Molecular_Interaction_Maps

TableOfContents([2])

About this document

This is an official Request for Comment (RFC) for Supporting Molecular Interaction Maps in Cytoscape.

For details on RFCs in general, check out the [http://www.answers.com/main/ntquery?method=4&dsid=2222&dekey=Request+for+Comments&gwp=8&curtab=2222_1&linktext=Request%20for%20Comments Wikipedia Entry: Request for Comments (RFCs)]

Status

* preliminary draft, still brain-dead, take with a grain of NaCl.

How to Comment

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Proposal

A Molecular Interaction Map (MIM) is a diagram convention that is capable of unambiguous representation of networks containing multi-protein complexes, protein modifications, and enzymes that are substrates of other enzymes. MIMs are described in detail at http://discover.nci.nih.gov/mim/index.jsp and in a seminal article by Kohn et al at http://www.molbiolcell.org/cgi/content/abstract/E05-09-0824v1

An example MIM is below attachment:mim_eg.png

MIMs have been developed at the National Cancer Institute (specifically the Laboratory of Molecular Pharmacology). They are looking into what it would take to develop an Editor to create Molecular Interaction Maps (MIMs) in an editor to yield both a graphical view and a computer-readable format (preferrably BioPax). They are interested in seeing if such a MIM editor could be developed for Cytoscape.

MIM symbols are defined in the figure below:

attachment:Kohn_SymbDefH3.jpg

QUESTION: Is this the most recent definition of map symbols? In particular, are site-specific constructs, such as cleavage, still defined as requirements?

This proposal will specify the mapping between MIM constructs and their proposed counterparts in Cytoscape. A prioritized set of requirements will be presented. Enhancements needed in the editor, renderer, and/or other Cytoscape components will be identified.

Biological Questions / Use Cases

• Cleavage

• CompoundBinding

• CovalentBinding

• Inhibition

• SimpleBinding

General Notes

From an initial reading of the article by Kohn et al at http://www.molbiolcell.org/cgi/content/abstract/E05-09-0824v1, an initial description of potential mappings between MIM and Cytoscape constructs was derived. This is summarized in the figure below.

attachment:kohn_mappings.png

Further Notes from meeting at 2006 Cytoscape Developers Retreat

• Need to map MIM to both model and view
  • How to represent 'non covalent binding'?
    • Model: Best mapped to a group. A and B are connected and are part of the group.
    • View: this is a use case for the group view
  • Asymmetric binding
    • Model: Regular edge between A and B, just needs a specific edge type
    • View: New type of custom edge graphic (will take some care with Nerius' edge drawing code)
  • Representation of multimolecular complexes
    • Model: A group of groups
    • View: part of the use case for group view
  • Covalent modification of protein A (post-translational modification = PTM)
    • Model: A is a node (representing unmodified protein); central node is a node (represented modified A) - every state is represented as a node. The PTM e.g. P is not a node, it is an annotation on the 'central' state node. The edge between A and its state is of type 'state of'. The set of all states is grouped to represent the set of all states of A.
    • View: Constraint: the states always move together (would be like a template)
  • Cleavage of of a covalent modification of protein A
    • Model: Hyperedge containing node1: Phtase (hyperedge attribute: enzyme), node2: phosphorylated A, node3: unphosphorylated A
    • View: Use case for hyperedge view
• General constraints for automatic layout and the editor
  • Snap to grid
  • All lines need to be routed with only right or acute angles
  • Central node is only there if it is used (connected to something else in the diagram)
• Next step: a special interest group should get together to hash the above out further. Current interested people are: Allan, Mirit, David, Gary, Aditya, Scooter, Alex; also general interest from Nathan, Kristina (GenMAPP editing), Ethan, Ben (BioPAX editing)
• Implementation: Cytoscape core would ensure that the model and view requirements are met. Users: like GenMAPP, MIM, BioPAX editing would use the core functionality to create their own plugins that implemented their own pathway editing features.

Requirements

Deferred Items

Open Issues

1. Do they need site-specific connection of edges, e.g. as in proteolytic cleavage? From Mirit's presentation, it appears that metanodes would work just fine.
2. How do we represent the "null" node, as in degradation product?
3. How do we represent "ditto" nodes, e.g. as in translocation?
4. Would they need editor support for Manhattan topology, e.g. constraints on edge angles?

Backward Compatibility

Expected growth and plan for growth

References

Implementation Plan

• [:Molecular Interaction Maps/Implementation Plan:/Implementation Plan]

Comments

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