Proposal: Model "activation" as MIM stimulation

[Eric Weitz]

Hi WikiPathways,

Many interactions use a generic arrow glyph to represent "activation", i.e. upregulation or increasing expression.  Modeling these as a MIM "stimulation" seems semantically richer and more useful.

Would it make sense to recommend that in editing guidelines?

Definitions

Stimulation is defined as "Enhancement of the velocity or extent of a reaction or contingency by the controller entity" in the Formal MIM Notation Specification.  

Arrow is described in Help:Guidelines_EditorPalette: "The solid line and arrow are used to denote a variety of processes when the more specific mim-interactions are not appropriate, including translocation and activation."

Examples and relations

The examples in the linked Editor Palette Guideline show "stimulation" as an interaction between a metabolite and gene.  Many pathways, e.g. WP622, use legends to define generic arrow as "activates / upregulates", and use it between one gene and another gene (whether as a group or not).   

Upregulation or increasing gene expression seems to satisfy the definition of stimulation: gene expression (DNA transcription) is a reaction, and upregulating or activating it seems like "Enhancement of the velocity or extent of a reaction or contingency by the controller entity".

Proposal

So activation seems equivalent with stimulation.  However, the linked Editor Palette guidelines imply they differ -- "The solid line and arrow are used to denote a variety of processes when the more specific mim-interactions are not appropriate, including translocation and activation".

Given the definitions and examples above, would it be reasonable to update that guideline to recommend modeling activation interactions with the as MIM stimulation interaction types?

If not, what are some examples of activation that are not stimulation, per the MIM definition above?

Thanks,

Eric

[Kristina Hanspers]

Hi Eric,

We definitely need to update/overhaul the guidelines and at this point an update will probably coincide with the release of the new GPML schema, which adds support for additional interaction types. 

For the specific question of how stimulation is described in our current guidelines, the example (interaction between metabolite and gene), is not great because it doesn't capture how it is most often used. The most common use of it, and the way I interpret the MIM example maps, is similar to mim-catalysis, to indicate that an entity has an effect on a reaction, rather than on another entity. However, it is also used between entities, in the MIM maps and at WikiPathways. Here's an example that includes both:

https://www.wikipathways.org/index.php/Pathway:WP4962

Do you have examples of specific pathways where you think mim-stimulation should be used? 

It would be great to hear from the rest of the team on this as well. I don't recall all our previous discussions about when to recommend a specific mim interaction type. 

Regards,

Kristina

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[Eric Weitz]

Hi Kristina,

Thanks for linking me to those MIM example maps.  

> Do you have examples of specific pathways where you think mim-stimulation should be used?

Yup!  Pathways where an arrow noted as "Activation" in a legend could be upgraded to mim-stimulation for matching interactions:

• WP622
• WP1530
• WP4857
• WP4874
• WP4884

There are likely a few dozen more.  

An arrow merely entails "A acts on B", whereas the MIM type lets one infer "A stimulates B" -- much more useful.  Upgrading the end marker type from generic arrow to mim-stimulation in such cases would enrich downstream applications that build on WikiPathways.

Cordially,

Eric