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Propagate Model to New Genome


By: chenry


Translate the metabolic model of one organism to another, using a mapping of similar proteins between their genomes.

Accurate metabolic models are based on well-curated genome annotations which are labor intensive and thus highly valuable. This App permits users to construct a metabolic model of a new organism based on either a previously published or user-curated model in another organism, rather than constructing and curating it ab initio.

The quality of the propagated model will depend on how closely related the target and source genomes are because gene-to-gene function connections between the two are inferred from sequence homology. Therefore the App has two required inputs: (i) a source model to be propagated and (ii) a proteome comparison map between the source and the target organism.

(i) The input source model can be either one previously created externally and then imported into KBase or one generated within the system with the Build Metabolic Model App. (See here for instructions on import a genome into KBase).

If creating a new model in KBase using this App, we recommend first performing a literature search for available published model(s) for organisms closely related to the target organism. To aid in this process the Insert Genome Into Species Tree App can be used to find closely related organisms to look for when searching the literature.

Since the purpose of this App is to take advantage of the additional information provided by a curated model that our automated generated models may be missing, we do not recommend using a model generated via the Build Metabolic Model App as a source, unless curation is introduced. Curation can be performed in KBase using the Edit Metabolic Model App.

(ii) Generating the necessary protein comparison requires the use of the Compare Two Proteomes App to identify genes encoding potentially orthologous proteins in the two organisms. Best results are obtained when the source and target genomes are closely related, as higher-confidence functional inferences may be drawn from the higher homology of protein pairs between the two organisms. Additionally, the transferred model may suggest missing annotations in the target genome, thus improving the quality of its annotation.

The method applies the following rules in order to decide whether to propagate a reaction or not:

  1. If the reaction associates with one or more genes in the original (source) model, but none of those genes has an ortholog in the new genome, the reaction is deleted.
  2. If the reaction associates with no genes in the original model, then the action taken depends on whether or not the "Keep reactions with no genes" option is checked (the reaction is retained if checked, otherwise it is removed). By checking the box, the user is making the assumption that both species have the same gaps in the enzymatic annotation of their genomes.
  3. If the reaction has one or more genes in the original model and at least one has a homolog in the new genome, then the reaction is retained, and all genes with homologs are translated and retained.

App Output
There are eight separate tabs for browsing the data in the model:

For additional information about metabolic modeling, visit the Metabolic Modeling in KBase FAQ.

Team members who developed & deployed algorithm in KBase: Chris Henry, Janaka Edirisinghe, Sam Seaver, and Neal Conrad. For questions, please contact us.

Related Publications

App Specification:

Module Commit: 8c19fee066af8267b5eadf85f5b4fb2f6eef8027