Inferred pathways

Manually inferred pathways

Manual inference of human events from model organism data

Reactome aims to represent human pathways, but sometimes experimental data is only available from a model organism. Under these circumstances the data from the model organism is used to manually infer the human event.

First a reaction is created that defines the molecular event in the model organism. This data is then used to infer an equivalent human reaction (Figure 8). These are only included if both the expert author and the reviewer agree that a human event can be directly inferred from the experimental data. Inferred events will have no direct literature references; they will instead cite the relevant model organism literature. Both the inferred human and model organism reactions are available to view in the database.

Computationally inferred pathways

Computational inference of non-human events from human data

While the focus of Reactome is human pathways the database also contains equivalent pathways for divergent model organisms. These pathways are computationally inferred using the manually curated human pathways as a template. The represented species include: Rattus norvegicus, Danio rerio, Caenorhadbitis elegans, and Arabidopsis thaliana. The inference process is based on orthology predictions obtained from Ensembl Compara.

In the above example (Figure 9) the human reaction has two proteins – A and B. Both have orthologues in mouse but not in fly. This evidence would mean that the event would not be inferred in fly, and the fly pathway would not represent it as a reaction. On the other hand, it is likely that this event occurs in mouse.