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[cellml-discussion] Using proposed CellML 1.2 features to create more re-usable metabolic models


Chronological Thread 
  • From: m.cooling at auckland.ac.nz (Michael Cooling)
  • Subject: [cellml-discussion] Using proposed CellML 1.2 features to create more re-usable metabolic models
  • Date: Thu, 31 Jan 2008 10:17:01 +1300
First just to check that in the the connection elements 'flux' should
be 'fluxes'? For example, 'substance_a' component contains no variable
'flux', I assume you meant the set_of_lambda_of_real 'fluxes'?

I think I like this! When will it be released? ;-P

I don't know enough about the lambda elements in MathML to check the
syntax (BTW which MathML spec would we use for CellML 1.2, MathML
2.0?) but I think I get the idea and presuming it works like how the
species are tracking their own ODEs and the reactions just deal in
fluxes for the species involved. We can do this with cellml 1.0 but
better to minimise the 'gluing code' of course.

Minor question: what is the purpose of the component abxy_system? Is
this to help monitor the individual fluxes from one location?

Very minor point: I notice the units for your kb terms should be just
'per_second'?

directionality - I suspect we can just leave those redundant (in/out)
tags out?

connections structure - makes me think about something that is more a
toolset UI issue:
One thing I've found when constructing models is that I don't think
about connections
from an A->B, then A->C then A->D perspective (letters here are
components), but by considering all connections from A to other
components. For example, if I have a new component A I'd much rather
declare something like:

<connections from A>
<variable whatever1 to B:whateverinB>
<variable whatever2 to C:whateverinC>
</connections from A>

if you see what I mean, rather than hunt around the CellML for each
variable connection which is, in my opinion, tedious and poor
workflow. Now I don't think what I've written there is as good a
structure as the current CellML and I'm not suggesting CellML should
be changed, but what I'm getting to is I think it would be helpful for
the PCEnv/COR tool if from the UI a more workflow-friendly linking was
possible, and it sorted out the more elegant connection components as
written in CellML from that.

Cheers,


Quoting Andrew Miller <ak.miller at auckland.ac.nz>:

> Hi all,
>
> To aid in working out what features we should include in CellML 1.2, I
> have been looking into one of the major difficulties with creating
> re-usable metabolic models at the moment: that to compute a derivative,
> you need to know all the fluxes, but when a model is extended, new
> fluxes can be added to the model. Ideally, we should be able to define
> CellML 1.2 so that structured types can be leveraged to avoid this issue.
>
> I have come up with an example of how this might look in CellML 1.2.
> This is based in part off a discussion that I had earlier with Poul, so
> most of the credit for this goes to him, while most of the blame for the
> inelegant parts goes to me.
>
> Note that the lambda constructs without any bound variables are there to
> defer interpretation of the fluxes until they are taken from the set.
> The rationale for needing this is that if we had two statements that a
> certain real-valued flux belongs in the set, and two of them happened to
> have the same value at a particular point in time, then summing over the
> set would only include the flux value once (e.g. saying x is an element
> of N, where N is in the natural numbers, means that the value of x is a
> natural number. Saying x=5, y=5, x in N, y in N does not mean that 5 is
> in the set of natural numbers twice). On the other hand, we can have two
> different zero argument lambda functions in a set, which just happen to
> evaluate to the same value. This is consistent with the declarative
> nature of CellML - we are not saying 'add this flux to the set of
> fluxes', but rather, we are making a series of statements about what is
> in the set of fluxes, and the processing software is then summing over
> all fluxes which have been explicitly mentioned. Because we can connect
> the set of fluxes up to an importing model, doing things this way gives
> a great deal of extra flexibility.
>
> Notes:
> 1) In practice, the substance could become an import which is re-used
> many times, and likewise for components representing various general
> types of chemical reactions.
> 2) I have invented a possible way in which we could remove
> directionality from connections. No one has come up with a formal
> proposal to do it this way yet.
> 3) I have followed Randall's earlier suggestion about how to structure
> connections without using component_ref. This again needs a formal
> proposal and discussion.
> 4) The model uses a potential way in which we could get rid of the
> generality of groups, by replacing group and relationship_ref with a
> simple encapsulation element. This again needs to be formally proposed
> and discussed at some point.
>
> <?xml version="1.0" encoding="UTF-8"?>
> <model
> xmlns="http://www.cellml.org/cellml/1.1#";
> xmlns:c11="http://www.cellml.org/cellml/1.1#";
> xmlns:c12="http://www.cellml.org/cellml/1.2#";
> xmlns:m="http://www.w3.org/1998/Math/MathML";
> name="_1_2_example"
> >
> <component name="substance_x">
> <c12:variable name="fluxes" type="set_of_lambda_of_real"
> units="mol_per_litre_per_second" public_interface="yes" />
> <c12:variable name="concentration" units="mol_per_litre"
> public_interface="yes" />
> <c12:variable name="time" units="second" public_interface="yes" />
> <m:math>
> <m:apply><m:eq/>
> <m:apply><m:diff/>
> <m:bvar><m:ci>time</m:ci></m:bvar>
> <m:ci>concentration</m:ci>
> </m:apply>
> <m:apply><m:sum />
> <m:bvar><m:ci>f</m:ci></m:bvar>
> <m:condition>
> <m:apply>
> <m:in/>
> <m:ci>f</m:ci>
> <m:ci>fluxes</m:ci>
> </m:apply>
> </m:condition>
> <m:apply>
> <m:ci>f</m:ci>
> </m:apply>
> </m:apply>
> </m:apply>
> </m:math>
> </component>
>
> <component name="substance_a">
> <!-- Identical to substance_x. This would normally be defined once
> and imported.
> -->
> </component>
>
> <component name="substance_b">
> <!-- Identical to substance_x. This would normally be defined once
> and imported.
> -->
> </component>
>
> <component name="substance_y">
> <!-- Identical to substance_x. This would normally be defined once
> and imported.
> -->
> </component>
>
> <!-- Represents a reaction A + B -> X -->
> <component name="reaction_a_b_x">
> <c12:variable name="concentration_a" units="mol_per_litre"
> public_interface="yes" />
> <c12:variable name="concentration_b" units="mol_per_litre"
> public_interface="yes" />
> <c12:variable name="concentration_x" units="mol_per_litre"
> public_interface="yes" />
> <c12:variable name="flux_a"
> public_interface="yes"
> type="set_of_lambda_of_real"
> units="mol_per_litre_per_second" />
> <c12:variable name="flux_b"
> public_interface="yes"
> type="set_of_lambda_of_real"
> units="mol_per_litre_per_second" />
> <c12:variable name="flux_x"
> public_interface="yes"
> type="set_of_lambda_of_real"
> units="mol_per_litre_per_second" />
> <variable name="kf" units="litres_per_mol_per_second"
> initial_value="0.5" />
> <variable name="kb" units="litres_per_mol_per_second"
> initial_value="0.1" />
> <variable name="overall_rate" units="mol_per_litre_per_second" />
> <m:math>
> <m:apply><m:eq/>
> <m:ci>overall_rate</m:ci>
> <!-- First order law of mass action... -->
> <m:apply><m:minus/>
> <m:apply><m:times/>
> <m:ci>kf</m:ci>
> <m:ci>concentration_a</m:ci>
> <m:ci>concentration_b</m:ci>
> </m:apply>
> <m:apply><m:times/>
> <m:ci>kb</m:ci>
> <m:ci>concentration_x</m:ci>
> </m:apply>
> </m:apply>
> </m:apply>
> <m:apply><m:in/>
> <m:lambda>
> <m:apply><m:minus/>
> <m:ci>overall_rate</m:ci>
> </m:apply>
> </m:lambda>
> <m:ci>flux_a</m:ci>
> </m:apply>
> <m:apply><m:in/>
> <m:lambda>
> <m:apply><m:minus/>
> <m:ci>overall_rate</m:ci>
> </m:apply>
> </m:lambda>
> <m:ci>flux_b</m:ci>
> </m:apply>
> <m:apply><m:in/>
> <m:lambda>
> <m:ci>overall_rate</m:ci>
> </m:lambda>
> <m:ci>flux_x</m:ci>
> </m:apply>
> </m:math>
> </component>
>
> <!-- Represents a reaction A + X -> Y -->
> <component name="reaction_a_x_y">
> <c12:variable name="concentration_a" units="mol_per_litre"
> public_interface="yes" />
> <c12:variable name="concentration_y" units="mol_per_litre"
> public_interface="yes" />
> <c12:variable name="concentration_x" units="mol_per_litre"
> public_interface="yes" />
> <c12:variable name="flux_a"
> public_interface="yes"
> type="set_of_lambda_of_real"
> units="mol_per_litre_per_second" />
> <c12:variable name="flux_y"
> public_interface="yes"
> type="set_of_lambda_of_real"
> units="mol_per_litre_per_second" />
> <c12:variable name="flux_x"
> public_interface="yes"
> type="set_of_lambda_of_real"
> units="mol_per_litre_per_second" />
> <variable name="kf" units="litres_per_mol_per_second"
> initial_value="0.5" />
> <variable name="kb" units="litres_per_mol_per_second"
> initial_value="0.1" />
> <variable name="overall_rate" units="mol_per_litre_per_second" />
> <m:math>
> <m:apply><m:eq/>
> <m:ci>overall_rate</m:ci>
> <!-- First order law of mass action... -->
> <m:apply><m:minus/>
> <m:apply><m:times/>
> <m:ci>kf</m:ci>
> <m:ci>concentration_a</m:ci>
> <m:ci>concentration_x</m:ci>
> </m:apply>
> <m:apply><m:times/>
> <m:ci>kb</m:ci>
> <m:ci>concentration_y</m:ci>
> </m:apply>
> </m:apply>
> </m:apply>
> <m:apply><m:in/>
> <m:lambda>
> <m:apply><m:minus/>
> <m:ci>overall_rate</m:ci>
> </m:apply>
> </m:lambda>
> <m:ci>flux_a</m:ci>
> </m:apply>
> <m:apply><m:in/>
> <m:lambda>
> <m:apply><m:minus/>
> <m:ci>overall_rate</m:ci>
> </m:apply>
> </m:lambda>
> <m:ci>flux_x</m:ci>
> </m:apply>
> <m:apply><m:in/>
> <m:lambda>
> <m:ci>overall_rate</m:ci>
> </m:lambda>
> <m:ci>flux_y</m:ci>
> </m:apply>
> </m:math>
> </component>
>
> <component name="abxy_system">
> <c12:variable name="concentration_a" units="mol_per_litre"
> public_interface="yes" />
> <c12:variable name="concentration_b" units="mol_per_litre"
> public_interface="yes" />
> <c12:variable name="concentration_x" units="mol_per_litre"
> public_interface="yes" />
> <c12:variable name="concentration_y" units="mol_per_litre"
> public_interface="yes" />
> <c12:variable name="flux_a"
> public_interface="yes"
> type="set_of_lambda_of_real"
> units="mol_per_litre_per_second" />
> <c12:variable name="flux_b"
> public_interface="yes"
> type="set_of_lambda_of_real"
> units="mol_per_litre_per_second" />
> <c12:variable name="flux_x"
> public_interface="yes"
> type="set_of_lambda_of_real"
> units="mol_per_litre_per_second" />
> <c12:variable name="flux_y"
> public_interface="yes"
> type="set_of_lambda_of_real"
> units="mol_per_litre_per_second" />
> </component>
>
> <c12:connection component_1="substance_a" component_2="reaction_a_b_x">
> <variable_ref variable_1="concentration" variable_2="concentration_a" />
> <variable_ref variable_1="flux" variable_2="flux_a" />
> </c12:connection>
> <c12:connection component_1="substance_b" component_2="reaction_a_b_x">
> <variable_ref variable_1="concentration" variable_2="concentration_b" />
> <variable_ref variable_1="flux" variable_2="flux_b" />
> </c12:connection>
> <c12:connection component_1="substance_x" component_2="reaction_a_b_x">
> <variable_ref variable_1="concentration" variable_2="concentration_x" />
> <variable_ref variable_1="flux" variable_2="flux_x" />
> </c12:connection>
>
> <c12:connection component_1="substance_a" component_2="reaction_a_x_y">
> <variable_ref variable_1="concentration" variable_2="concentration_a" />
> <variable_ref variable_1="flux" variable_2="flux_a" />
> </c12:connection>
> <c12:connection component_1="substance_x" component_2="reaction_a_x_y">
> <variable_ref variable_1="concentration" variable_2="concentration_x" />
> <variable_ref variable_1="flux" variable_2="flux_x" />
> </c12:connection>
> <c12:connection component_1="substance_y" component_2="reaction_a_x_y">
> <variable_ref variable_1="concentration" variable_2="concentration_y" />
> <variable_ref variable_1="flux" variable_2="flux_y" />
> </c12:connection>
>
> <c12:connection component_1="substance_a" component_2="abxy_system">
> <variable_ref variable_1="concentration" variable_2="concentration_a" />
> <variable_ref variable_1="flux" variable_2="flux_a" />
> </c12:connection>
> <c12:connection component_1="substance_b" component_2="abxy_system">
> <variable_ref variable_1="concentration" variable_2="concentration_b" />
> <variable_ref variable_1="flux" variable_2="flux_b" />
> </c12:connection>
> <c12:connection component_1="substance_x" component_2="abxy_system">
> <variable_ref variable_1="concentration" variable_2="concentration_x" />
> <variable_ref variable_1="flux" variable_2="flux_x" />
> </c12:connection>
> <c12:connection component_1="substance_y" component_2="abxy_system">
> <variable_ref variable_1="concentration" variable_2="concentration_y" />
> <variable_ref variable_1="flux" variable_2="flux_y" />
> </c12:connection>
>
> <c12:encapsulation>
> <component_ref component="abxy_system">
> <component_ref component="substance_a"/>
> <component_ref component="substance_b"/>
> <component_ref component="substance_x"/>
> <component_ref component="substance_y"/>
> <component_ref component="reaction_a_b_x"/>
> <component_ref component="reaction_a_x_y"/>
> </component_ref>
> </c12:encapsulation>
>
> <!-- Units would also be defined here, as in CellML 1.1... -->
> </model>
>
> _______________________________________________
> cellml-discussion mailing list
> cellml-discussion at cellml.org
> http://www.cellml.org/mailman/listinfo/cellml-discussion
>



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