[go] Re: regulation of cell cycle vs. regulation of progression through cell cycle

[Kimberly Van Auken]

Hi--

In the course of going through our annotations, I've come across cases 
that doesn't seem to work for change #4, if I understand
it correctly.

4) Moving 'cell cycle switching, mitotic to meiotic cell cycle' to be an 
is_a 'positive regulation of meiotic cell cycle' and an is_a
'negative regulation of mitotic cell cycle'. We think that the last two 
terms were why 'regulation of cell cycle' and 'regulation of progression 
through cell cycle' were originally created as distinct terms. However, 
the movement of these as in 3 and 4 makes more logical sense since the 
process they describe stops (negatively regulates) one type of cell 
cycle and initiates (positively regulates)
another.

As an example, we have a gene, glp-1, that regulates the decision 
between mitosis and meiosis in the germ line.  glp-1 could be
annotated to 'germline cell cycle switching, mitotic to meiotic cell 
cycle', but its role in this process is as a positive regulator of
the mitotic cell cycle and a negative regulator of the meiotic cell 
cycle.  This is opposite to what is proposed above.

One alternative is to make the cell cycle switching terms is_a children 
of regulation of mitotic cell cycle and regulation of
meiotic cell cycle, but then we lose the directionality of the 
regulation.  In that case we'd could additionally annotate to the
respective positive and negative regulation terms that could also be 
is_a children of the regulation parent.  Or, we could
make positive and negative regulation terms for cell cycle switching to 
capture the appropriate directionality.  glp-1 would then
be annotated to negative regulation of germline cell cycle switching, 
mitotic to meiotic cell cycle.  I would also then annotate
glp-1 to positive regulation of cell proliferation, which is not related 
to the cell cycle terms in GO, I believe.

--Kimberly


Tanya Berardini wrote:

> Hi Eurie and Val,
>
> Answers are interspersed below:
>
> Eurie Hong wrote:
>
>> I have a couple of questions -
>>
>> Are the "regulation of cell cycle" and "regulation of progression 
>> through cell cycle" going to be specific for just regulating the rate 
>> at which the progression through the cell cycle occurs?  
>
>
> Not just the rate.  The standard definition of 'regulation of xxx' is:
>
> Any process that modulates the frequency, rate or extent of process, 
> [definition of process].
>
> Since the cell cycle is defined as the progression... then the 
> regulation of the cell cycle would be anything that modulates the 
> frequency, rate or extent of the progression.
>
> Then maybe they
>
>> should be renamed "regulation of cell cycle phase" (cell cycle phase 
>> is GO:0022403)?
>
>
> No, that would be a different term, because there are cell cycle phase 
> terms in the ontology (see all children of 'cell cycle phase').  So 
> the regulation of a cell cycle phase would describe the regulation of 
> one of these, for example, 'regulation of interphase' (which doesn't 
> yet exist).
>
>>
>> Or do we need to keep the structure of the regulation terms to mimic 
>> how the cell cycle branch is organized?
>>
>> "regulation of cell cycle" - general grouping term for both 
>> molecular/cellular events and temporal phasing
>> -- "regulation of cell cycle processes" - grouping term for all the 
>> regulation of processes
>> ---- "regulation of cell cycle phase" - specific for going through 
>> the temporal phases
>
>
> Yes.  Our goal is to create regulates terms that don't conflict with 
> the structure of the process ontology.  Right now, we're not creating 
> all of these terms but if and when they are needed, we should be able 
> to insert them easily because the structure already exists.
>
>> The mitotic - meiotic switch terms sound ok.  As long as there are 
>> synonyms to find them - most folks in the field do refer to "entry 
>> into meiosis" but there are positive and negative regulators of the 
>> process.
>
>
> Since we're not proposing changing the terms, synonyms or textual 
> definitions but rather their locations in the graph, if there are 
> synonyms that are missing, please let us know.
>
> Now, on to Val's comments.
>
>
>> On Dec 6, 2007, at 6:25 AM, Valerie Wood wrote:
>>
>
>>> At first glance, I think that what you propsed is OK. You are 
>>> correct that the seperate terms were created to cope with the 
>>> switching between mitotic and meiotic cell-cycles, but your solution 
>>> of making these positive and negative regulatory terms respectively 
>>> seems logically consistant.
>>
>
> Great!  We assume this means that our proposed changes 1-4 are ok.
>
>>>
>>> I think however, there is a more fundamental problem in this portion 
>>> of the graph in that there is some confusion between  the concurrent 
>>> use of meiosis to describe 'meiotic division' and meiosis as a 
>>> 'developmental stage'
>>
>
> From its current placement in the graph, meiosis is a type of cell 
> cycle phase.  It is not restricted to simply meiotic division.
>
>>> I'm not sure if the terms created to cope with the switching between 
>>> mitotic and meiotic cell-cycles rather refer to a switch between 
>>> developmental stage
>>> for example "entry into meiosis" for yeast would include response to 
>>> pheromone, and conjugation etc, and gene products annotated to these 
>>> terms would not necessarily be considered be a 'cell-cycle ' genes.
>>
>
> It seems that a problem here is that 'regulation of cell cycle' is_a 
> 'cell cycle process.'  If we remove this relationship, then 
> 'regulation of cell cycle' will only have a regulates relationship 
> with 'cell cycle' and will not be a cell cycle process.
>
> If we adopt our proposal and remove this relationship, genes annotated 
> to the terms 'cell cycle switching, mitotic to meiotic cell cycle' and 
> 'cell cycle switching, meiotic to mitotic cell cycle' will be involved 
> in regulation of the cell cycle and will not necessarily be annotated 
> to terms that are part_of or is_a children of 'cell cycle.'
>
>>> current child terms of "meiosis"  also include
>>> megasporogenesis (synonym megaspore development ) and these terms do 
>>> not appear to be referring specifically to meiosis as a cell cycle 
>>> process.
>>
>
> Megasporogenesis, despite the name, does not refer to the genesis of 
> the megaspore but specifically to the meiosis of the diploid 
> megasporocyte to give rise to four haploid megaspores.
>
>>>
>>> This is essentially what I was trying to describe in
>>> SF 1831804 ] yeast meiotic development.
>>>
>>> Even some of the definitions of these terms seem to merge both 
>>> concepts into a single term.
>>>
>>> It might make sense to tackle both issues at the same time. I'm not 
>>> sure what the solution is....
>>
>
> While a valid concern, this is not immediately relevant to our current 
> project of cleaning up the ontology for implementation of the 
> regulates relationship.  We will address this issue at a later time.
>
> We are still waiting to hear back from Kimberly who is also looking at 
> their annotations to these terms.  If no other conflicts arise, we 
> look forward to making the changes on Dec. 10th.
>
> Thank you both for your comments.  Please let us know if we didn't 
> address your issues satisfactorily.
>
> Tanya and David
>
>>> Val
>>>
>>>
>>>
>>>
>>> Tanya Berardini wrote:
>>>
>>>> Dear GO Consortium,
>>>>
>>>> As part of the 'regulates' project, we have come across a set of terms
>>>> in the cell cycle portion of the graph that seem problematic. We are
>>>> writing because we know that a lot of previous work has gone into this
>>>> part of the graph and want to be sure that our plan makes sense. We 
>>>> have
>>>> two sets of terms similar to these:
>>>>
>>>> term: regulation of cell cycle (simple term)
>>>> def:A cell cycle process that modulates the rate, extent or mode of 
>>>> the
>>>> cell cycle.
>>>>
>>>> term: regulation of progression through cell cycle (progression term)
>>>> def: Any process that modulates the rate or extent of progression
>>>> through the cell cycle.
>>>>
>>>> Our question is how does 'regulation of progression through cell 
>>>> cycle'
>>>> differ from 'regulation of cell cycle'?
>>>>
>>>> Note that 'cell cycle' itself is defined as "the progression of 
>>>> ...phases and events ...", implying that regulation of the cell 
>>>> cycle is regulation of progression through the cycle; the same 
>>>> holds for the types of cell cycle (i.e. its is_a children).
>>>>
>>>> cell cycle: The progression of biochemical and morphological phases 
>>>> and
>>>> events that occur in a cell during successive cell replication or
>>>> nuclear replication events. Canonically, the cell cycle comprises the
>>>> replication and segregation of genetic material followed by the 
>>>> division
>>>> of the cell, but in endocycles or syncytial cells nuclear 
>>>> replication or
>>>> nuclear division may not be followed by cell division.
>>>>
>>>> If they are indeed describing the same processes, the 'regulation 
>>>> of %'
>>>> and 'regulation of progression of %' terms should be merged. If not,
>>>> then we need to create a bona-fide biological process called
>>>> 'progression through cell cycle' and we need to differentiate that 
>>>> from
>>>> 'cell cycle' with a really good definition. Currently the progression
>>>> terms are only used in conjunction with regulation.
>>>>
>>>> The way we represent these in the graph is also inconsistent. An 
>>>> example
>>>> follows:
>>>>
>>>> Case 1: No direct link between the 'regulation of progression through
>>>> cell cycle' term and 'cell cycle' term exists.
>>>>
>>>> regulation of cell cycle
>>>> --[i]regulation of progression through cell cycle
>>>>
>>>>
>>>> Case 2: Direct link between 'regulation of progression through meiotic
>>>> cell cycle' and 'meiotic cell cycle' exists.
>>>>
>>>> regulation of meiotic cell cycle
>>>> --[i]regulation of progression through meiotic cell cycle
>>>>
>>>> meiotic cell cycle
>>>> --[p]regulation of progression through meiotic cell cycle
>>>>
>>>>
>>>> We propose:
>>>>
>>>> 1) Merging the 'regulation of progression through' terms
>>>> with their simpler parents when they exist.
>>>>
>>>> 2) Renaming the 'regulation of progression through' terms to their
>>>> simpler forms when the simpler parents do not exist since the parent
>>>> non-regulates terms are already defined as the progression of...
>>>>
>>>> 3) Moving 'cell cycle switching, meiotic to mitotic cell cycle' to
>>>> become an is_a 'negative regulation of meiotic cell cycle' and an is_a
>>>> 'positive regulation of mitotic cell cycle'.
>>>>
>>>> 4) Moving 'cell cycle switching, mitotic to meiotic cell cycle'
>>>> to be an is_a 'positive regulation of meiotic cell cycle' and an is_a
>>>> 'negative regulation of mitotic cell cycle'. We think that the last 
>>>> two
>>>> terms were why 'regulation of cell cycle' and 'regulation of 
>>>> progression through cell cycle' were originally created as distinct 
>>>> terms. However, the movement of these as in 3 and 4 makes more 
>>>> logical sense since the process they describe stops (negatively 
>>>> regulates) one type of cell cycle and initiates (positively regulates)
>>>> another.
>>>>
>