Re: [Gusdev-gusdev] GUS 3.0 schema changes

[Joan M. <ma...@pc...>]

Hi,

(I think in this use case there are two things we want to represent.
* First is that an effector, E3, let's say activates the formation of
Complex C1, made of two proteins, P1 and P2.
* Second is how E3 activates the formation of C1. For example E3 is a
kinase and by phosphorylating P1, it induces the dimerization of P1 and
P2 to form C1.)

So just for me:

entity 3 (E3) interacts with P1 (unphosphorlated); (phosphorlated) P1 can now interact with
P2

So P1 has two states, one is phosphorylated in which it acts as a
complex component, the other one is unphosphorylated. Would it be worth
to represent these two states of a protein (or more generally
active/inactive states) ?


Yes, but I think this gets into something that interaction does not strictly cover.  And
the answer requires thinking about GUS proteins.

So the protein involved in the interaction is not the same, in other words, in protein
land, it has a phosphorlated residue which participates in the interaction, so I think in
the database we would have to say this is a new "instance" of the protein (I am not sure
this is the right word to use) ....so there was a RNA which has a protein associated with
it and then this protein is modified which changes not strictly its overall amino acid
sequence but one of its amino acids "chemical nature".  (although protein instances
(sequences) derived for an RNA can vary depending on the "source".)  If we can represent
both the proteins forms (phosphorlated and unphos.) somehow, we could use the form which
does the interacting as the entity (effector) in the interaction table.
But I think this gets into protein areas which we have not discussed in any depth because
we would have to be able to create the feature on the amino sequence (ie amino acid 23 of
this amino acid sequence is phosphorlated).  I guess something like the amino acid residue
S at position 200 has been changed to S*.
This gets into how to handle postranslational protein modifications.  I think you may have
had some discussions with Crabtree on this.
Do you currently have away to do this when annotating or do you just have this info.
associated in the protein (e.g., protein X is phosphorlated on residue 34; pubmed
reference)?


Joan

Arnaud Kerhornou wrote:

> Hi
>
> Joan Mazzarelli wrote:
>
> >Hi Jonathan,
> >
> >*formation* (e.g. dimerization)?  Assuming that we had reason to explicitly
> >represent the formation of a Complex (versus the mere fact of its existence,
> >which is handled by Complex/ComplexComponent), wouldn't this be done with
> >the Interaction table?  If it were, then you'd have to be able to support
> >multiple effectors.  To represent dimerization, for example, you'd have
> >2 inputs (effectors) and 1 output (the target.)  The effectors would be
> >the same entities referenced by the ComplexComponents and the target would
> >be the Complex itself.  This sounds redundant, but if (yet another
> >hypotheticals) you wanted to represent the fact that a second or third
> >protein acted to inhibit the dimerization process (through some as-yet-
> >undetermined mechanism) then you'd need to create the dimerization
> >Interaction so that you could reference it in yet another Interaction (as
> >a target being inhibited by the new protein).
> >
> >
> I think It makes sense representing the dimerization by an interaction.
> This way we can differenciate that an effector modulates the activity of
> Complex C1 from another situation where another effector modulates the
> formation of C1, even though one could argue that regulating the
> formation of C1 is likely to also regulate the activity of C1!
>
> I think in this use case there are two things we want to represent.
> * First is that an effector, E3, let's say activates the formation of
> Complex C1, made of two proteins, P1 and P2.
> * Second is how E3 activates the formation of C1. For example E3 is a
> kinase and by phosphorylating P1, it induces the dimerization of P1 and
> P2 to form C1.
>
> So P1 has two states, one is phosphorylated in which it acts as a
> complex component, the other one is unphosphorylated. Would it be worth
> to represent these two states of a protein (or more generally
> active/inactive states) ?
>
> >Yes this is true.  Think modeling all interactions regardless of knowing that they
> >form a dimer complex.
> >
> >If we take out the effect-target wording in the interaction table and say:
> >entity 1 (effector) interacts withe entity 2 (target) to create a dimer; entity 1can
> >equal entity 2
> >
> >Entity 1 interacts with entity 2 ; now if a third entity inhibits the dimerization
> >between 1 and 2 than entity 3 would need to be able to interact with entity 1 (or 2).
> >
> >I think the trouble comes in when if you had a dimer or a 2 component complex (entity
> >1 and entity as a complex) and the entity 3 could only interact with the complex to
> >disassemble it (or on the molecular level you need surfaces of both entity 1 and
> >entity 2 for interaction with entity 3).
> >
> >I think maybe saying that the complex of 1 and 2 interacts with entity 3 takes care of
> >this, but this uses both the interaction table and the complex table to assign the
> >complex of 1 and 2 as interacting with entity 3.
> >
> >I think that the terms effector and target are confusing in the interaction table.
> >Actually when we originally designed the interaction table I am remembering we
> >struggled with these words, but if we now have direction is known (or not known) in
> >the table do we need effector-target?  I am not sure about this.
> >Also the line of evidence tables for interaction may assume that you are only adding
> >evidence for a single direct interaction even if there are multiple lines of evidence
> >to support the interaction (yeast 2 hybrid exp., invitro binding exp.).
> >
> >Joan
> >
> >
> >
> Arnaud

--
Joan Mazzarelli
Computational Biology and Informatics Laboratory
Center for Bioinformatics
1429 Blockley Hall
University of Pennsylvania
Philadelphia, PA 19104