Resolutions

Nomenclature

• The description State Transition diagram can be misleading and may not be strictly correct.
• The ST diagrams are now called Process diagrams.
• Correspondingly State Node and State Transition Node have been renamed (respectively):
  • Entity Pool Node
  • Process Node

Source/Sink

• Source and Sink should be regarded as syntactically different, but have the same Glyph.
• These nodes should only be assigned to 1 arc (degree 1).

Multimer

• For consistency it was agreed that there should also be a consistency arc.

Perturbation

This is a new Glyph that provides the ability to describe an external influence on a process. It will be an anvil shaped symbol and can only be associated with a modulating arc.

Phenotype

A phenotype is phenomenon external to the system that can be caused by a process in an SBGN diagram. An example would be apoptosis. The glyph will be a hexagon and will only be the target of a modulation arc.

Complexes

Complexes will remain as they are however it was clarified that:

1. Their subunits are shown explicitly (although this should not be used to imply topology).
2. Complexes and be nested.
3. Complexes can span compartments.
4. Subunits can be shown to modulate a process.

Modules/Submap

• The semantics of a module was simplified to be a Submap. Module semantics and interface definition was found to be complex and so deferred to a later version.
• A module is now called a Submap, which has the same glyph.
• The Entity Pools Nodes that map to those in the main diagram are indicated by a tag.
• The Submap glyph contains one or more squares containing the tag id of each Entity Pool Node in the Submap.
• Entity Pool Nodes in the main diagram are linked to only one square in the Submap glyph by an equivalence arc to indicate a mapping between main map and sub-map.

Tags

• Tags are now only used to indicate nodes in a submap that map to the main map.
• Tags are not now used for cloning - see below.

Equivalence Arc

• This type of arc is missing in the existing specification but require: which was a bug.
• The equivalence arc is used to link an Entity Pool Node to a Tag or submap and indicates that the Pool Node “maps to” or is “equivalent to” to the other end of the link.

Logic Arc

• This arc was also missing from the spec and is also implies, but not specified it (another bug).
• The Logic arc is require as an “input” arc to a Logic gate.

Delay

• This has been deferred to a later version of SBGN.

Stoichiometry

• A label can be associated with Consumption or Production arc indicating the stoichiometry of a process.
• This is required to eliminate ambiguity when the exact composition of the number of copies of the inputs or outputs to a reaction are ambiguous from the diagram. An example is a multimer of 6 subunits dissociating into 2 monomers and 2 dimers. Without stoichiometry labels another result, such as 4 monomers and 1 dimer could be inferred.

Cloning Entity Pool Nodes

By cloning we mean displaying 2 or more identical Entity Pool Nodes in the same map (See spec semantics section for a detail description of identity in process diagrams).

• Cloned Entity Pool Nodes should be marked as such.
• Clones will be marked using a identified label in a Stateful Entity Pool Node.
• Clones will be marked as a filled bottom in a Non-Stateful Entity Pool Node.

See solution shown below:

http://assets.drop.io_download_47a14a92_296f274ae76c1da5ec620de613d6b43d6e891831_04ffcc60-b1e0-012a-aa8d-00127994f632_81a148d0-b1e0-012a-8985-fc3c183d16d0_dsc_0553.jpg

Translocation of Compartments

It was discussed whether and how SBGN can describes cellular process that involve the movement of vesicles or other compartments about the cell and which it would be useful to describe the different stages in this process. Examples are endocytosis or synaptic vesicle trafficking.

• SBGN Level 1 will not try and address this issue with new mechanisms.
• Vacuoles in their different stages can be shown as different compartments.
• No arc will be used to show progress from one to the other. The user must rely on unstructured annotation of the diagram.

Process Node Compartments

Process nodes can be used to describe process that start in one compartment and end up in another. In such cases is the container the transition is located in significant?

• Since a Process Node can describe multiple biochemical processes they cannot belong to a compartment.
• To ensure aesthetic layout the Process Node should be in the same compartment as at least one of its participants or in the “empty” compartment.

Additional graphical attributes within SBGN diagrams

It would be very helpful if additional information connected to nodes and arcs/edges could be shown within a drawing. Such information could be, for example, experimental or simulation data.

Additional information connected to network elements (nodes and edges) could be expressed by colour, size (width), diagrams and other graphical attributes. Therefore in the specification of SBGN

1. colour should not be used (no assumption about the clour of a glyph)
2. the size of nodes and the width of edges should not carry any meaning within SBGN (no assumption that, for example, a transition node is smaller than a node for a single molecule).
3. labels(text) should be freely placed within the glyph (The problem in the current spec is, that often label boxes have to be attached to the center of the container box.)

All issues were agreed as above with variations to the last issue. Text layout should follow the following rules:

• At least a part of the label (unbordered box containing a string of characters) has to be with the node it belongs to. Node labels are not allowed to overlap nodes or other labels (this includes touching of other nodes or labels).

1. Edge labels are not allowed to overlap nodes (this include touching of nodes).
2. Compartments: if all participants of a transition are in the same compartment the transition node and all edges/arcs have to be in this compartment.

1. Labels should be horizontal. Node labels should be placed completely inside the node if possible. Edge labels should be placed close to the edge and avoid overlapping the edge as well as other edge labels.

Edge Layout

There should be two extra rules in the layout part of spec:

• Edge should not cross itself.
• Edge should cross compartment boundary only once.

Gene Regulation

1. A new Glyph will be created called Genomic Entity which is a “Fragment of a macromolecule that carries genomic information”.
2. Gene regulation is therefore described by binding to Genomic Entities that describe regulatory regions of the gene - binding being described as a complex.
3. The Genomic Entity is stateful and can have state variables and units of information.

See example from HK below (note that the glyphs are different):

http://assets.drop.io_download_47a26e2b_d83051979735c49bb7e5992a5187d81add923aed_04ffcc60-b1e0-012a-aa8d-00127994f632_29ae76d0-b28e-012a-27dc-f27f77bb0d47_ipscell_large.jpg

The following issues need to be addressed for Level 1 but are not completely “solved”.

Compartments

• Compartments can be drawn as containing other compartments (also called nesting).
• Nesting does not imply a hierarchy of compartments, e.g. “the nucleus is inside the cytoplasm”.
• Compartments can have any shape and need not be rectangular.

Compartment Spanning

This issue was “resolved” in the last plenary session, but problems were raised with it during discussion on the last day of the Hackathon. Given that this is a very significant change to SBGN semantics this does need further work. See the discussion and issues page for more detail of the issues.

This is a tricky problem with no clear solution given that:

1. The biologist expects to see TM proteins spanning a membrane (i.e. drawn over 3 compartments)
2. The safest and simplest semantics would only permit a complex or macromolecule to belong to one compartment (this is what BioPAX level 3 does).