[Obo-relations] Relation between a biological process and a cell

[Chris M. <cj...@fr...>]

I have some questions regarding relations between processes and
continuants, specifically cells. There is some urgency to these questions,
as we are about to embark on the integration of GO biological process with
ontologies of continuants, commencing with the OBO Cell ontology then
moving on to the EBI chemical ontology.

So far, we have two relations that are relevant.

The relation "has_participant" between a process and an object,
defined as follows:

  "P has_participant C if and only if: given any process p that
  instantiates P there is some continuant c, and some time t, such
  that: c instantiates p at t and c participates in p at t"

The definition does not state much in the way of the nature of this
participation.

The paper has the following examples:

  cell transport has_participant cell
  death has_participant organism
  breathing has_participant thorax.

I'm assuming familiarity with the discussion of instance level and
class level relations in the paper.

Our ontology also includes has_agent:

  "As for has_participant, but with the additional condition that the
  component instance is causally active in the relevant process"

Are these two relations enough to define certain GO process classes in
terms of the continuants they involve?

The GO class "T cell proliferation" can be defined using the genus
class "proliferation", with the differentia being the characteristic
of (informally) "operating upon populations of T cells". What should
the formal relation replacing "operating upon populations of" be?

Here is the existing GO, non-computable natural language definition:

 "The rapid expansion of a T cell population by cell division. Follows
  T cell activation."

One could therefore create a relation "acts_on_population_of". Before
doing so, we should consider if an existing relation will suffice, or
if we can come up with a more re-usable relation.

Consider an existing relation: "has_participant" - is this relation
correct to use here; and if it is correct, is it specific enough to
make use to make our definition of "T cell proliferation" unambiguous
to a computer?

Is it correct? Well, every instance of T cell proliferation does
indeed have a T cell as a participant, so the class level definition
is not violated. But it seems the actual participant is the
population, not any one individual cell. Should we create a new
relation (something like "has_participants_from_population_of"), or
should we create an entirely new continuant class "T cell population"
defined in terms of "T cell"?

The latter is logically sound and can be implemented without actually
generating a seperate parallel ontology of aggregate classes by using
anonymous or skolem classes. But I would prefer we kept things simple
and went with a relation between a process and a non-aggregate
continuant.

Secondly, should the relation be more specific? Does it need to state
the nature of the participation - for example, that the population at
time t1 is necessarily the same or lower than the time at t2, where
t2>t1 and t1 and t2 are within the temporal boundaries of the process?
I believe the relation should not state this, since this should be
defined in the class "proliferation".

Another example illustrating the population-instance vs unary-instance
distinction is GO classes relating to "homeostasis". Instances of the
GO process "cell homeostasis" have a single cell as participant. With
"T-cell homeostasis" it is a participation relation between a process
and a population of cells. We cannot state both:

  cell homeostasis   <=> homeostasis, has_participant = cell
  T cell homeostasis <=> homeostasis, has_participant = T cell

Since a reasoner will (erroneously) believe that T cell homeostasis is
a kind of cell homeostasis. We either need to introduce a new
relation, or explicitly represent the concept of aggregates of
continuants.

Let's look at an example illustrating a different principle: cell
differentiation. Clearly the process of cell differentiation has
"cell" as participant. An instance of a cell undergoing
differentiation will instantiate a class C at some time t and a class
C' at some later time t'. The class relation between C' and C is
derives_from, but what about the instance level relation between the
cell and the process? Is it participating at both t and t'
inclusively? Or does it cease participating prior to t'?

Taking a practical example illustrating this, we want to form a
computable definition of "plasmatocye differentiation". The natural
language definition is:

  "The processes by which a hemocyte precursor cell acquires the
  characteristics of the phagocytic blood-cell type, the
  plasmatocyte. Plasmatocytes are a class of arthropod hemocytes
  important in the cellular defense response."

Here, C is "hematocyte precursor" and C' is "phagocyte". The
derives_from relation between the latter and the former is trivially
obtainable (plasmatocyte is_a hemocyte, X derives_from X precursor).

But what is the relation between the process class "plasmatocyte
differentiation" and the continuant class "plasmatocyte"? Is it one of
participation, or do we consider the process of differentiation to be
complete as soon as the plasmatocyte has fully differentiated? If so,
we must choose another relation in place of has_participant.

If we consider it to be a participant, then surely the precursor is
also a participant. In this case our class level relation should
discriminate between these variations of participation (although we
can actually obtain this from the derives_from relation between the
two continuant classes, this is a little awkward)

An analagous example would be "cysteine biosynthesis", which has less
debatable temporal boundaries. Is cysteine a participant in its own
manufacture? If not, what is the appropriate relation to use?

I don't think has_agent is appropriate for any of the above cases -
the agent would be some external factor, cell, reactant.

An example illustrating the agency/non-agency participation
distinction: "neuroblast activation". Here the neuroblast is a
participant in the activation, but without agency (it is the thing
being activated). The activating factor/ligand is the agent. Do we
need an additional relation has_inactive_participant where we
specifically wish to indicate that the role of the participant is
patient?

It seems that agency invokes causation which is difficult.
Fortunately, in the majority of relations we would like to add between
process and cell the active participant can be left implicit.

These examples illustrate the most problematic cases. Below is
what I think is the full list of GO biological processes that have
have some relation to cell or cells that is important to state in the
computable definition. I have marked every class where I think the
relation between the process and the cell is clearly one where the
has_participant relation will be both correct and specific enough.

 * chemotaxis
 differentiation (see above)
   similar classes:
      development
      morphogenesis
      formation
      generation
      germination
 * division
 * degeneration
 * death
 * growth
 homeostasis (see above)
 activation (see above)
 proliferation (see above)
 * maturation
 * migration
 * anchoring           (eg oocyte nucleus anchoring)
 * branching           (eg trichome branching)
 * construction        (eg oocyte construction)
 * elongation          (eg spermatid nuclear elongation)
 * fusion
 * polarization
 * positioning
 * transition           (eg epithelial to mesenchymal transition)
 commitment            (eg cone cell fate commitment)

We will be adding these relations fairly soon, so I'd favour a
solution that would be simple to implement in the short term leaving
open the option for adding extra rigour later.

Cheers
Chris