in any reaction or biomass function in the model.
Changing compounds in the model
If you decide you want to change a compound s name, or think the charge or formula of a compound is incorrect, you can use these controls to alter these attributes of the compound in the model.
Adding reactions to a model
This App also permits you to add new reactions to your metabolic model. Here, you specify the reaction ID. Note that this ID must be unique within each compartment in the model (the same reaction *can* occur in multiple compartments), and it cannot contain spaces. Generally try and avoid _ in IDs, as the _ is used internally as a delimiter between reaction IDs and compartment IDs. The new reaction being added does not need to be a ModelSEED reaction, but if a reaction is in the ModelSEED (which you can determine by searching in the modelseed.org for the reaction), we strongly recommend using the ModelSEED ID for the reaction as the reaction ID. If you do specify a ModelSEED reaction ID, all data about the reaction, including stoichiometry, will be ported from the ModelSEED database. It will not be necessary to separately specify the stoichiometry of the reaction. If you don t specify a ModelSEED reaction, you will need to add your new reaction first, then run this App a second time to specify the stoichiometry of the compounds in the reaction. This is because you cannot specify the stoichiometry of a reaction that is not yet in the model in this App. In addition to the ID, you can also specify the directionality, human readable name, compartment, and GPR (gene-protein-reaction) association of the reaction. Directionality indicates the direction in which the reaction is able to proceed when simulating flux balance analysis (FBA) with the model. => means forward only; <= means reverse only; and <=> means reversible. The compartment indicates the cellular location where the reaction takes place. For non-transport reactions, all compounds in the reaction should also occur in the same primary compartment as the reaction. For transport reactions, always choose the inner-most compartment as the compartment for the reaction. Finally, the GPR indicates how the reaction activity depends on gene activity in the cell. This is represented as a string containing gene IDs and boolean condition statements (e.g. "(b0001 or b0002) and b0003").
Adding and adjusting compound stoichiometry in a reaction
Finally, we will discuss the ability to adjust the stoichiometry of a particular compound in the reactions in your model. In this portion of the App, you can select from a pre-existing reaction and compound in the model, then specify the stoichiometric coefficient of the selected compound in the selected reaction. A negative coefficient means the compound is a reactant in the reaction, while a positive coefficient means the compound is a product. The coefficient can be set to 0 to remove the compound from the reaction.
- Arkin AP, Cottingham RW, Henry CS, Harris NL, Stevens RL, Maslov S, et al. KBase: The United States Department of Energy Systems Biology Knowledgebase. Nature Biotechnology. 2018;36: 566. doi: 10.1038/nbt.4163 , https://www.nature.com/articles/nbt.4163
- Henry CS, DeJongh M, Best AA, Frybarger PM, Linsay B, Stevens RL. High-throughput generation, optimization and analysis of genome-scale metabolic models. Nat Biotechnol. 2010;28: 977 982. doi:10.1038/nbt.1672 , https://www.ncbi.nlm.nih.gov/pubmed/20802497
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