PAMGO-2007 Topics for Discussion

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Candace - 6/26/07

Magdalen's interpretation of Candace's trees (with conference call comments incorporated)

New terms are evident by their lack of assigned numbers. Those to be obsoleted are indicated by [obsolete]

TREE I: GO:0008219 : cell death [4946]

     GO:0012501 : programmed cell death
          GO:0055045 : antipodal cell degeneration 
          GO:0006915 : apoptosis
          GO:0048102 : autophagic cell death
          GO:0035234 : germ cell programmed cell death
          GO:0010421 : hydrogen peroxide-mediated programmed cell death
          GO:0009626 : hypersensitive response [obsolete]
                 GO:0010363 : regulation of hypersensitive response[obsolete]
          GO:xxxx : Host programmed cell death induced by symbiont
                 GO:xxxx : Programmed cell death via plant hypersensitive response
                        GO: xxxx: Regulation of plant hypersensitive response
                                 GO:xxxx: Negative regulation of…
                                 GO:xxxx: Positive regulation of….
          GO:xxxxx: oncosis
          GO:xxxxx: pyroptosis
          GO:0035096 : larval midgut cell programmed cell death
          GO:0016244 : non-apoptotic programmed cell death 
          GO:0043067 : regulation of programmed cell death 
          GO:0046666 : retinal cell programmed cell death
          GO:0010343 : singlet oxygen-mediated programmed cell death 
          GO:0010198 : synergid death

TREE II: GO:0044003 : modification by symbiont of host morphology or physiology

     GO:0052040 : modulation by symbiont of host programmed cell death 
          GO:0052150 : modulation by symbiont of host apoptosis
          GO:0052152 : modulation by symbiont of host non-apoptotic PCD 
          GO:0052041 : negative regulation by symbiont of host PCD
          GO:0052042 : positive regulation by symbiont of host PCD
     GO: xxxxx : Modulation by symbiont of host defense-related programmed cell death
          GO:xxxx : negative regulation by symbiont of host defense-related PCD
          GO:xxxx : positive regulation by symbiont of host defense-related PCD

Hypersensitive Response and the PCD tree

I’d like to see if we can bring the long, wide-ranging discussion about HR and programmed cell death to a conclusion that will be satisfactory to everyone. I have just re-read the discussion on the PAMGO wiki and also the 24-page word document that I have that collected a long email discussion on this topic among me, Alex Diehl, Chris Mungall, Michelle, and Amelia – mostly in the summer and fall of 2005. (If anyone would like to read through that, I’m happy to send it.)

I. Part of this topic is related to the “response to” and “defense response to” terms, most of which are children of “GO:0051704 - multi-organism process” but not “GO:0044419 - interspecies interaction between organisms”. Some of these terms are ones like “response to bacterium” or “defense response to bacterium” and clearly (by their defns) involve interspecies interaction between organisms, so whether they will eventually have to become children also under “GO:0044419 - interspecies interaction between organisms” is a question to be addressed sometime.

This relates directly to the question of how to handle the term currently in GO –“hypersensitive response”, which several have written to say they would like to keep because it is one specific form of programmed cell death. It is currently a child of “programmed cell death”, so that makes sense. Its current defn is “The rapid death of plant cells in response to invasion by a pathogen.” This clearly indicates that there is an interaction between 2 organisms (usually of different specieis), so whether it can stay where it is now (not currently under “interspecies interaction between organisms”) and also exist under “interspecies interaction between organisms” will have to be resolved along with the terms mentioned above. But, for now, it seems that it would be useful to modify the defs of these terms to make it more clear that they should be used to annotate genes of the “host” rather than the organism inducing the response, if there are 2 organisms involved (and such a change was suggested by Trudy/Michelle/Candace on the wiki). Finally, the case has been made for a new term in between PCD and HR, which seems to make sense, as it could be used to cover situations as the squid example offered by Marcus on the wiki. So, I suggest the following for this section:

ACTION ITEM 1: After the def of “GO:0012501 – programmed cell death,” add the following “COMMENT: This GO term should be used to annotate genes in the organism undergoing the PCD. For annotating genes in another organism whose products modulate PCD in a host organism, see “GO: 0052040 - modulation by symbiont of host PCD.”

ACTION ITEM 2: Create a new, child term for GO:0012501 – programmed cell death = “GO:xxxxxxx = host programmed cell death induced by symbiont.” Definition = “Cell death in a host resulting from activation of host endogenous cellular processes after direct or indirect interaction with a symbiont. An example of direct interaction is penetration by hyphae, and of indirect interaction is encountering symbiont-secreted molecules. COMMENT: This GO term is to be used to annotate gene products in the host, not the symbiont. For the corresponding term to use for annotating gene products in the symbiont that induce PCD in the host, see GO: 0052044 - induction by symbiont of host PCD.”

ACTION ITEM 3: Make obsolete the GO term “GO:0009626 – hypersensitive response” and replace it with GO:xxxxxxx, “plant hypersensitive response.” (Or, possibly, “programmed cell death via plant hypersensitive response,” as suggested by Jane on the wiki – what do others think?) [All gene products currently annotated to HR could be transferred to this new term –it’s the same think, just more explicit). Definition (slightly modified from original]: “the rapid, localized death of plant cells in response to invasion by a pathogen. COMMENT: This GO term is to be used to annotate gene products in the plant. For the corresponding term to use for annotating gene products in the symbiont that induce HR in the plant, see “GO: xxxxxxx – modulation by symbiont of host defense-related programmed cell death.” [new term – see below] Add synonyms - exact: HR; HR-PCD

ACTION ITEM 4: For GO:0010363 – regulation of hypersensitive response, change def slightly (for clarification – will not change meaning) to “ any endogenous process that modulates the frequency, rate or extent of the plant hypersensitive response.” Add NOTE: “See, alternatively, GO:0052040 : modulation by symbiont of host programmed cell death.”

ACTION ITEM 5: Add new children terms to GO:0010363 – regulation of hypersensitive response:

  a) negative regulation of hypersensitive response  

synonyms - exact: negative regulation of HR; negative regulation of HR-PCD definition: “Any endogenous process that stops, prevents or reduces the frequency, rate or extent of the hypersensitive response in a plant.”

  b) positive regulation of hypersensitive response  

synonyms - exact: positive regulation of HR; positive regulation of HR-PCD definition: “Any endogenous process that activates, maintains or increases the frequency, rate or extent of the hypersensitive response in a plant.”


II. That brings us to the PCD-related terms under the “interspecies interaction between organisms” tree, and whether there is a need for a “defense-related PCD” that would essentially be synonymous with the HR in plants (at least from everything I’ve read). Several people (including Donghui Li) have pointed out on the wiki and in previous discussions that the HR is one type of PCD. Most authors that give a definition of the HR in plants say something like “a defense response involving rapid, localized cell death that functions to limit pathogen growth,” or “a rapid, localized, defense-associated PCD). Since many people that work on plant-pathogen interactions would most likely search for a HR- or PCD-related term under general host defense responses, I now have come around to agreeing with others that a specific term related to defense-related PCD (=HR in plants) would be useful. (Right now there is no term related to PCD under the PAMGO term “modulation by symbiont of host defense response,” where I think many would look.) So, I am proposing that a new GO term be created:

ACTION ITEM 6A: Create new term “GO:xxxxxxx = modulation by symbiont of host defense-related programmed cell death”

   Definition =  Any process by which an organism modulates the frequency, rate or extent of defense-related programmed cell death in the host organism. The host is defined as the larger of the organisms involved in a symbiotic interaction. COMMENT: This term is used to annotate gene products of the symbiont; see also “GO:0009626 : hypersensitive response ” [or new term] to annotate host genes.
  Synonyms:  exact – modulation by symbiont of plant hypersensitive response;  -- of plant HR
  This new term would be a child term to “GO:0052040 : modulation by symbiont of host programmed cell death” AND “GO:0052031 : modulation by symbiont of host defense response.”

ACTION ITEM 6B: Create four new terms as children to new term described above (6A). the resulting tree would be as shown below, and parallels similar tree under GO:0052040 – modulation by symbiont of host programmed cell death:

    GO:xxxxxxx – modulation by symbiont of host defense-related programmed cell death

GO:xxxxxxx – negative regulation by symbiont of host defense-related PCD GO:xxxxxxx – positive regulation by symbiont of host defense-related PCD GO:xxxxxxxxx – induction by symbiont of host defense-related PCD GO:xxxxxxxxx – upregulation by symbiont of host defense-related PCD

1) :xxxxxxx – negative regulation by symbiont of host defense-related PCD Definition: Any process by which an organism stops, prevents or reduces the frequency, rate or extent of defense-related programmed cell death in the host organism. The host is defined as the larger of the organisms involved in a symbiotic interaction. COMMENT: This term is used to annotate gene products of the symbiont; see also “GO:xxxxxxx – negative regulation of hypersensitive response ” [new term] to annotate host genes. Synonyms: narrow = suppression by symbiont of host defense-related PCD exact = negative regulation by symbiont of plant HR exact = negative regulation by symbiont of plant hypersensitive response narrow = inhibition by symbiont of host defense-related PCD exact = down regulation by symbiont of host defense-related PCD exact = down-regulation by symbiont of host defense-related PCD exact = downregulation by symbiont of host defense-related PCD exact: inhibition of host defense-related PCD narrow: inhibition of HR narrow: inhibition of hypersensitive response narrow: suppression of HR

2) :xxxxxxx – positive regulation by symbiont of host defense-related PCD Definition: Any process by which an organism activates, maintains or increases the frequency, rate or extent of defense-related programmed cell death in the host organism. The host is defined as the larger of the organisms involved in a symbiotic interaction. COMMENT: This term is used to annotate gene products of the symbiont; see also “GO:xxxxxxx – positive regulation of hypersensitive response ” [new term] to annotate host genes. Synonyms: narrow = activation by symbiont of host defense-related PCD narrow = stimulation by symbiont of host defense-related PCD exact = enhancement by symbiont of host defense-related PCD exact = positive regulation by symbiont of plant HR exact = positive regulation by symbiont of plant hypersensitive response narrow: activation of HR narrow: activation of hypersensitive response

3) GO:xxxxxxxxx – induction by symbiont of host defense-related PCD Definition: The activation by an organism of defense-related programmed cell death in the host organism. The host is defined as the larger of the organisms involved in a symbiotic interaction. COMMENT: This term is used to annotate gene products of the symbiont; see also “GO:xxxxxxx – positive regulation of hypersensitive response ” [new term] to annotate host genes. Synonyms: exact = activation by symbiont of host defense-related programmed cell death exact = activation by symbiont of HR exact = induction by symbiont of HR exact = induction by symbiont of hypersensitive response exact = induction of HR

4) GO:xxxxxxxxx – upregulation by symbiont of host defense-related PCD Definition: Any process by which an organism increases the frequency, rate or extent of defense-related programmed cell death in the host organism. The host is defined as the larger of the organisms involved in a symbiotic interaction. COMMENT: This term is used to annotate gene products of the symbiont; see also “GO:xxxxxxx – positive regulation of hypersensitive response ” [new term] to annotate host genes. Synonyms: exact = enhancement by symbiont of host defense-related PCD exact = upregulation by symbiont of HR exact = upregulation by symbiont of hypersensitive response exact = upregulation of HR exact = enhancement of HR

ACTION ITEM 7: Correct “exact synonym” for GO:0052042 - positive regulation by symbiont of host programmed cell death”: FROM: “enhancement or induction of host programmed cell death” [“induction of….” is an existing GO child term to this one] TO: “enhancement of host programmed cell death”


Other terms mainly from the “animal world” added to the PCD tree

Proposal: to add three new terms and to modify four terms that currently exist; also, slightly rearrange the “programmed cell death” tree to the following:


programmed cell death

----apoptosis ----non-apoptotic programmed cell death (most likely should be obsoleted) ----autophagic cell death (would become sibling to “apoptosis” etc.) ----oncosis (new term) (would become sibling to “apoptosis” etc.) ----pyroptosis (new term) (would become sibling to “apoptosis” etc.) ---- host programmed cell death induced by symbiont (new term) ---- hypersensitive response-related death in plants (modified term)

1) New term – “Oncosis” Definition: “a proinflammatory pathway leading to cell death accompanied by cellular and organelle swelling and increased membrane permeability [source:GOC:cwc, PMID:15784530; PMID:1579367]”

Add narrow synonyms: “necrotic cell death” and “necrosis”

If the GO term “non-apoptotic programmed cell death” is merged with its parent, “programmed cell death” (PCD) (see below), then this new term would be made a child of PCD and a sibling to GO term “apoptosis”

2) New term – “Pyroptosis” Definition: “a cell death pathway resulting from caspase-1 activity leading to plasma membrane breakdown and proinflammatory cytokine release [source:GOC:cwc, PMID:15784530; PMID:17599095; PMID:11303500]”

Add narrow synonyms: “necrotic cell death” and “necrosis”

If the GO term “non-apoptotic programmed cell death” is merged with its parent, “programmed cell death” (PCD) (see below), then this new term would be made a child of PCD and a sibling to GO term “apoptosis”

(another possible, alternative definition: a caspase-1-dependent programmed cell death that includes membrane breakdown and proinflammatory cytokine processing) [source as above]


3) GO:0006915 – apoptosis Add the following “COMMENT: “This GO term should be used to annotate genes in the organism undergoing the PCD. For annotating genes in another organism whose products modulate PCD in a host organism, see “GO: 0052040 - modulation by symbiont of host PCD.”” Add narrow synonyms: “necrotic cell death” and “apoptotic necrosis”

4) GO:0048102 – autophagic cell death – add one word to the current definition: a non-inflammatory destruction of a cell by its own lysosomal contents. This type of programmed cell death is seen when entire tissues, or parts thereof, are committed to destruction, and occurs by the formation of multiple acidic autophagic vacuoles within the doomed cells. [source: GOC:jic, PMID:11494315] Add synonym: “exact: type II programmed cell death” and “exact: type II cell death” [source: PMID:15784530]

If the GO term “non-apoptotic programmed cell death” is merged with its parent, “programmed cell death” (PCD) (see below), then this current GO term would be made a child of PCD and a sibling to GO term “apoptosis”

5) GO:0016244 – non-apoptotic programmed cell death Midori has suggested that this term is not ontologically desirable and should be obsoleted. I [Candace] have no problem with that, although the term is currently somewhat useful – as described in PMID:15784530, sometimes one can tell that a type of PCD is not apoptotic but not what specific alternative type it is; the authors expect more different types of PCD to be described eventually. That much information [i.e. programmed cell death, but not apoptotic] is actually useful. And, there are currently 24 annotations to it. Alex Diehl has suggested that this term be merged with its parent term (programmed cell death). Alex, “This eliminates the term but preserves the annotations in an ontologically correct manner. Interested parties may go back and re-annotate to one of the new terms if they choose.” [This seems like a good suggestion, and it seconds Midori’s suggestion..

If GO editors decide instead that the term should be kept, then at least

Remove the synonym: “exact: type II programmed cell death” ]

6) GO:0012501 – programmed cell death Add the following “COMMENT: This GO term should be used to annotate genes in the organism undergoing the PCD. For annotating genes in another organism whose products modulate PCD in a host organism, see “GO: 0052040 - modulation by symbiont of host PCD.”


Suggestions made at Nov 15 meeting

Action Item 3 Preference is to use "plant hypersensitive response" instead of "PCD via plant hypersensitive response"

Action item 6B Even though in the general structure of the GO most of the positive regulation terms have "induction.... and "upregulation..... as child terms, it was suggested to make these synonyms of positive regulation by symbiont of host defense-related PCD".