Cell Cycle Content Meeting follow-up 27 March 2013

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Meeting report

  • Work through comments

Phase terms, TO DO

phase terms relationships to cell cycle events etc

1. The relationship between the phases and other cell cycle processes. David OS has suggested that we could continue to use part_of, or when part_of is too strong use happens_during (also starts_during and ends_during). But I got the sense during the meeting that we wanted to steer away from using part_of between processes and phases and make the phases both is_a and part_of disjoint from the rest of bp? The main part_of children are currently the cell cycle transitions.

PHASE B: add new relationship types happens_during, starts_during, ends_during

see https://sourceforge.net/tracker/index.php?func=detail&aid=3610886&group_id=36855&atid=440764

Chris: Do you mean replace the part_of links between processes 9e.g. transitions) and phases to be 'during' links? I had imagined keeping them as part_of at first. I'd really like to see logical definitions for the transition processes in terms of the phases. This might need a richer set of relations. E.g GO:0000216 ! M/G1 transition of mitotic cell cycle EquivalentTo 'mitotic cell cycle phase transition' and starts_during 'M phase' and ends_during 'G1 phase' see https://sourceforge.net/tracker/?group_id=36855&atid=440764

2. How to handle phases that are also processes. It's possible to frame some phases as processes, indeed some phases are defined this way e.g. metaphase. Would we want these to be represented under both 'cell cycle phase' and 'cell cycle process' and have two separate terms? Or do we decide which should be phases and which should be processes and just split them up?

 mitosis and meiosis will no longer be cell cycle phases 

3. Do we want to make this node generic for all phases in GO, and use it to house some of the e.g. developmental phases there? How might that look e.g.:

* biological process
** [i] cell cycle phase
*** [i] developmental phase, etc

4. Are we going to obsolete the "regulation of phase terms" (cleaner) (DONE)

5. Reword the phase definitions so that it would not make sense logically for the regulation of transitions to be part_of children of phases (this depends on the outcome of 5 but the phase defs are a bit inconsistent)

 TO DO: Jane to revisit definition of phases and make them sound less process-y and more phase-y 


mitosis and meiosis I & II

  • outstanding question: although this is currently a little odd, because although mitosis has a nuclear division parent, meiosis meiosis I and meiosis II don't....maybe the meiosis terms are a little broader and encompass MORE than nuclear division ? although maybe this is confusion between a "meiotic cell cycle" and "meiosis".... I'm not sure.....anyone else know?
  meiosis I and meiosis II should both have a nuclear division parent 
  • follow up to Q above: OK meiosis is "a specialised type of nuclear division" so it should also have this parent (I'll ask Midori if there is a reason why it doesn't). When people refer to "meiosis" in the broader sense, they are really talking about the meiotic cell cycle, or meiotic development (i.e which would include sporulation in fission yeast). We should probably define meiosis and mitosis as a type of nuclear division (qualified by the cell cycle in which it takes place (meiotic or mitotic). each should have 2 parents the "x cell cycle" & "nuclear division". I'm struggling with meiosis I and meiosis II, because if these are the specialised nuclear divisions there are lots of child processes which are not part of nuclear division (DNA replication processes and the G2/M transition for example). It seems as though we need a term which represent to represent all of the events which occur (meiosis I + interphase) ......I have not seen such phrases used ........and I haven't managed to find anything yet....?

(Midori thinks the omission was just an omission)

  • more follow up: OK it sounds as though we need to add these "nuclear division" parents, and then find a way to represent "meiosis I cell cycle process" and "meiosis II cell cycle process" (maybe that is the way?) to capture all the events which happen during interphase AND meiosis of those specific divisions, and then move the existing children of meiosis I & II to these new parent terms where appropriate (obviously the events which are analogous to the mitotic events can stay under the Meiosis I and meiosis II terms). Would that work?
 meiosis I = everything that happens during meiosis I, do we need 'nuclear division involved in meiosis I'? 
 David to consult meiosis experts 


Transitions TO DO

Question from Val:

I think we might have a problem with the G1/S transition def (for pombe, it seems a little specific. and it doesn't really match the G2/M definition if it is only describing the switch itself should be more like:

The mitotic cell cycle transition by which a cell in G1 commits to S phase. The process begins when the kinase activity of G1 cyclin-dependent kinase (G1 CDK), reaches a threshold high enough for the cell cycle to proceed. This is accomplished by activating a positive feedback loop that results in the accumulation of unphosphorylated and active G1 cyclin-dependent kinase (G1 CDK).

The way I understood the discussion

1. The CDK cyclin complex activation was the  transition (i.e a switch) so this process is actually a single molecular event 
(activation of the CDK, and the only things which should be annotated to the transition itself were CDK and the cyclin
2. There are numerous ways the switches can be positively  and negatively regulated


i) CDK itself positively regulates G/M transcription of Cyclins (via MBF) as part of +ve feedback loop

ii) CDK negatively regulates transition by inhibiiton of SIC1 G2/M

i) CDK itself positively regulates G/M transcription of Cyclins as part of +ve feedback loop (NOT In pombe)

ii) cdc25 (and any upstream activators of) positively regulates transition via dephosphorylation

iii) wee1 and any upstream activators of negatively regulate via phosphorylation

Can anyone confirm this or correct me? If no one is sure, I will check with the experts (vw: not yet done)

 Val will look at definitions again.  Definitions seemed very clear and agreed to during meeting. 

Checkpoints TO DO

All the discussion and resolution here previously is covered in these items https://sourceforge.net/tracker/?func=detail&aid=3610889&group_id=36855&atid=440764 https://sourceforge.net/tracker/?func=detail&aid=3610890&group_id=36855&atid=440764

  • Regulation between checkpoint signaling and checkpoint response (signaling is_a positive regulation of response?)
    • We think the checkpoint positively regulates the response - put in, and Val checking with Rob


  • Regulation between checkpoint signaling and phase transition (signaling is_a negative regulation of phase transition?)
    • we think checkpoint again - put in, and Val checking with Rob
  • Regulation between checkpoint and phase transition (checkpoint is_a negative regulation of phase transition?)


 make sure that %checkpoint positively regulates %checkpoint response for all checkpoints 
      use 'by' ? positive regulation of apoptosis *by* DNA damage checkpoint
 reconvene at GO meeting 

negative regulation of Checkpoints

The only *known* negative regulation so far is DNA damage checkpoint https://sourceforge.net/tracker/?func=detail&aid=3608141&group_id=36855&atid=440764 a suggestion, should we obsolete the other terms, they could be re-instated if this type of regulation is found to exist?

Response from Jane : I actually just added these regulation terms so I could merge 'regulation of G1/S transition checkpoint' etc into them (if you remember we decided to do away with the checkpoints classified only by the phase).So I don't have specific examples - we could add this to the obsolete list but perhaps we want to run it by the experts? Are the other regulation of checkpoints terms valid (i.e. regulation and positive regulation?)

Further question from Val : We have only decribed detection, and the signalling pathway. I am not sure how "positive regulation " would fit in here....I'm not sure that this is needed (unless it is detection).....D/T what do you think?

General SOP for annotation overhauls

Dealing with merges/ obsoletions etc

SF tickets

  • regulation of CDK activity [1]