GO Content Meeting Notes Aug 22, 2004
Carnegie, Stanford, CA

Jane Lomax (EBI-GO), Sue Rhee (TAIR), Amelia Ireland (EBI-GO), Alex Diehl (MGI),
David Hill (MGI), Gopal Gopinathrao (Reactome),  Suzi Lewis (BDGP), Michael Ashburner
(University of Cambridge, UK), Candace Collmer (Wells College, PAMGO), Suparna
Mundodi (TAIR),  Michelle Gwinn Giglio (TIGR), Jennifer Clark (EBI-GO), Val Wood
(Sanger), Midori Harris (EBI-GO), Judy Blake (MGI), John Day-Richter (BDGP),
Shauna Somerville (Carnegie Institution), Alan Collmer (Cornell University, PAMGO),
Peifen Zhang (TAIR), Eurie Hong (SGD), Peter Karp (MetaCyc), Rob Nash (SGD), Hartmut
Foerster (TAIR), Tanya Berardini (TAIR).

Contents

Minutes:
    Pathogenesis
    Cell Killing
    Metabolism
    Cell cycle
    Component
    
Appendices:
    1. Action items
    2. Agenda.
    3. Background reading from Jane on all three topics.
    4. The pre-meeting PAMGO obo file.
    5. Alex Diehl's pre-meeting proposal on pathogenic terms (sourceforge url).
    6. Alex Diehl's pre-meeting proposal on Cell Killing terms (url).
    7. Comments from Matt Berriman on the pathogenesis proposals.
    8. Pathogenesis powerpoint presentation.
    9. PAMGO powerpoint presentation.
    10. Metabolism explanation powerpoint presentation.
    11. Metabolism proposal powerpoint presentation.
    12. Cell Cycle powerpoint presentation.
    13. Alex's proposal: Pathogenic Terms I want to change or eliminate from the GO.
    14. Alex's Cell Killing Proposal and Terms
    15. Alex's Cell Killing Terms incorporating the discussion at the GO Content meeting
    16. Suparna's proposal on host-pathogen interactions. (url)


--------------------------------------------------------------------------------

MINUTES


Purpose of the meeting: To bring together GO group members and a few domain experts
in person. To review and discuss three problematic areas in the GO process ontology;
metabolism, pathogenesis, and cell cycle; in order to come up with acceptable solutions
and specific action items to resolve the problems.

Various proposals for change have been submitted and these are included in the appendix
sections. A summary is included in the appendix called: 'Background reading from Jane on
all three topics.'

The first topic involved improvements to the terms around 'host-pathogen interaction'.
As a consequence of this we discussed the definition of pathogenesis, but we also
discussed in some depth the ways of defining situations where two organisms have
physiological interaction. (e.g. parasitic relationships, and symbiotic relationships.)



Pathogenesis and interactions between organisms.
===============================================

See also the appendices:
Background Reading From Jane On All Three Topics
Alex Diehl's Pre-Meeting Proposal On Pathogenic Terms
Comments From Matt Berriman On The Pathogenesis Proposals
Pathogenesis Powerpoint Presentation.    
PAMGO Powerpoint Presentation.    
Alex's Proposal On Pathogenic Terms To Change Or Eliminate From The GO
Suparna's Proposal On Host-Pathogen Interactions. (Url)    


Problems to be addressed:

Problem I: Intelligibility
The meaning of 'pathogenesis' is unclear from the name. It should be used for pathogen
annotations only, but, from AmiGO we find that there are currently annotated: 5 human
gene products, 5 mouse, 1 rat.

Problem II: True path
Terms specific for viral proteins have incorrect ancestry. This violates the true path,
and creates odd GO slims.

Problem III: Which organism?
'Cytolysis' can occur by multiple mechanisms e.g. as a result of exposure to a exogenous
toxin, or by the immune system to destroy an infected cell. Therefore two completely
different processes would be annotated to the same term. There is a problem of
univocity, which means that terms should mean the same wherever they're used.

Problem IV: Symbiosis
Interactions between symbiont and host may be destructive to host (parasitism), they may
also be mutualistic or commensalistic. No terms in GO currently cover these processes.
Biological processes to establish these states (symbiosis or parasitism) often conserved
so common terms will be needed to cover the same processes within different types of
relationships (e.g. the initiation of pathogenesis versus the initiation of mutualism
by a microbe both have some processes in common, and it would be helpful to be able
to see this through GO terms and tree structure).

Discussion of symbiosis     
======================
from Jane's Pathogenesis presentation:
(ftp://ftp.geneontology.org/pub/go/meeting/minutes/20040822_Stanford_Content/pathogenesis.pdf
ftp://ftp.geneontology.org/pub/go/meeting/minutes/20040822_Stanford_Content/pathogenesis.ppt)


There was some discussion about how, on one hand, PAMGO really wanted general
terms for processes that could apply to organisms involved in either pathogenesis or
symbiosis (because seeing these common processes across different end results would
be really useful). Others at the meeting, really wanted the terms
under the separate processes of pathogenesis and symbiosis, because people who wanted to
use GO to annotate genes in pathogens or symbionts would naturally tend to search
using those familiar categories.  In the end, we came up with a compromise.  We would
make, as children, under the parent term "interaction between host and other organism",
all of the general terms as proposed by PAMGO (e.g. "recognition of host" etc.), but
other children under that parent term would also be "pathogenesis" and "symbiosis", and
children under each of these would include the general terms as specified for those
processes (e.g. under "pathogenesis" you would have the child term "recognition of host
during pathogenesis", and under "symbiosis" you would have "recognition of host during
symbiosis."  In addition, under the general term "recognition of host" you would find
the children "recognition of host during pathogenesis" and "recognition of host during
symbiosis." That should allow the needs of all to be met.

Action 1. Establish common parents and replicate subtrees for symbionts and pathogens as
appropriate, e.g.
      
            [i]acquisition of nutrients from host
            ---[i]acquisition of nutrients from host during symbiosis
            ---[i]acquisition of  nutrients from host during pathogenesis

We discussed the difficulties in referring to, and in defining, the partners in the
symbiotic and parasitic relationships.

It is difficult to define symbioses. They may be mutualistic or commensalistic. There
are no terms in GO to cover these processes. The biological processes to establish
these states are often conserved so common terms are needed for the various types of
symbioses. Does symbiosis include pathogenesis (and therefore parasitism)?  This
problem of exactly what "symbiosis" means seems to exist across biology - where it
is used differently by different texts, people, etc. The way it is used below, and
the way PAMGO thought about it when they were working on their tree, is that "symbiosis"
does not include "pathogenesis" or parasitism", but only mutualism and commensalism
- i.e. when one or both organisms benefits, but neither is harmed. It seems that it
is important to get this matter of how we are using "symbiosis" in GO straightened out.
Should PAMGO define symbiosis to exclude parasitism or pathogenesis in their modified
proposal?

Action 2. Should PAMGO define symbiosis to exclude parasitism or pathogenesis in their
modified proposal? This remains a point for further discussion.

We considered how to define 'host'. PAMGO suggest that it is an organism from which
another organism obtains nutrition, shelter, dispersal, protection etc. Although
this does describe a host accurately, it could also apply
equally well to either individual in a mutualistic relationship in which
neither organism would be called a host.
 
Action 3. Define host based on PAMGO definition (To be taken from:
% interaction with host organism
Def: any interaction between an organism, usually a parasite or symbiont, and another
organism from which it may obtain nourishment, protection, and/or a means of dispersal.

Action 4. We need a name and a definition for the 'hostee'; the dependent organism in a
relationship, e.g. a parasite.    
    
Action 5. Remove 'interaction with non-host organism' and move sub-terms up one level.
    
    i.e. get rid of the non-host terms so the proposed tree goes from this:
    
    [i]interaction with other organism
    ---[i]interaction with non-host organism
    ---[i]interaction with host organism
    
    to this:
    
    [i]physiological interaction with other organism
    ---[i]interaction between host and other organism

The word 'physiological' excludes interactions such as one animal hunting and
eating another animal. (Michelle and Candace agreed after the content meeting to change
the higher order term in the revised PAMGO proposal to "interaction between
host and other organism".) Any gene products that needed the 'non-host' concept
will be annotated to the parent term.
        
Action 6. Change 'competition with non-host' to 'competition with other'. N.B Michelle
and Alex exchanged email after the meeting and settled on the phrase "another, non-host,
organism" to describe better what "non-host" means. PAMGO agree with this. See
https://sourceforge.net/tracker/?func=detail&aid=1012931&group_id=36855&atid=440764
    
If you have 'interaction with host' terms, you may also need 'interaction with hostee'
terms. We need to incorporate this concept as needed. Idea: Taxon
field can take one or more entries.  Usually you are annotating from the perspective of
one organism.  But you can annotate from the perspective of more than one. For example,
Plasmodium takes gene products from other organisms and converts them to its own use.

Action 7. Suparna will look into adding 'host-side' processes or using taxonID to clarify
reciprocal terms as needed.

Action 8.  Change definition of 'cell-cell signaling' to mean between cells in the same
species.

Action 9.  Add 'within the same species' qualifier to the definition of 'pollen-pistil
interaction'

Action 10.  Consider adding 'within the same species' to the definition of terms for all
children of 'cell communication'.

    
--------------------------------------------------------------------------------    
    
Pathogenesis
============

Having discussed the term 'host-pathogen interaction' with reference to symbiosis, we
also discussed the use of the word 'pathogen'.

Background: The distinction of 'pathogenic' processes from 'normal' processes is quite
ambiguous; from the point of view of the infecting organism, all processes are quite
normal and yet we designate them pathogenic.

The PAMGO representatives suggested that the results for the host are something
different from health. On the host side, there are natural processes that occur
in an attempt by the host to prevent the pathogenic state from developing.
Therefore "pathogenesis" is a natural process and terms relating to it are
appropriate for GO. (N.B. symptoms do not belong in GO, although the underlying
responses that happen to give rise to symptoms may be valid GO processes.
A 'candidate' for a response term would have to be evaluated individually
by curators. Gene products involved in such host responses should not be
annotated to 'pathogenesis'.) In addition, many of the processes involved
in establishing a symbiotic interaction and establishing a pathogenic interaction are
identical, so we needed to create common terms.

Current structure (Michelle Gwinn):
Pathogenesis is currently under 'physiological process', and 'host-parasite interaction'
is in a different node, under 'cell process'. The virus terms are throughout both
ontologies, again in their own nodes.

B. Outline of problem (Jane Lomax): There are lots of potential true path violations e.g.
viruses are not cells, but virus-specific terms are ancestors of cellular processes.
This will become more of a problem as more pathogen groups join and want terms e.g.
the plant microbe group. It also means these groups will have some strange GO slims.
We need a systematic way of adding new terms that are specific to pathogens in a
similar way to the term 'host'.

The biological use of the word 'pathogenesis' was discussed. At least to some of the
plant people present, there is a clear difference between the concept of pathogenesis
as it is defined in plant and in mammal research fields. In mammals there are many
bacterial strains that live in the gut, and these may cause disease in some individuals
but not in others. This means that these bacterial strains are sometimes pathogenic
and sometimes not. However, some of the plant biologists present stated that in plant
biology a pathogen is considered to be a species that will always cause disease in
its target species, and that is adapted to fit this niche. They said that plant
pathogens are identified by their ability to inject virulence factors into the cells
of the target species as one of the first steps in the infection process. By this
view of things there would be a considerable difference in the way that the plant
research community and the mammal research community view pathogenesis. As a caveat
however, to this apparently clear distinction in viewpoint, it was noted that the
plant experts present were divided on the subject. Some of those present stated that
this view of plant pathogenesis is not a concept that all plant pathologists would
agree with.

To clarify the point, further information has been contributed after the meeting by
the PAMGO group:

"There are incredibly diverse ways in which various microbes interact with plants.
It is true that many of the best studied pathogens are dedicated pathogens whose
virulence depends on injecting virulence proteins into plant cells (the bacterium
Pseudomonas syringae is a good example). However, there are some very devastating
pathogens that appear to rely on diffusible low-MW toxins to defeat plant defenses
(the fungus Cochliobolus victoriae is a good example). There are also some P. syringae
strains that are able to inject 'virulence' proteins into plant cells, but they do
not cause disease on any plants tested. To further confuse things, the protein injection
system used by gram-negative bacterial pathogens (the type III secretion system)
shows up in some plant-associated bacteria that are mutualistic symbionts or commensals.
Also, the 'disease triangle' is a very real factor in many plant diseases, such that
environmental conditions can determine whether the interaction results in a symptomless
latent infection or active pathogenesis leading to symptoms. To summarize, even a
bacterium that is specialized to be able to inject virulence factors into plants
does not always do that - sometimes it just sits on the surface of leaves without
becoming a pathogen.  As we learn more about plant pathogens, it is likely that the
truth will be very much as expressed by Alex re: mammalian pathogens."

Action 11. PAMGO would feel comfortable defining pathogenesis in line with the mammal
model as explained by Alex and wish this to be considered in the continuing discussion
of this topic.

A proposal was made that in the term 'defense response to pathogenic bacteria', and
related terms, we should remove the word 'pathogenic', since 'defense response' by
itself implies that the thing is pathogenic so the two words are redundant. A further
proposal was made to replace the existing terms 'pathogenesis' and 'host-pathogen
interaction': Candace Collmer's suggestion is to create a tree where we don't specify
whether an interaction between two organisms is pathogenic or not, with top term
'interaction with other organism', to be a replacement for the existing terms pathogenesis
and host-pathogen interaction. (This term, 'interaction with other organism' has been
modified since the content meeting to be "interaction between organisms" in the PAMGO
revised)

Action 12.  Consider removing 'pathogenic' from defense terms as proposed and clarifying
definitions. This would also mean include 'response to pathogen' as synonym and still
keeping defense response of bacteria, fungi, etc. Terms would be normalized to 'defense
response to x' rather than 'pathogenic response to x'. There was a general majority
agreement that this should be implemented.

Action 13. The new term "interaction with other organism" should be a child of the parent
term "physiological process" and the definition of this new term ("interaction with
other organism") should be "the physiological process by which different organisms act
on, affect, or influence each other."    [Michelle Gwinn and Candace have agreed,
since the content meeting, that they will propose, in the modified PAMGO proposal,
to alter this term to "interaction between organisms", so that it will be ready to
later include terms related to the host side of the interaction (as was discussed at
the content meeting)].

Alex proposed replacing 'defense to pathogenic bacteria' with
'response to foreign biotic stimulus' i.e., foreign detected things.

Action 14.  Update definitions to include a definition of 'biotic' i.e. includes parts
derived from living organisms if not living organism itself.

The use of the word 'response' was discussed. We had difficulty defining the borderline
between the defense response and the immune response. For example, is the skin a defense
response? It is certainly a defense. Likewise is the presence of antibodies a 'defense
response' acted out over the evolutionary timescale? The example was given of the
'castle wall vs. the archers on castle wall'. The existence of the castle wall is
not a spur-of-the-moment response in the same way that sending archers on to the
castle wall is, but rather a pre-existing defense. However, you wouldn't build a
wall in the first place if you had not already perceived the need for defense. Do
we annotate castle wall situations as 'defense response'? Putting 'archers on the
castle wall' is certainly a defense response.

 
Action 15.     Clarify use of 'Response to' (define carefully)
    
    e.g. Can a response be pre-emptive or does it happen after the event?
    Are antibodies part of the response evolutionarily?
 
 
Evasion
=======

With reference to 'defense response' we also discussed evasion. A nematode living
in the lymph node to avoid the immune response could be considered to be using evasion
as a tactic. Do we need separate evasion and suppression terms, and a parent to use
for annotation if neither child is obviously appropriate?

Action 16.

original PAMGO proposal suggests:
       [i] interaction with host organism       
          ---[i] evasion or suppression of host defenses
       ------[i] evasion of host defense response GO:0030682

changed to:           
            
        [i] interaction between host and other organism
        ---[i] avoidance of host defenses
        ---------[i]evasion of host defenses
        -----------------[i] evasion of host defense response GO:0030682
        ---------[i]suppression of host defenses
        -----------------[i] suppression of host defense response GO:new

[N.B. It was also agreed in the meeting that 'evasion of host defenses' and
'suppression of host defenses' should be exact synonyms of 'avoidance of host
defenses' but Midori pointed out after the meeting that this would be redundant
with the child terms. Michelle, Candace and Alan have agreed to implement only the
child terms and not the synonyms.]
           
        
Action 17. Alex was to provide a new proposal based on discussion of 'defense' response
and see what PAMGO think. Since the meeting this has become a further discussion
item rather than an action item. He closed SF 1013068 on 9/20/2004 and submitted
a new proposal, Response and Detection Terms
(http://sourceforge.net/tracker/?func=detail&aid=1031159&group_id=36855&atid=440764).
To see the post-meeting developments please read this item.

General concern was expressed that synonyms cannot be accessed with many tools.

Action 18. Check for all tools that synonyms can be queried and displayed easily.

Summary
-------

The general consensus for the pathogenesis and symbiosis section was that the PAMGO
proposal was very good, and would be implemented pending some modifications (as outlined
above). Candace to submit an ammended version of the proposal to SF for further comment.

--------------------------------------------------------------------------------


The cell killing proposal
======================

See also the appendices:    
Background Reading From Jane On All Three Topics    
Alex Diehl's Pre-Meeting Proposal On Cell Killing Terms    
Alex's Cell Killing Proposal And Terms    
Cell Killing Terms Incorporating The Discussion At The Go Content Meeting    
    
This was a general discussion of cell killing, following on from Alex's proposal.    
    
Michelle Gwinn asked where bacterial autolysis would fit in with the proposed
cytolysis terms, as the definition of 'cell killing, self' excludes this process.
Autolysis is a normal process for bacteria under conditions of environmental stress,
and may serve to e.g. disseminate its DNA so it gets taken up by other cells.

Action 19. It was decided to add a new term (possibly microbial autolysis) directly under
cell death.

There is a difficulty in distinguishing between necrosis and apoptosis. David pointed
out that apoptosis involves destruction of plasma membrane earlier by the cell itself,
and Michelle confirmed this saying that necrosis was from outside while apoptosis was
internally controlled. Alex pointed out that a virus may cause apoptosis and that a
host may kill itself. He said he felt we needed to do more reading of reviews to see
how people are using the terms. Plant folks stated that the distinctions in plant
biology were quite murky but that it would be useful to have general term of 'cell
killing' at the moment. David mentioned that some biologists use the term 'apoptosis'
it to talk about the death of tissues but other groups use it as self-cell death.  
If necrosis is looked at it from a tissue level, necrotic cell death is looking at
it from a self-referential level. David further elaborated, explaining that necrosis
was originally defined pathologically, by watching the cell break up.  Late stage
apoptosis = necrosis.

Further points made by Alex:

- Cytolysis can mean self-killing or non-self-killing.
- Cytotoxicity is not the same as cytolysis.
- We could have a 'cell-mediated cell death during development' term.
    
Action 20. Autolysis should be an is-a child of cytolysis. Cytolysis remains a child of
cell death rather than becoming a child of cell killing, although some of its child
terms will have multiple parentage.

    cell death
       [i]programmed cell death
       [i]cytolysis
       ---[i]autolysis
       [i]cell killing
        
    
Action 21.  Change definition of cell killing to explicitly state the induction of cell
death in another cell. It was decided that the definition of 'cell killing' should
include some of the information currently assigned to the comment.

Action 22.  Remove 'cell killing, self', move up 'immune cell mediated cytotoxicity', make
consistency changes.

There was some discussion as to whether 'cell killing, self' and 'cell killing,
non-self' were split too low (see tree in handout).

Action 23. It was decided that many of the processes involved were common to both self
and non-self, so the level of the split suggested by Alex was okay.

Action 24. 'cell invasion' is to be moved. We did not decide where to.

Finally: To incorporate all of these changes into a single plan and to prepare them
for consideration at the consortium meeting:

Action 25. Alex will update the existing 'cell killing' SF entry
(https://sourceforge.net/tracker/?func=detail&aid=1012931&group_id=36855&atid=440764)
(Done on 17/9/2004.)
    
    
--------------------------------------------------------------------------------
To reiterate, following on from the three discussions above there are three
SourceForge Proposals: the PAMGO proposal (965023), "Response and Detection
Terms" (1031159), and "Cell Killing Proposal" (1012931). The further conclusions in
these items will be considered at the Consortium Meeting at Chicago in October.
    
--------------------------------------------------------------------------------


Metabolism:
===========

See also the appendices:
Background Reading From Jane On All Three Topics    
Metabolism Explanation Power-point Presentation.    
Metabolism Proposal Power-point Presentation.    


Current Structure - Midori

[i]physiological process
---[i]metabolism
[i]behavior
[i]cellular process
[i]development
[i]regulation of biological process
[i]viral life cycle


The big question is: What is the scope of the 'metabolism' concept? Metabolism can
be thought of as physiology at the biochemical level (or indeed the physiology of
biochemicals), so does fit under 'physiological process'.

At present, many children of 'metabolism' do not have 'cellular process' parentage
but biologists would expect to find them under cellular process.

Problems:
- We need to define where metabolism (of a particular substance, or generally) begins
  and ends.
- For unicellular organisms there is essentially a complete overlap between cellular
  and physiological processes.
- Is 'cellular physiological processes' the same as 'cell growth and maintenance'?
- Right now, metabolism includes a subset of physical changes but not transport activity
  and it should include anabolic and catabolic process.

David gave a presentation using glucose metabolism as an example. Much of glucose
metabolism, such as glycolysis and gluconeogenesis, occurs within the cell, but in
multicellular organisms, glucose homeostasis is systemic. We need to decide if the
regulation of blood glucose levels by insulin and glucagon count as components of
glucose metabolism, and what is the relationship between glucose homeostasis and
glucose metabolism?

(More details in appendix: Metabolism explanation power-point presentation.
ftp://ftp.geneontology.org/pub/go/meeting/minutes/20040822_Stanford_Content/
metabolism_explanation.pdf and
ftp://ftp.geneontology.org/pub/go/meeting/minutes/20040822_Stanford_Content/
metabolism_explanation.ppt)

We considered some of the defining features of metabolism concepts. Most, but not
all, metabolism involves production or consumption of energy. Metabolic processes
are not necessarily essential for cell growth or maintenance (consider secondary
metabolism). The current MetaCyc definition has 'all chemical reactions and
interactions in a biological system', but even Peter Karp thinks it's not wholly
satisfactory. Should we include or exclude things like protein phosphorylation,
and is post-translational modification a kind of protein metabolism? What about
metabolic pathways that require transport?

Action 26. We agreed to include such instances of
transport, but not transport generally, under metabolism. Reactome considers where
a process can be localized (including whether it's within a single cell or not).

We considered the relationship between metabolism and physiology. Some examples
of non-metabolic physiological processes include neurophysiology and transport.

However, transport has same issue as metabolism, e.g. transport within vs. between
cells, also long-range intracellular transport in multicellular organisms.

The same question extends to other physical changes. At present the definition of
'metabolism' in GO (which came from the Oxford Dictionary of Biochemistry and
Molecular Biology) includes physical changes, but Michael recommended, and the
group agreed, to restrict metabolism to chemical changes. (Michael spoke of
'transformation of substances', but we will use the wording 'chemical changes'
to avoid ambiguity -- e.g. a substance moving from outside the cell to inside
could be said to be 'transformed'.)

This change will mean that fewer supracellular processes will count as metabolism,
but will not remove all of them from consideration.

Sue proposed that the criterion for 'organismal' process should be that they require
more than one cell type.


We discussed these things and agreed on some new definitions and a new structure.

    Action 27. This is the agreed structure:
    
    physiological process
    [i]metabolism (GO:0008152)
    ---[i]organismal metabolism (new)
    ---[i]cellular metabolism (new)
    ---[i]primary metabolism (new)
    ---[i]secondary metabolism (GO:0019748)
    ---[i]anabolism (GO:0009058)
    ---[i]catabolism (GO:0009056)
    ---[i]regulation of metabolism
    ---[i]generation of precursor metabolites and energy (rename energy pathways,
    needs definition, consult MetaCyc def)
    
    This is the agreed cellular metabolism parentage:
    
    [i]Physiological process
    ---[i]Cellular physiological process
    ------[i]Cellular metabolism
    ---[i]Metabolism (GO:0008152)
    ------[i]Cellular metabolism
    [i]Cellular process
    ---[i]Cellular physiological process
    ------[i]Cellular metabolism
    
    Action 28. 'cellular physiological process' is to merge with 'cell growth and maintenance'.
        
    Action 29. This is the agreed 'organismal metabolism' parentage:
    
    [i]Physiological process
    ---[i]organismal physiological process
    ------[i]organismal metabolism
    ---[i]Metabolism (GO:0008152)
    ------[i]organismal metabolism


The new definitions proposed are detailed below:
    
Action 30. The definition of 'metabolism' was discussed, and will be altered.
At a minimum, references to physical changes will be deleted. If no further
changes are made, the definition would be:

'The chemical reactions that occur in living organisms, comprising anabolism and
catabolism; may be qualified to mean the chemical reactions undergone by a
particular substance, or class of substances, in a living organism.' [ISBN:0198547684]

A more extensive rewording also came about, and generally found favor:

Processes that cause many of the chemical changes in living organisms, including
anabolism and catabolism. Metabolic processes typically transform small molecules,
but also include macromolecular processes such as DNA repair and replication, and
protein synthesis and degradation. [comment or to be revisited: Metabolic processes
do not include single functions (or processes?) such as protein-protein interactions,
protein-nucleic acids, nor recepter-ligand interactions.]

Action item 31: Change the definition of 'metabolism'. The group prefers the second
option; if it is used, we must discuss whether to include a statement (as a comment)
about what processes are NOT considered metabolism, and, if so, how it should be worded.
    
Action 32. Secondary metabolism:
    
The current definition is:
    
Chemical reactions and physical changes that generate diverse byproducts that are
often unique to a taxon, are generally not essential for survival, and have no known
metabolic role. In multicellular organisms secondary metabolism is generally carried
out in specific cell types, and may be useful for the organism as a whole. In
unicellular organisms, secondary metabolism is often used for the production of
antibiotics or for the utilization and acquisition of unusual nutrients.' [GO:curators]

Action 33: Consider changing the definition; make sure everyone involved in the discussion
on the existing definition sees the proposal and approves. Also check the old SF item
    (https://sourceforge.net/tracker/?func=detail&atid=440764&aid=896576&group_id=36855).
    
There are two proposals for the new def. The first is a slight rewording of the current
one:

def 1:  Processes that result in many of the chemical changes of compounds that are not
required for growth and maintenance of cells, and are often unique to a taxon.
In multicellular organisms secondary metabolism is generally carried out in specific
cell types, and may be useful for the organism as a whole. In unicellular organisms,
secondary metabolism is often used for the production of antibiotics or for the
utilization and acquisition of unusual nutrients.

The second is the MetaCyc definition:

def 2:  Metabolism of secondary compounds, defined simply as compounds other than
primary compounds. A compound is classified as a secondary metabolite if it does not
seem to directly function in the processes of growth and development. Even though
secondary compounds are a normal part of the metabolism of an organism, they are often
produced in specialized cells, and tend to be more complex than primary compounds.
Examples of secondary compounds include antibiotics and plant chemical defenses such
as alkaloids and steroids.

Also in this def: change 'byproducts' to 'products'

Action 34. These further definitions were agreed:

Organismal metabolism: Metabolic processes in multicellular organisms that occur at
the tissue, organ, or organismal level. These processes, unlike cellular metabolism,
can include transport of substances between cells when that transport is required.

Cellular metabolism: Metabolic processes by which individual cells transform chemical
substances.

Primary metabolism: Primary metabolism encompasses reactions involving those compounds
which are formed as a part of the normal anabolic and catabolic processes. These
processes take place in most, if not all, cells of the organism.
MetaCyc (www.metacyc.org): Taiz, Lincoln, and Eduardo Zeiger. 'Surface Protection
and Secondary Defense Compounds.' Plant Physiology. New York: Benjamin/Cummings
Publishing Company, Inc., 1991: 320-345.

The question was asked: 'Where should the following terms go?'

- Energy pathways: Not defined.

Action 35. Reword to 'generation of precursor metabolites and energy'; add def based
on MetaCyc; put directly under metabolism.

- Electron transport: The transport of electrons from an electron donor to an
electron acceptor.
- Oxidative phosphorylation: The phosphorylation of ADP to ATP that accompanies
the oxidation of a metabolite through the operation of the respiratory chain.
Oxidation of compounds establishes a proton gradient across the membrane, providing
the energy for ATP synthesis.

Action 36: Put these two under the reworded energy pathways term.

- Metabolism resulting in cell growth: The chemical reactions and physical changes
that occur in living organisms that result in an increase in the mass (size) of a cell.

Action 37: Delete this term.
        
- long-term maintenance of gene activation: Any mechanism, at the level of
transcription or post-transcription, maintaining gene activation in the long-term.

Action 38: move this term to correct parent(s).

Action 39. Check through the metabolism terms and decide which are organismal and
which are cellular.

    Examples of organismal metabolism:
        C4 photosynthesis
        Salivary polysaccharide metabolism
        Lignification
        Starch metabolism
        organismal lipid metabolism
        Hibernation
    
We discussed the possibility of continuing to improve this node and to arrange
all the terms in their correct places in the new structure.

Action 40. Expand Metabolism Interest Group to include MetaCyc and Reactome folks.

Action 41. General Action Item:  Work on new approaches to supporting Interest Groups.  

(Current support for interest groups: Current support is restricted to listing the
members and their contact details on the GO website. A plan was formed that the
groups should communicate via the GO mailing list with the subject lines beginning
with the name of their interest group and a hyphen e.g. subject: 'development
- gametophyte development'. However, this generated a great deal of traffic on the
list an caused frustration for the many peripheral GO users who are subscribed.
Consequently this plan was abandoned and so the discussions of interest groups are
currently either on sourceforge or off-list. Off-list discussion are not archived
and so it is hoped that the conclusions of these discussions should be sent to the
list or added to sourceforge items. However, it is not clear that this occurs, or
that it would be sufficient even if it did.)
    
Action 42. Archived mailing lists will be created for the the interest groups:
    1. cell cycle,
    2. metabolism,
    3. pathogenesis/cell killing/immunology
    4. development
    
We discussed the regulation terms and the possible implementation of the 'regulates'
relationship.    
    
Action 43. Suzi to talk to Chris about a presentation on this (again). Presentation is
to make a specific proposal and outline methods/processes for implementation. Also
to present what the current problems are.

Action 44. We'd like to implement the new relationship type 'regulates' if this is agreed
to at the October meeting.

e.g. 'regulation of metabolism' regulates 'metabolism'.

If 'regulates' was represented by '*' then this DAG would look like this:
    
        -%metabolism
        --*regulation of metabolism.
    
(the star wasn't agreed in the meeting, I just did that in my notes. Ed.)
    
--------------------------------------------------------------------------------
    
Cell cycle
=========

See also the appendices:
Background Reading From Jane On All Three Topics    
Cell Cycle Power-point Presentation.    

Amelia: presentation on Cell Cycle  


    Summary of the current situation from Amelia's power-point presentation:
    
    [p]cytokinesis
    [p]cell cycle (under cell proliferation)
    ---[p]M phase
    ------[p]nuclear division
    ---------[i]meiosis
    ---------[i]mitosis
    ---[i]mitotic cell cycle
    ------[p]phases of the mitotic cell cycle - G1, G2, S
    ------[p]M phase of mitotic cell cycle
    ---------[p]cytokinesis after mitosis
    ---------[p]mitosis
    ------------[p]phases of mitosis: anaphase, metaphase, etc.
    ---------------[p]events occurring during each phase
    

Problems:
1) Current structure is based on yeast paradigm, which results in true path problems
for any species without paradigmatic mitosis and meiosis cycles.
2) Anything in 'resting' phase occurs under cell proliferation. Solution: split out
new high-level term of 'cell cycle phase'.
3) Timed events were under phases but this didn't work. solution: add terms such as
meiotic cell cycle phase progression.
    
Action 45. Split out the temporal elements of the cell cycle and have them stand alone
    
Action 46. Create the physical processes related to the cell cycle but do not relate
them to temporal components.
    
Action 47. Do not obsolete 'cytokinesis'
    
Action 48. Add the words 'phase progression' to the end of the 'high level' phase terms.
    
Action 49. 'x during cell cycle' terms are to be added.
    
Action 50. Look out for GO generic slim terms when making adjustments.
    
Action 51. Finish redefinition of 'cell cycle' in SourceForge.
    
Action 52. Find a good location for 'nuclear division'.

Action 53. The final proposal:
    
The proposal that came from the meeting can be downloaded at the sourceforge item page:
http://sourceforge.net/tracker/index.php?func=detail&aid=1025157&group_id=36855&atid=440764.
A few further improvements have been made since the meeting. Details are provided on that
page.
    
--------------------------------------------------------------------------------
    
Component ontology:
===================

There was a bit of spare time in the meeting during which a short presentation was
made by Peifen Zhang about work she has done on considering potential improvements
to the component ontology.

Action 54.
        1)  MetaCyc will make sourceforge requests for CC terms.
        2)  Will form Interest Group on revision of cellular component.
        3)  Will plan to have Content Meeting on CC to include MetaCyc and
        Reactome groups and Chris Mungall at least.
    

--------------------------------------------------------------------------------
APPENDICES

The remainder of this document contains the appendices. These are are the list of
action items, and the text files that were given as handouts at the meeting.

List of appendices:

1. Action items
2. Agenda.
3. Background reading from Jane on all three topics.
4. The pre-meeting PAMGO obo file.
5. Alex Diehl's pre-meeting proposal on pathogenic terms (sourceforge url).
6. Alex Diehl's pre-meeting proposal on Cell Killing terms (sourceforge url).
7. Comments from Matt Berriman on the pathogenesis proposals.
8. Pathogenesis powerpoint presentation.
9. PAMGO powerpoint presentation.
10. Metabolism explanation powerpoint presentation.
11. Metabolism proposal powerpoint presentation.
12. Cell Cycle powerpoint presentation.
13. Alex's proposal: Pathogenic Terms I want to change or eliminate from the GO.
14. Alex's Cell Killing Proposal and Terms
15. Alex's Cell Killing Terms incorporating the discussion at the GO Content meeting
16. Suparna's proposal on host-pathogen interactions. (url)


---------------------------------------------------------------
Action items.


Action 1. Establish common parents and replicate subtrees for symbionts and pathogens as
appropriate, e.g.
      
            [i]acquisition of nutrients from host
            ---[i]acquisition of nutrients from host during symbiosis
            ---[i]acquisition of  nutrients from host during pathogenesis

Action 2. Should PAMGO define symbiosis to exclude parasitism or pathogenesis in their
modified proposal? This remains a point for further discussion.

Action 3. Define host based on PAMGO definition (To be taken from:
% interaction with host organism
Def: any interaction between an organism, usually a parasite or symbiont, and another
organism from which it may obtain nourishment, protection, and/or a means of dispersal.

Action 4. We need a name and a definition for the 'hostee'; the dependent organism in a
relationship, e.g. a parasite.    
    
Action 5. Remove 'interaction with non-host organism' and move sub-terms up one level.
    
    i.e. get rid of the non-host terms so the proposed tree goes from this:
    
    [i]interaction with other organism
    ---[i]interaction with non-host organism
    ---[i]interaction with host organism
    
    to this:
    
    [i]physiological interaction with other organism
    ---[i]interaction between host and other organism

Action 6. Change 'competition with non-host' to 'competition with other'. N.B Michelle
and Alex exchanged email after the meeting and settled on the phrase "another, non-host,
organism" to describe better what "non-host" means. PAMGO agree with this. See
https://sourceforge.net/tracker/?func=detail&aid=1012931&group_id=36855&atid=440764
    
Action 7. Suparna will look into adding 'host-side' processes or using taxonID to clarify
reciprocal terms as needed.

Action 8.  Change definition of 'cell-cell signaling' to mean between cells in the same
species.

Action 9.  Add 'within the same species' qualifier to the definition of 'pollen-pistil
interaction'

Action 10.  Consider adding 'within the same species' to the definition of terms for all
children of 'cell communication'.

Action 11. PAMGO would feel comfortable defining pathogenesis in line with the mammal
model as explained by Alex and wish this to be considered in the continuing discussion
of this topic.

Action 12.  Consider removing 'pathogenic' from defense terms as proposed and clarifying
definitions. This would also mean include 'response to pathogen' as synonym and still
keeping defense response of bacteria, fungi, etc. Terms would be normalized to 'defense
response to x' rather than 'pathogenic response to x'. There was a general majority
agreement that this should be implemented.

Action 13. The new term "interaction with other organism" should be a child of the parent
term "physiological process" and the definition of this new term ("interaction with
other organism") should be "the physiological process by which different organisms act
on, affect, or influence each other."    [Michelle Gwinn and Candace have agreed,
since the content meeting, that they will propose, in the modified PAMGO proposal,
to alter this term to "interaction between organisms", so that it will be ready to
later include terms related to the host side of the interaction (as was discussed at
the content meeting)].

Action 14.  Update definitions to include a definition of 'biotic' i.e. includes parts
derived from living organisms if not living organism itself.
 
Action 15.     Clarify use of 'Response to' (define carefully)
    
    e.g. Can a response be pre-emptive or does it happen after the event?
    Are antibodies part of the response evolutionarily?
 
Action 16.

original PAMGO proposal suggests:
       [i] interaction with host organism       
          ---[i] evasion or suppression of host defenses
       ------[i] evasion of host defense response GO:0030682

changed to:           
            
        [i] interaction between host and other organism
        ---[i] avoidance of host defenses
        ---------[i]evasion of host defenses
        -----------------[i] evasion of host defense response GO:0030682
        ---------[i]suppression of host defenses
        -----------------[i] suppression of host defense response GO:new

Action 17. Alex was to provide a new proposal based on discussion of 'defense' response
and see what PAMGO think. Since the meeting this has become a further discussion
item rather than an action item. He closed SF 1013068 on 9/20/2004 and submitted
a new proposal, Response and Detection Terms
(http://sourceforge.net/tracker/?func=detail&aid=1031159&group_id=36855&atid=440764).
To see the post-meeting developments please read this item.

Action 18. Check for all tools that synonyms can be queried and displayed easily.

Action 19. It was decided to add a new term (possibly microbial autolysis) directly under
cell death.

Action 20. Autolysis should be an is-a child of cytolysis. Cytolysis remains a child of
cell death rather than becoming a child of cell killing, although some of its child
terms will have multiple parentage.

    cell death
       [i]programmed cell death
       [i]cytolysis
       ---[i]autolysis
       [i]cell killing
        
    
Action 21.  Change definition of cell killing to explicitly state the induction of cell
death in another cell. It was decided that the definition of 'cell killing' should
include some of the information currently assigned to the comment.

Action 22.  Remove 'cell killing, self', move up 'immune cell mediated cytotoxicity', make
consistency changes.

Action 23. It was decided that many of the processes involved were common to both self
and non-self, so the level of the split suggested by Alex was okay.

Action 24. 'cell invasion' is to be moved. We did not decide where to.

Action 25. Alex will update the existing 'cell killing' SF entry
(https://sourceforge.net/tracker/?func=detail&aid=1012931&group_id=36855&atid=440764)
(Done on 17/9/2004.)
        
--------------------------------------------------------------------------------
To reiterate, following on from the three discussions above there are three
SourceForge Proposals: the PAMGO proposal (965023), "Response and Detection
Terms" (1031159), and "Cell Killing Proposal" (1012931). The further conclusions in
these items will be considered at the Consortium Meeting at Chicago in October.
    
Action 26. Metabolic pathways that require transport:
 We agreed to include such instances of
transport, but not transport generally, under metabolism. Reactome considers where
a process can be localized (including whether it's within a single cell or not).

Action 35. Reword to 'generation of precursor metabolites and energy'; add def based
on MetaCyc; put directly under metabolism.

- Electron transport: The transport of electrons from an electron donor to an
electron acceptor.
- Oxidative phosphorylation: The phosphorylation of ADP to ATP that accompanies
the oxidation of a metabolite through the operation of the respiratory chain.
Oxidation of compounds establishes a proton gradient across the membrane, providing
the energy for ATP synthesis.

Action 36: Put these two under the reworded energy pathways term.

- Metabolism resulting in cell growth: The chemical reactions and physical changes
that occur in living organisms that result in an increase in the mass (size) of a cell.

Action 37: Delete this term.
        
- long-term maintenance of gene activation: Any mechanism, at the level of
transcription or post-transcription, maintaining gene activation in the long-term.

Action 38: move this term to correct parent(s).

Action 39. Check through the metabolism terms and decide which are organismal and
which are cellular.

Action 40. Expand Metabolism Interest Group to include MetaCyc and Reactome folks.

Action 41. General Action Item:  Work on new approaches to supporting Interest Groups.  

Action 42. Archived mailing lists will be created for the the interest groups:
    1. cell cycle,
    2. metabolism,
    3. pathogenesis/cell killing/immunology
    4. development
    
Action 43. Suzi to talk to Chris about a presentation on this (again). Presentation is
to make a specific proposal and outline methods/processes for implementation. Also
to present what the current problems are.

Action 44. We'd like to implement the new relationship type 'regulates' if this is agreed
to at the October meeting.

Action 45. Split out the temporal elements of the cell cycle and have them stand alone
    
Action 46. Create the physical processes related to the cell cycle but do not relate
them to temporal components.
    
Action 47. Do not obsolete 'cytokinesis'
    
Action 48. Add the words 'phase progression' to the end of the 'high level' phase terms.
    
Action 49. 'x during cell cycle' terms are to be added.
    
Action 50. Look out for GO generic slim terms when making adjustments.
    
Action 51. Finish redefinition of 'cell cycle' in SourceForge.
    
Action 52. Find a good location for 'nuclear division'.

Action 53. The final proposal:
    
The proposal that came from the meeting can be downloaded at the sourceforge item page:
http://sourceforge.net/tracker/index.php?func=detail&aid=1025157&group_id=36855&atid=440764.
A few further improvements have been made since the meeting. Details are provided on that
page.
    
Action 54.
        1)  MetaCyc will make sourceforge requests for CC terms.
        2)  Will form Interest Group on revision of cellular component.
        3)  Will plan to have Content Meeting on CC to include MetaCyc and
        Reactome groups and Chris Mungall at least.
    
End of action item list.

-------------------------------------------------------------------------
2. Agenda for content meeting
Seminar room, Carnegie Institution, Stanford, CA.

Sunday 22nd August

(Those staying at SLAC meet at 8.15am in the lobby to organise cars to Carnegie Institution).

8.30 - 9.00am continental breakfast
9.00 - 9.30am introductions/logistics
9.30am    pathogenesis/cell killing
        1. Current structure - Michelle
        2. Outline of problem - Jane
10.30 - 11am tea and coffee break
11am    pathogenesis/cell killing cont.
        3. Proposals - Candace (PAMGO) - see proposal in SF.
                     - Suprana
        4. Discussion
1pm - 2pm lunch
2pm    pathogenesis/cell killing cont.
        4. Discussion cont.
        5. Action items
3.30pm - 4pm tea and coffee break
4pm    metabolism
        1. Current structure - Midori
        2. Outline of problem - David
5.30pm end
7pm - dinner at local Gordon Biersch microbrew pub, where there will be 2 hrs of
all you can drink beer with a set menu (salad choices, main choices, dessert
choices).

Monday 23rd August
8.30 - 9.00am continental breakfast
9.00 - 9.30am logistics/introductions
9.30am    metabolism cont.
        3. Proposals:
            Jane
            Sue
        4. Discussion
10.30 - 11am tea and coffee break
11am    metabolism cont.
        4. Discussion cont.
        5. Action itmes
1pm - 2pm lunch
2pm    cell cycle
        1. Current structure - Amelia
        2. Outline of problem - Amelia
        3. Proposals - Amelia
        4. Discussion
3.30pm - 4pm tea/coffee break
4pm    cell cycle cont.
        5. Action items
4.30pm summary/future directions
5.30pm end
Dinner in San Fransisco if enough interest.


---------------------------------
3. Background reading from Jane on all three topics:


First GO Content Meeting
August 22-23, 2004
Carnegie Institution, Department of Plant Biology, Stanford, CA 94305
Organizers: Jane Lomax (jane@ebi.ac.uk), Sue Rhee (rhee@acoma.stanford.edu)


Purpose: To bring together GO group members and a few domain experts in person
to review and discuss three problematic areas in the GO process ontology,
metabolism, pathogenesis, and cell cycle, in order to come up with acceptable
solutions and specific action items to resolve the problems.

Agenda:

I. Pathogenesis summary

A. Current structure (Michelle Gwinn): pathogenesis is currently under
'physiological process', and 'host-parasite interaction' is in a different node,
under 'cell process'. The virus terms are throughout both ontologies, again in
their own nodes.

B. Outline of problem (Jane Lomax): Lots of potential true path violations e.g.
viruses are not cells, but virus-specific terms are ancestors of cellular
processes. Will become more of a problem as more pathogen groups join and want
terms e.g. the plant microbe group. It also means these groups will have some
strange GO slims. We need a systematic way of adding new terms that are specific
to pathogens in a similar way to the term 'host'.  See the email thread:

http://www.geneontology.org/email-go/go-arc/go-2004/0560.html

and the SF items:

cell killing:
https://sourceforge.net/tracker/index.php?func=detail&aid=900600&group_id=36855&atid=440764

viral parasite terms relationship to host:
https://sourceforge.net/tracker/index.php?func=detail&aid=895787&group_id=36855&atid=440764

The distinction of 'pathogenic' processes is quite artificial; from the point of
view of the infecting organism, all processes are quite normal and yet we
designate them pathogenic. In addition, many of the processes involved in
establishing a symbiotic interaction and establishing a pathogenic interaction
are very identical, so we need to create common terms (see PAMGO proposal
attached).

C. Proposals:
1. Candace Collmer (PAMGO) - create a tree where we don't specify whether an
interaction between two organisms is pathogenic or not, with top term
'interaction with other organism', to replace existing terms pathogenesis and
host-pathogen interaction. See SF item:

https://sourceforge.net/tracker/?group_id=36855&atid=440764&func=detail&aid=965023

and Appendix I.

2. Suparna Mundodi (TAIR) - integrating 'response to' terms into the proposed PAMGO tree.

3. Alex Diehl (MGI) - cell killing hierarchy proposal. See SF item:

http://sourceforge.net/tracker/?func=detail&aid=960898&group_id=36855&atid=440764

D. Additional questions:

- Can the 'response to parasite' etc terms be incorporated into this new structure?
- Pathogenic v/s non-pathogenic xxx responses. Are these still useful classifications?
- Are the proposed terms intuitive - will annotators understand them?
- What about component terms? We currently use 'host'.


II. Metabolism summary

A. Current Structure (Midori Harris): Metabolism is a child of 'physiological
process' only. Children of metabolism are grouped by type of metabolism
(catabolism or anabolism) and by substrate (e.g. lipid metabolism). Although
there is 'secondary metabolism' term, there is not 'primary metabolism' term.

The metabolism branch can be found at:
http://www.godatabase.org/cgi-bin/amigo/go.cgi?open_1=GO:0003673&open_1=GO:
0008150&open_1=GO:0007582

B. Original Problem (David Hill): Metabolism is a child of physiological processes, but
not cellular process.

SourceForge thread illustrating the initial communications about this issue:
https://sourceforge.net/tracker/index.php?func=detail&aid=814460&group_id=36855&atid=440764

Subsequent GO email communication about this issue:
http://www.geneontology.org/email-go/go-arc/go-2004/subject.html
(Go to 'metabolism split' section)

C. Proposals (not necessarily mutually exclusive)
1. Jane: split into cellular and organismal metabolism and put cellular
metabolism under cellular process.
2. Sue: put metabolism at a higher node at
the same level as physiological processes and put a bit more structure under it.

D. Additional Questions:
- Is metabolism really a child of physiological processes? What is the rationale
for either view?
- Does metabolism occur only at the cellular level? Are there
any examples of metabolism that occur at the supracellular (organismal/tissue)
level? Are there any examples of metabolism that occurs ONLY at the cellular
level?
- Do these questions also apply to transport processes?


III. Cell cycle summary

A. Original problem: cytokinesis is not part of the cell cycle but it seems as
if it should be. This then brought up other issues involving cell division /
replication events that occur in organisms which do not have a canonical cell
cycle.

Sourceforge thread illustrating the initial communications about this issue:

cytokinesis (0000910)/cell cycle relationship
https://sourceforge.net/tracker/index.php?func=detail&aid=815892&group_id=36855&atid=440764

A couple of other related SourceForge items on the cell cycle:

[ 931134 ] meiosis, mitosis and the cell cycle
http://sourceforge.net/tracker/?group_id=36855&atid=440764&func=detail&aid=931134

[ 822657 ] M phase of meiotic cell cycle
http://sourceforge.net/tracker/?group_id=36855&atid=440764&func=detail&aid=822657

GO email communication about this issue:
http://www.geneontology.org/email-go/go-arc/go-2004/1029.html and subsequent thread.

B. Current structure:
cell cycle and cytokinesis are siblings; all the events in the cell cycle are
underneath the cell cycle stages.

cell proliferation
[p]cytokinesis
[p]cell cycle
---[p]M phase
------[i]M phease of mitotic cell cycle
---------[p]mitosis
------[p]nuclear division
---------[i]meiosis
---------[i]mitosis
---[p]mitotic cell cycle
------[p]phases of the mitotic cell cycle - G1, G2, S
------[p]M phase of mitotic cell cycle
------[p]mitosis
---------[p]cytokinesis after mitosis
---------[p]phases of mitosis: anaphase, metaphase, etc.
------------[p]events occurring during each phase

C. Proposal:
1. Split cell cycle into cell cycles stages - eg. M phase, prophase, leptotene -
and cell cycle events - eg. meiosis, chromosome segregation, cytokinesis.

D. (Additional) Questions/Issues:
-Cell cycle events are currently all children of cell proliferation, the rapid
division and multiplication of cells. Do we need a term to encompass non-rapid
cell replication? I would suggest a generic parent of 'cell division' for cell
cycle and cell proliferation.

Appendix I - PAMGO suggested changes.

The bare tree of the proposed PAMGO terms (with some existing GO terms integrated):

biological process - physiological process (GO:0007582)
-%interaction with other organism
--%interaction with non-host organism
---%Competition with non-host organism
----%killing of non-host cells
---%biofilm formation (GO:0042710)
--%interaction with host organism
---%virus-host interaction (GO:0019048)
----%viral host cell process manipulation (GO:0019054)
----%viral host defense evasion (GO:0019049)
----%viral induction of host immune response (GO:0046730)
---%recognition of host
---%adhesion to host
----%cytoadherence to microvasculature (GO:0020035)
---%growth on or near host surface
---%entry into host
----%entry into host through natural portals
----%entry into host through host barriers
----%cell invasion (GO:0030260)
-----%viral entry (GO:0046718)
---%evasion or suppression of host defenses
----%evasion of host defense response (GO:0030682)
-----%evasion of host immune response (GO:0020012)
-----%viral host defense evasion (GO:0019049)
---%induction of host defense response
----%viral induction of host immune response (GO:0046730)
---%translocation of molecules into host
----%translocation of DNA into host
----%translocation of protein into host
-----%type III protein secretion system (GO:0030254)
---%movement within host
----%migration within host
----%viral spread within host (GO:0046739)
---%acquisition of nutrients from host
---%modification of host morphology or physiology
----%viral host cell process manipulation (GO:0019054)
----%viral transformation (GO:0019087)
-----%viral immortalization (GO:0019088)
----%disruption of host cells
-----%killing of host cells
------%hemolysis (GO:0019836)
------%necrosis (GO:0008220)
----%induction in host of a tumor, nodule, or growth
-----%induction in host of a tumor, nodule, or growth containing transformed cells
-----%induction in host of a tumor, nodule, or growth not containing transformed cells
---%dissemination or transmission of an organism from a host
----%dissemination or transmission of an organism from a host by a vector
----%viral transmission (GO:0019089)
-%cell killing
--%killing of non-host cells
--%killing of host cells


DRAFT -- New GO terms from PAMGO - from 4/23/04 PAMGO meeting, plus all changes
via email discussion among PAMGO members since then,  plus some integrations of
existing GO terms - as of end of day, 6/01/04


biological process - physiological process (GO:0007582)

---% interaction with other organism
------% interaction with non-host organism
---------% competition with non-host organism
------------% killing of non-host cells
---------% biofilm formation (GO:0042710
------% interaction with host organism -
---

 interaction with other organism
def: the processes by which organisms act on, affect, or influence each other
interaction with non-host organism
def: any process in which an organism interacts with another organism that does not
act as its host
competition with non-host organism
def: any process by which one community member  gains an advantage in growth or survival
over another community member
 killing of non-host cells
def: any process in an organism that results in the death of another, non-host organism
or its cells
 biofilm formation (GO:0042710
def: A process whereby microorganisms irreversibly attach to and grow on a surface and
produce extracellular polymers that facilitate attachment and matrix formation, resulting
in an alteration in the phenotype of the organisms with respect to growth rate and gene
transcription)
interaction with host organism
def: any interaction between an organism, usually a parasite or symbiont, and another
organism from which it may obtain nourishment, protection, and/or a means of dispersal




[NOTE: we suggest that this Physiological Process term replace both the Cellular
Process term "GO:0030383 = host-pathogen interaction", and the Physiological
Process term "GO:0009405 = pathogenesis"  in order to more easily group
processes related to pathogenesis (and symbiosis) that may be difficult to
cleanly define as either cellular or physiological.  We also hope to make this
new term more broad, thus incorporating interactions between host and pathogen
as well as between host and symbiont (as many of the processes involved are
shared by both, and sometimes the outcome [pathogenesis vs. symbiosis] can vary
depending on other conditions [e.g. environment, host defense response, etc.],
as previously discussed on the GO Consortium discussion list.  Thus, the outcome
should not be pre-judged.)  We feel this will better serve the needs of those
searching across organisms for gene products involved in this more
broadly-defined process of inter-organismic interactions. However, this now
brings us into the realm of a discussion on the GO Consortium email that took
place earlier this year - whether "pathogenesis" should include gene products
like the human protein huntingtin, which can cause disease in humans -
Huntington's disease - when it is mutated.  While I did not think that GO
currently annotates functions of proteins that are true only when they are
mutated, that particular gene product (huntingtin)  is  currently annotated
under the current GO term "pathogenesis."  If our suggested new term
"interaction with host organism" and its suggested children now serve as terms
to use in annotating disease-causing molecules in pathogens (and symbionts), GO
will need a new term and definition to accommodate the annotation of gene
products such as huntingtin.]


---------% virus-host interaction (GO:0019048
------------% viral host cell process manipulation (GO:0019054)
------------% viral host defense evasion (GO:0019049)
------------% viral induction of host immune response (GO:0046730)
---------% recognition of host
---------% adhesion to host
------------% cytoadherence to microvasculature (GO:0020035
---------% growth on or near host surface
---------% entry into host
------------% entry into host through natural portals
------------% entry into host through host barriers
------------% cell invasion (GO:0030260
---------------% viral entry (GO:0046718
---------% evasion or suppression of host defenses
------------% evasion of host defense response (GO:0030682
---------------% evasion of host immune response (GO:0020012)
---------------% viral host defense evasion (GO:0019049)
---------% induction of host defense response
------------%viral induction of host immune response (GO:0046730)
---------% translocation of molecules into host
------------% translocation of DNA into host
------------% translocation of protein into host
---------------% type III protein secretion system (GO:0030254
---------% movement within host
------------% migration within host
------------%viral spread within host (GO:0046739)
---------% acquisition of nutrients from host
---------% modification of host morphology or physiology
------------% viral host cell process manipulation (GO:0019054
------------% viral transformation (GO:0019087
---------------% viral immortalization (GO:0019088)
------------% disruption of host cells
---------------% killing of host cells
------------------% hemolysis (GO:0019836)
------------------% necrosis (GO:0008220  
------------% induction in host of a tumor, nodule, or growth
---------------% induction in host of a tumor, nodule, or growth containing transformed cells
---------------% induction in host of a tumor, nodule, or growth not containing transformed cells
---------% dissemination or transmission of an organism from a host
------------% dissemination or transmission of an organism from a host by a vector
------------% viral transmission --  (GO:0019089
---% cell killing
------% killing of non-host cells
------% killing of host cells


---
defs:


% virushost interaction (GO:0019048)
def:interactions, directly with the host cell macromolecular machinery, to allow virus
replication)

% recognition of host
def:the specific processes that allow an organism to detect the presence of a host via
physical or chemical signals

% adhesion to host
def:the attachment of an organism to its host via adhesion molecules, general stickiness,
etc., either directly or indirectly

% cytoadherence to microvasculature (GO:0020035)
def:adherence of parasiteinfected erythrocytes to microvascular endothelium.  
[NOTE: this GO term has been moved, unchanged, from its place as a child of
"hostpathogen interactions" to a child of newly proposed term "adhesion to host,"
which is itself a child of newly proposed term "interaction with host organism"]

% growth on or near host surface
def:an increase in size or number of an organism on or near the  exterior of its host.

% entry into host
def:penetration by an organism into the body, cells, or tissues of the host  
(Question: make "invasion into host" a synonym???)

% entry into host through natural portals -
def: penetration by an organism to the inside of a host via naturally occurring
openings in the host

% entry into host through host barriers
def: penetration by an organism to the inside of a host via active breaching of
physical barriers

% cell invasion (GO:0030260
def:invasion of a host cell by another cell (microorganism) or virus.)

% viral entry (GO:0046718
def:the process by which a virion enters a host cell, including virion attachment
and penetration.  [NOTE: We suggest that this term be made a child of "cell invasion"
in addition to its current place as a child of "initiation of viral infection")

(NOTE: We propose that currently existing GO term, GO:0001404
-Invasive growth (currently a child of "pathogenesis"), should be deleted. That
term is used differently for plant and animal pathogens, and there are currently
no gene products annotated to this term in GO.)

% evasion or suppression of host defenses
def: any process by which an organism  avoids, minimizes, or suppresses the effects
of a host defense(s), which can be either basal or induced

[NOTE: we suggest that this term become a broader parent term to "GO:0030682
-evasion of host defense response" [currently a child of "hostpathogen interaction"]
in order to define this process more broadly and to serve both pathogens and
symbionts, etc.  Also, we wanted to broaden the definition beyond a host "response,"
as some defenses are preformed rather than responsive. We think this will work in
all current trees. The term "GO:0030682
-evasion of host defense response" then becomes a child of this new term, and this
GO term's currently existing children terms "GO:0020012
-evasion of host immune response" and "GO:0019049
-viral host defense evasion", as well as their respective children terms, should be
able to stay at their current places in the tree under GO:0030682, as seen below.]

% evasion of host defense response (GO:0030682
def:any process by which a pathogen evades or minimizes the effects of a defense
response mounted against it by its host.

% induction of host defense response
def:the triggering by an organism of reactions in a host that can act to protect
the host cell(s) or host organism

% translocation of molecules into host
def:the directed movement of a molecule(s) produced by an organism to a location
inside the host

% type III protein secretion system (GO:0030254
def:a bacterial secretion system in which secretion occurs in a continuous process
without the distinct presence of periplasmic intermediates; does not involve
proteolytic processing of secreted proteins [Note: the definition of this term
needs correction in order to differentiate it from the other protein secretion
systems in bacteria.  We'll send in a request to do that very soon.]

% movement within host
def:the process by which an organism or its progeny spreads from one location
to another within a host

% migration within host
def:the directional movement of an organism from one place to another within a host

% acquisition of nutrients from host
def:the production of structures and/or molecules in an organism that are required
for the acquisition and/or utilization of nutrients obtained from its host

% modification of host morphology or physiology
def:the process of effecting a change in the structure or function of a host by
means of molecules produced by an associated organism

% viral host cell process manipulation (GO:0019054
def:alteration of defined cellular processes that viruses target during replication)

% viral transformation (GO:0019087
def:any virus-induced change in the morphological, biochemical, or growth parameters
of a cell)

% disruption of host cells
def:any process in an organism that results in damage to the structure or function of
the cell

% killing of host cells
def:any process in an organism that results in the death of its host or cells of its
host  

% hemolysis (GO:0019836)
def:"the processes that cause hemolysis, the lytic destruction of red blood cells with
the release of intracellular hemoglobin, in another organism."  [Note: This term is
currently a child of "pathogenesis"
- we suggest it be moved to here.]

% necrosis (GO:0008220
def:"the processes that cause necrosis, the death of tissues, in another organism".
[Question: What to do with this current GO term, currently a child of "pathogenesis"??
Should the 13 terms currently annotated here be transferred to "killing of host cell(s)"
and the "necrosis" term obsoleted?  "Necrosis" could be made a synonym of this term, or
they could be merged and "necrosis" become a secondary term under the new one ???]

% induction in host of a tumor, nodule, or growth
def:the process by which an associated organism causes the formation of an abnormal
mass of cells in the host

% induction in host of a tumor, nodule, or growth containing transformed cells
def:the process by which an associated organism causes the formation in a host of
an abnormal growth whose cells have been transformed and continue to exist in the
absence of the inducing organism. [NOTE: We suggest this should replace the current
GO term "host cell immortalization" (GO:0020021
- the modification of a host cell into an immortal cell line as a consequence of
infection), which currently has no genes annotated to it.]

% induction in host of a tumor, nodule, or growth not containing transformed cells
def:the process by which an associated organism causes the formation in a host of
an abnormal growth whose cell size or number has increased but which is not
sustained in the absence of the inducing organism

% dissemination or transmission of an organism from a host
def:the movement of an organism from a host to another host or another place in
the environment

% viral transmission --  (GO:0019089
def: the transfer of virions in order to create new infection)

% cell killing
def:any process in an organism that results in the death of another organism or
its cells

% killing of non-host cells
def:any process in an organism that results in the death of another, non-host
organism or its cells

% killing of host cells
def:any process in an organism that results in the death of its host or cells of its host

-------------------------------------

4. The pre-meeting PAMGO obo file can be downloaded from
[ 965023 ] new terms requested by PAMGO
https://sourceforge.net/tracker/?group_id=36855&atid=440764&func=detail&aid=965023
The file is just called 'pango'

------------------------------

5. Alex Diehl's pre-meeting proposal on pathogenic terms
[ 1013068 ] Pathogenic Terms
https://sourceforge.net/tracker/?group_id=36855&atid=440764&func=detail&aid=1013068

------------------------------

6. Alex Diehl's pre-meeting proposal on Cell Killing terms
[ 1012931 ] Cell Killing Proposal
https://sourceforge.net/tracker/?group_id=36855&atid=440764&func=detail&aid=1012931

-------------------------------


7. Comments from Matt Berriman on the pathogenesis proposals:

Some comments on the pathogenesis proposals by Matt Berriman.


biofilm formation
=================
appears as a child of interaction with non-host organism.  However, bio-film
formation plays a major role in the pathogenesis of many candida species.

the definition of biofilm formation mentions alteration in growth rate and gene
expression.  This seems to me to be unnecessarily restrictive.


interaction with host organism
==============================
I agree that host-pathogen interactions can be quite easily be changed to the
proposed interaction with host organism.

pathogenesis
============
the case of the huntingtin protein seems to me ato be a miss-annotation. What is
the normal role of that gene product in a human without huntington's?  If it is
not known, there are terms for that.

entry into host
===============
I don't think that this is synonymous with "invasion into host".  I use invasion
to describe a complex series of events leadiong to the penetration of host cells
by a pathogen.  This is very different to simply entering the body, rather than
individual cells, of a host.  A more suitable synonym for invasion into host
looks like cell invasion.

invasive growth
===============
what terms should be used to annotate invasive growth of Aspergillus into human
cells when it uses them as a nutrient source?

Viral terms
===========
it is not clear to me why distinctions need to be made for viral terms e.g...

Viral host defense evasion
=========================
why does the term need to include "viral"?  I presume the term means evasion of
host by a virus, not evasion of a viral host   However, still don't see why the
distinction between defence by viruses and by other pathogens needs to be made.

also,

viral immortailzation (which presumably should be written immortalisation by a virus)
=====================
is this different to immortalisation by a protozoan (e.g. Theileria). Answer is
that we don't know yet.

----------------------------------

8. Pathogenesis powerpoint presentation.

ftp://ftp.geneontology.org/pub/go/meeting/minutes/20040822_Stanford_Content/pathogenesis.pdf
ftp://ftp.geneontology.org/pub/go/meeting/minutes/20040822_Stanford_Content/pathogenesis.ppt

----------------------------------

9. PAMGO powerpoint presentation.

ftp://ftp.geneontology.org/pub/go/meeting/minutes/20040822_Stanford_Content/PAMGO.pdf
ftp://ftp.geneontology.org/pub/go/meeting/minutes/20040822_Stanford_Content/PAMGO.ppt

----------------------------------

10. Metabolism explanation powerpoint presentation.

ftp://ftp.geneontology.org/pub/go/meeting/minutes/20040822_Stanford_Content/
metabolism_explanation.pdf
ftp://ftp.geneontology.org/pub/go/meeting/minutes/20040822_Stanford_Content/
metabolism_explanation.ppt

----------------------------------

11. Metabolism proposal powerpoint presentation.

ftp://ftp.geneontology.org/pub/go/meeting/minutes/20040822_Stanford_Content/
metabolism_proposal.pdf
ftp://ftp.geneontology.org/pub/go/meeting/minutes/20040822_Stanford_Content/
metabolism_proposal.ppt

----------------------------------

12. Cell Cycle powerpoint presentation.

ftp://ftp.geneontology.org/pub/go/meeting/minutes/20040822_Stanford_Content/cell_cycle.pdf
ftp://ftp.geneontology.org/pub/go/meeting/minutes/20040822_Stanford_Content/cell_cycle.ppt

----------------------------------

13. Alex's proposal on Pathogenic Terms to change or eliminate from the GO

Basically, I want to eliminate all references to pathogens, pathogenic, or
pathogenesis from all GO terms and definitions.

The following is a excerpt of part of my email of 4 March 2004:

What we call "pathogenesis" is a human perspective to normal behavior by
microorganisms.  What we need in the GO is a class of terms that refer to
processes induced in a host organism by a microorganism or parasite.  Many of
these processes may well be benign for the host, some may be considered
pathogenic, but the GO terms used should be neutral on this point.

In fact, the PAMGO proposal accords well with this viewpoint.

In most cases below where no replacement term is offered, annotations can be
directly transferred to the parent terms.

There are some references to "pathogen" in some plant related terms (GO:0009689,
GO:0009626, GO:0009627, perhaps some others).  I recommend changing the word to
"microbial" or "microbe" where appropriate.

We can work out the DAG at the GO Content Meeting or after.

Thanks,

Alex


1)  Obsolete:  GO:0009613 ; response to pest, pathogen or parasite
Replace by "response to foreign biotic stimulus"
Definition:  A change in state or activity of an organism (in terms of movement,
secretion, enzyme production, gene expression, etc.) as a result of the
perception of a foreign biotic stimulus. Foreign implies recognition of non-self
components through both dedicated (TLRs etc) and adaptive (antibodies or TCRs)
components.  No distinction is made between "pathogenic" and "non-pathogenic"
bacteria etc. (Note that the meaning of "biotic stimulus" needs to be expanded
to mean any stimulus derived from a biological origin, such a soluble protein,
as well as whole cells, living or dead)


2)  Obsolete:  GO:0009596 ; detection of pest, pathogen or parasite
Replace by "detection of foreign biotic stimulus"
Definition:  The series of events by which a stimulus from a foreign biotic
stimulus is received and converted into a molecular signal.


3)  Obsolete:  GO:0009680 ; response to non-pathogenic bacteria
4)  Obsolete:  GO:0009681 ; detection of non-pathogenic bacteria
5)  Obsolete:  GO:0042828 ; response to pathogen
6)  Obsolete:  GO:0042829 ; defense response to pathogen
7)  Obsolete:  GO:0009814 ; defense response to pathogen, incompatible interaction
(replace with "defense response, incompatible interaction," defined as
"A response of an organism to a microbiotic stimulus that prevents the
occurrence or spread of the microbe.")
8)  Obsolete:  GO:0009618 ; response to pathogenic bacteria
9)  Obsolete:  GO:0009598 ; detection of pathogenic bacteria
10)  Obsolete:  GO:0042830 ; defense response to pathogenic bacteria
11)  Obsolete:  GO:0009816 ; defense response to pathogenic bacteria,
incompatible interaction
(replace with "defense response to bacteria, incompatible interaction")
12)  Obsolete:  GO:0009621 ; response to pathogenic fungi
13)  Obsolete:  GO:0009599 ; detection of pathogenic fungi
14)  Obsolete:  GO:0016047 ; detection of parasitic fungi
15)  Obsolete:  GO:0042831 ; defense response to pathogenic fungi
16)  Obsolete:  GO:0009817 ; defense response to pathogenic fungi,
incompatible interaction
(replace with "defense response to fungi, incompatible interaction")
17)  Obsolete:  GO:0042833 ; response to pathogenic protozoa
18)  Obsolete:  GO:0042832 ; defense response to pathogenic protozoa
19)  Obsolete:  GO:0009818; defense response to pathogenic protozoa,
incompatible interaction
(replace with "defense response to protozoa, incompatible interaction")
20)  Obsolete:  GO:0043019 ; response to pathogenic insects
(Definition:  "A change in state or activity of an organism (in terms of
movement, secretion, enzyme production, gene expression, etc.) as a
result of the perception of a pathogenic (disease-causing) insect."  
Personally, I kill all mosquitoes regardless of their West Nile Virus status.)
21)  Obsolete:  GO:0030383 ; host-pathogen interaction
(agree with PAMGO on this)
22)  Obsolete:  GO:0009405 ; pathogenesis
(agree with PAMGO on this)
23) GO:0012504 ; induction of non-apoptotic programmed cell death by pathogen
(currently undefined, probably best replaced by PAMGO's necrosis term)

------------------------------

14. Alex's Cell Killing Proposal and Terms

I have incorporated terms from Candace Collmer's PAMGO proposal and my own
SourceForge entry 960898 (Cytolysis Terms) into a larger cell killing DAG
intended to cover the killing of both self and foreign cells.  I feel this is
necessary to unite all mechanisms of cell killing in the GO under one larger
umbrella, and recognize that certain mechanisms such as the activation of the
terminal pathway of complement are used against both self and non-self (i.e.
what might be considered 'non host' in the PAMGO proposal) cells.  Naturally the
PAMGO hierarchy is mostly unaffected itself, except for a few term name
modifications.  The GO should be written to cover all biology from both
microbial and host perspectives, and thus a unified cell killing hierarchy is
needed. This is not intended as a finished proposal, more like a stimulus for
discussion.  But the cytotoxicity terms are sorely needed for immunology, so I
hope we can resolve this at the content meeting. Some definitions of new terms
are from PAMGO, others from SF 960898 (shown after the DAG view below), and
others from me today (listed before DAG). Sensible regulation terms and other
things may be added as needed.

-- Alex

A)  New Term:  cell killing
Definition:  Any process in an organism that results in the killing of its own
cells or those of another organism, including in some cases the death of the
other organism.
Comment:  Killing here refers to the induction of death in one cell by another
cell, not cell-autonomous death due to internal or other environmental
conditions.

B)  New Term:  cell killing, other organism (called 'cell killing' in PAMGO)
Definition:  Any process in an organism that results in the death of another
organism or its cells.

C)  New Term:  cell killing, self

Definition:  Any process in an organism that results in the killing of its own
cells.
Comment:  Killing here refers to the induction of death in one cell by another
cell, not cell-autonomous death due to internal or other environmental
conditions.

D)  New Term:  activation of the membrane attack complex

Synonym:  activation of the terminal complement cascade
Synonym:  activation of MAC
Synonym:  activation of TCC
Definition:  The activation of the membrane attack complex components of the
complement cascade which can result in death of a target cell through cytolysis.


The new DAG:

GO:0008219 ; cell death
--< GO:0007569 ; cell aging +
--% GO:0012501 ; programmed cell death +
--% GO:0010198 ; synergid cell death +
--% GO:NewTerm ; cell killing
----% GO:0019835 ; cytolysis
------< GO:0042268 ; regulation of cytolysis
--------% GO:0045918 ;  negative regulation of cytolysis
--------% GO:0045919 ; positive regulation of cytolysis
------% GO:0019835 ; cytolysis of host cells
--------% GO:0019836 ; hemolysis
------< GO:0042268 ; regulation of cytolysis of host cells
--------% GO:0045918 ;  negative regulation of cytolysis
--------% GO:0045919 ; positive regulation of cytolysis
------% GO:NewTerm ; activation of the membrane attack complex
----% GO:NewTerm ; cell killing, other organism
------% GO:NewTerm ; killing of host cells
--------% GO:0019835 ; cytolysis of host cells
----------% GO:0019836 ; hemolysis
--------< GO:0042268 ; regulation of cytolysis of host cells
----------% GO:0045918 ;  negative regulation of cytolysis
----------% GO:0045919 ; positive regulation of cytolysis
------% GO:NewTerm killing of non host cells
----% GO:NewTerm ; cell killing, self
------% GO:NewTerm ; immune cell mediated cytotoxicity
--------% GO:NewTerm ; T-cell mediated cytotoxicity
----------< GO:NewTerm ; regulation of T-cell mediated cytotoxicity
------------% GO:NewTerm ; negative regulation of T-cell mediated cytotoxicity
------------% GO:NewTerm ; positive regulation of T-cell mediated cytotoxicity
--------% GO:0042267 ; natural killer cell mediated cytotoxicity [as renamed]
----------< GO:0042269 ; regulation of natural killer cell mediated cytotoxicity [as renamed]
------------% GO:0045953 ; negative regulation of natural killer cell mediated cytotoxicity [as renamed]
--------------% GO:0042270 ; protection from natural killer cell mediated cytotoxicity [as renamed]
------------% GO:0045954 ; positive regulation of natural killer cell mediated cytotoxicity [as renamed]
--------------% GO:0042271 ; susceptibility to natural killer cell mediated cytotoxicity [as renamed]
--------% GO:0001788 ; antibody-dependent cellular cytotoxicity
----------< GO:0001813 ; regulation of antibody-dependent cellular cytotoxicity
------------% GO:0001814 ; negative regulation of antibody-dependent cellular cytotoxicity
------------% GO:0001815 ; positive regulation of antibody-dependent cellular cytotoxicity
--------< GO:NewTerm ; regulation of immune cell mediated cytotoxicity
----------% GO:NewTerm ; negative regulation of immune cell mediated cytotoxicity
------------% GO:NewTerm ; negative regulation of T-cell mediated cytotoxicity
------------% GO:0045953 ; negative regulation of natural killer cell mediated cytotoxicity [as renamed]
--------------% GO:0042270 ; protection from natural killer cell mediated cytotoxicity [as renamed]
------------% GO:0001814 ; negative regulation of antibody-dependent cellular cytotoxicity
----------% GO:NewTerm ; positive regulation of immune cell mediated cytotoxicity
------------% GO:NewTerm ; positive regulation of T-cell mediated cytotoxicity
------------% GO:0045954 ; positive regulation of natural killer cell mediated cytotoxicity [as renamed]
--------------% GO:0042271 ; susceptibility to natural killer cell mediated cytotoxicity [as renamed]
------------% GO:0001815 ; positive regulation of antibody-dependent cellular cytotoxicity
----------% GO:NewTerm ; regulation of T-cell mediated cytotoxicity
------------% GO:NewTerm ; negative regulation of T-cell mediated cytotoxicity
------------% GO:NewTerm ; positive regulation of T-cell mediated cytotoxicity
----------% GO:0042269 ; regulation of natural killer cell mediated cytotoxicity [as renamed]
--------------% GO:0045953 ; negative regulation of natural killer cell mediated cytotoxicity [as renamed]
----------------% GO:0042270 ; protection from natural killer cell mediated cytotoxicity [as renamed]
--------------% GO:0045954 ; positive regulation of natural killer cell mediated cytotoxicity [as renamed]
----------------% GO:0042271 ; susceptibility to natural killer cell mediated cytotoxicity [as renamed]
------------% GO:0001813 ; regulation of antibody-dependent cellular cytotoxicity
--------------% GO:0001814 ; negative regulation of antibody-dependent cellular cytotoxicity
--------------% GO:0001815 ; positive regulation of antibody-dependent cellular cytotoxicity


The terms from SF 960898 (as revised in that thread):

1)  New Term:  immune cell mediated cytotoxicity
Synonym:  immune cell mediated cell killing [=]
Synonym:  immune cell mediated cell death [=]
Definition:  The directed killing of a target cell by a by an immune cell.
Parentage:  is-a to GO:0008219 cell death and is-a to GO:0042087
cell-mediated immune response.
Comment:  This term and its children are meant to describe
contact-dependent killing of target cells by lymphocytes and
myeloid cells of the immune system.
Reference:  ISBN:0781735149, PMID:11911826


2)  New term:  regulation of immune cell mediated cytotoxicity
Synonym:  regulation of immune cell mediated cell killing [=]
Synonym:  regulation of immune cell mediated cell death [=]
Definition:  Any process that modulates the frequency, rate, or
extent of immune cell mediated cytotoxicity.
Parentage:  part-of to "immune cell mediated cytotoxicity," above
Reference:  ISBN:0781735149, PMID:11911826


3)  New term:  negative regulation of immune cell mediated cytotoxicity
Synonym:  negative regulation of immune cell mediated cell killing [=]
Synonym:  negative regulation of immune cell mediated cell death [=]
Definition:  Any process that stops, prevents, or reduces the rate of
immune cell mediated cytotoxicity.
Parentage:  is-a to "regulation of immune cell mediated cytotoxicity," above
Reference:  ISBN:0781735149, PMID:11911826

4)  New term:  positive regulation of immune cell mediated cytotoxicity
Synonym:  positive regulation of immune cell mediated cell killing [=]
Synonym:  positive regulation of immune cell mediated cell death [=]
Definition:  Any process that activates or increases the rate of immune
cell mediated cytotoxicity.
Parentage:  is-a to "regulation of immune cell mediated cytotoxicity," above
Reference:  ISBN:0781735149, PMID:11911826
 
5)  New Term: T-cell mediated cytotoxicity
Synonym:  T cell mediated cytotoxicity [=]
Synonym:  T-cell mediated apoptosis [=]
Synonym:  T cell mediated apoptosis [=]
Synonym:  T-cell mediated cell killing [=]
Synonym:  T cell mediated cell killing [=]
Synonym:  T-cell mediated cell death [=]
Synonym:  T cell mediated cell death [=]
Synonym:  T-cell mediated cytolysis [~]
Synonym:  T cell mediated cytolysis [~]

Definition:  The directed killing of a target cell by a T-cell through the
release of granules containing cytotoxic mediators or through the engagement of
death receptors.
Parentage:  is-a to immune cell mediated cytotoxicity and is-a to GO:00069174
induction of apoptosis.
Comment:  Note that either or both mechanisms mentioned in the definition may be
used in this process.
Comment:  Note that both granule release and the engagement of death receptors
on target cells result in the induction of apoptosis in the target cell.
Comment:  Note that both CD4 and CD8 positive T-cells can mediate apoptosis of
target cells, independently of their definition as "helper" T-cells or not.
Reference:  ISBN:0781735149, PMID:11911826

[Editorial note:  although isolated perforin has been shown to induce cytolysis
directly when applied to target cells at high concentrations, experimental
evidence shows that the function of perforin is to allow access of granzymes
into the cytoplasm of the target cell, followed by the granzyme mediated
cleavage of caspase and non-caspase components of the apoptotic pathway leading
to the induction of apoptosis.]


6)  New Term:  regulation of T-cell mediated cytotoxicity
Synonym:  regulation of T cell mediated cytotoxicity [=]
Synonym:  regulation of T-cell mediated apoptosis [=]
Synonym:  regulation of T cell mediated apoptosis [=]
Synonym:  regulation of T cell mediated cell killing [=]
Synonym:  regulation of T-cell mediated cell killing [=]
Synonym:  regulation of T-cell mediated cell death [=]
Synonym:  regulation of T cell mediated cell death [=]
Synonym:  regulation of T-cell mediated cytolysis [~]
Synonym:  regulation of T cell mediated cytolysis [~]
Definition:  Any process that modulates the frequency, rate, or extent of T-cell
mediated cytotoxicity.
Parentage:  part-of to "T-cell mediated cytotoxicity" and is-a to "regulation of
immune cell mediated cytotoxicity," above.
Reference:  ISBN:0781735149

7)  New Term:  negative regulation of T-cell mediated cytotoxicity
Synonym:  negative regulation of T cell mediated cytotoxicity [=]
Synonym:  negative regulation of T-cell mediated apoptosis [=]
Synonym:  negative regulation of T cell mediated apoptosis [=]
Synonym:  negative regulation of T cell mediated cell killing [=]
Synonym:  negative regulation of T-cell mediated cell killing [=]
Synonym:  negative regulation of T-cell mediated cell death [=]
Synonym:  negative regulation of T cell mediated cell death [=]
Synonym:  negative regulation of T-cell mediated cytolysis [~]
Synonym:  negative regulation of T cell mediated cytolysis [~]
Definition:  Any process that stops, prevents, or reduces the rateof T-cell
mediated cytotoxicity.
Parentage:  is-a to "regulation of T-cell mediated cytotoxicity" and is-a to
"negative regulation of immune cell mediated cytotoxicity," above.
Reference:  ISBN:0781735149

8)  New Term:  positive regulation of T-cell mediated cytotoxicity
Synonym:  positive regulation of T cell mediated cytotoxicity [=]
Synonym:  positive regulation of T-cell mediated apoptosis [=]
Synonym:  positive regulation of T cell mediated apoptosis [=]
Synonym:  positive regulation of T cell mediated cell killing [=]
Synonym:  positive regulation of T-cell mediated cell killing [=]
Synonym:  positive regulation of T-cell mediated cell death [=]
Synonym:  positive regulation of T cell mediated cell death [=]
Synonym:  positive regulation of T-cell mediated cytolysis [~]
Synonym:  positive regulation of T cell mediated cytolysis [~]
Definition:  Any process that activates or increases the rate of T-cell mediated
cytotoxicity.
Parentage:  is-a to "regulation of T-cell mediated cytotoxicity" and is-a to
"positive regulation of immune cell mediated cytotoxicity," above.
Reference:  ISBN:0781735149
 
9)  GO:0042267 natural killer cell mediated cytolysis
This term needs to be renamed and redefined to parallel the T-cell mediated cytotoxicity term, because the mechanisms of cell killing used by NK cells are nearly identical to those of T cells, and involve the induction of apoptosis in the target cells.
Proposed new name:  natural killer cell mediated cytotoxicity
Synonym (new):  NK cell mediated cytotoxicity [=]
Synonym (new):  natural killer cell mediated cytolysis [~]
Synonym (old):  NK cell mediated cytolysis [~]
Synonym (old):  natural killer-cell mediated cytolysis [~]
|Proposed new definition:  The directed killing of a target cell by a natural killer cell through the release of granules containing cytotoxic mediators or through the engagement of death receptors.
Revised parentage:  is-a to "immune cell mediated cytotoxicity," above, and is-a to GO:00069174 induction of apoptosis
Comment:  Note that either or both mechanisms mentioned in the definition may be used in this process.

Comment:  Note that both granule release and the engagement of death receptors on target cells result in induction of apoptosis in the target cell.

10)  GO:0042269 regulation of natural killer cell mediated cytolysis
Proposed new name:  regulation of natural killer cell mediated cytotoxicity
Synonym (new):  regulation of NK cell mediated cytotoxicity [=]
Synonym (new):  regulation of natural killer cell mediated cytolysis [~]
Synonym (old):  regulation of NK cell mediated cytolysis [~]
Synonym (old):  regulation of natural killer-cell mediated cytolysis [~]
Proposed new definition:  Any process that modulates the frequency, rate, or extent of natural killer cell mediated cytotoxicity.
Revised parentage:  part-of to GO:0042267 natural killer cell mediated cytotoxicity [as renamed] and to "regulation of immune cell mediated cytotoxicity," above.
Reference:  ISBN:0781735149

11)  GO:0045953 negative regulation of natural killer cell mediated cytolysis
Proposed new name:  negative regulation of natural killer cell mediated cytotoxicity
Synonym (new): negative regulation of NK cell mediated cytotoxicity [=]
Synonym (new):  negative regulation of natural killer cell mediated cytolysis [~]
Synonym (old):  negative regulation of NK cell mediated cytolysis [~]
Proposed new definition:  Any process that stops, prevents, or reduces the rate of natural killer mediated cytotoxicity.
Revised parentage:  is-a to GO:0042269 regulation of natural killer cell mediated cytotoxicity [as renamed] and to "negative regulation of immune cell mediated cytotoxicity," above.
Reference:  ISBN:0781735149

12)  GO:0045954 positive regulation of natural killer cell mediated cytolysis
Proposed new name:  positive regulation of natural killer cell mediated cytotoxicity
Synonym (new):  positive regulation of NK cell mediated cytotoxicity [=]
Synonym (new):  positive regulation of natural killer cell mediated cytolysis [~]
Synonym (old):  positive regulation of NK cell mediated cytolysis [~]
Proposed new definition:  Any process that activates or increases the rate of natural killer cell mediated cytotoxicity.
Revised parentage:  is-a to GO:0042269 regulation of natural killer cell mediated cytotoxicity [as renamed] and to "positive regulation of immune cell mediated cytotoxicity," above.
Reference:  ISBN:0781735149

13)  GO:0042270 protection from natural killer cell mediated cytolysis
Proposed new name:  protection from natural killer cell mediated cytotoxicity
Synonym (new):  protection from NK cell mediated cytotoxicity [=]
Synonym (new):  protection from natural killer cell mediated cytolysis [~]
Synonym (old):  protection from NK cell mediated cytolysis [~]
Proposed new definition:  The process of protecting a cell from natural killer cell mediated cytotoxicity.
Revised parentage:  is-a to GO:0045953 negative regulation of natural killer cell mediated cytotoxicity [as renamed above].
Comment:  Note that this term is intended for cell-surface molecules on a target cell which interact with inhibitory receptors on a natural killer cell to prevent natural killer cell mediated cytotoxicity.
[Editorial note:  This is clearly a type of negative regulation of NK cell cytotoxicity and its position in the DAG should reflect that.]

14)  GO:0042271 susceptibility to natural killer cell mediated cytolysis
Proposed new name: susceptibility to natural killer cell mediated cytotoxicity
Synonym (new): susceptibility to NK cell mediated cytotoxicity [=]
Synonym (new): susceptibility to natural killer cell mediated cytolysis [~]
Synonym (old): susceptibility to NK cell mediated cytolysis [~]
Proposed new definition:  The process of causing a cell to become susceptible to natural killer cell mediated cytotoxicity.
Revised parentage:  is-a to GO:0045954 positive regulation of natural killer cell mediated cytotoxicity [as renamed above].
Comment:  Note that this term is intended for cell-surface molecules on a target cell which interact with activating receptors on a natural killer cell to promote natural killer cell mediated cytotoxicity.
[Editorial note:  This is clearly a type of positive regulation of NK cell cytotoxicity and its position in the DAG should reflect that.]

15)  GO:0001788 antibody-dependent cellular cytotoxicity
Proposed new definition:  Killing of target cells by natural killer cells, eosinophils, neutrophils, monocytes, or macrophages following engagement of antibodies bound to the target cells by Fc receptors on the effector cells.
Revised parentage:  is-a to "immune cell mediated cytotoxicity," above, and is-a to GO:00069174 induction of apoptosis

16)  GO:0001813 regulation of antibody-dependent cellular cytotoxicity
Revised parentage:  part-of to GO:0001788 antibody-dependent cellular cytotoxicity and is-a to "regulation of immune cell mediated cytotoxicity," above.

17)  GO:0001814 negative regulation of antibody-dependent cellular cytotoxicity
Revised parentage:  is-a to GO:0001813 regulation of antibody- dependent cellular cytotoxicity and is-a to "negative regulation of immune cell mediated cytotoxicity," above.

18)  GO:0001815 positive regulation of antibody-dependent cellular cytotoxicity
Revised parentage:  is-a to GO:0001813 regulation of antibody- dependent cellular cytotoxicity and is-a to "positive regulation of immune cell mediated cytotoxicity," above.

--------------------------------

15. Cell Killing Terms incorporating the discussion at the GO Content meeting

I have made changes to the DAG and terms according to the discussion at the GO content meeting (including the elimination of the term "cell killing, self").  However, I am still unsure of how to rename the PAMGO term "killing of non host cells," and whether the term "cytolysis of non-host cells" and its children need to be created.

Additional comments are welcome,

Alex


A)  New Term:  cell killing
Definition:  Any process in an organism that results in the killing of its own cells or those of another organism, including in some cases the death of the other organism.  Killing here refers to the induction of death in one cell by another cell, not cell-autonomous death due to internal or other environmental conditions.

B)  New Term:  cell killing, other organism (called 'cell killing' in PAMGO)
Definition:  Any process in an organism that results in the death of another organism or its cells.

C)  New Term:  activation of the membrane attack complex
Synonym:  activation of the terminal complement cascade
Synonym:  activation of MAC
Synonym:  activation of TCC
Definition:  The activation of the membrane attack complex components of the complement cascade which can result in death of a target cell through cytolysis.

D)  New Term:  autolysis
Definition:  The spontaneous death by lysis of bacteria in response to environmental conditions.

The revised DAG:

GO:0008219 ; cell death
--< GO:0007569 ; cell aging +
--% GO:0012501 ; programmed cell death +
--% GO:0010198 ; synergid cell death +
--% GO:0019835 ; cytolysis
----% GO:NewTerm ; autolysis
----< GO:0042268 ; regulation of cytolysis
------% GO:0045918 ; negative regulation of cytolysis
------% GO:0045919 ; positive regulation of cytolysis
----% GO:NewTerm ; cytolysis of host cells
------% GO:0019836 ; hemolysis
------< GO:NewTerm ; regulation of cytolysis of host cells
--------% GO:NewTerm ;  negative regulation of cytolysis of host cells
--------% GO:NewTerm ; positive regulation of cytolysis of host cells
----% GO:NewTerm ; cytolysis of non host cells
------< GO:NewTerm ; regulation of cytolysis of non host cells
--------% GO:NewTerm ;  negative regulation of cytolysis of non host cells
--------% GO:NewTerm ; positive regulation of cytolysis non host cells
----% GO:NewTerm ; activation of the membrane attack complex
--% GO:NewTerm ; cell killing
----% GO:NewTerm ; cell killing, other organism
------% GO:NewTerm ; killing of host cells
--------% GO:NewTerm ; cytolysis of host cells
----------% GO:0019836 ; hemolysis
----------< GO:NewTerm ; regulation of cytolysis of host cells
------------% GO:NewTerm ;  negative regulation of cytolysis of host cells
------------% GO:NewTerm ; positive regulation of cytolysis host cells
------% GO:NewTerm killing of non host cells
--------% GO:NewTerm ; cytolysis of non host cells
----------< GO:NewTerm ; regulation of cytolysis of non host cells
------------% GO:NewTerm ;  negative regulation of cytolysis of non host cells
------------% GO:NewTerm ; positive regulation of cytolysis non host cells
----% GO:NewTerm ; immune cell mediated cytotoxicity
------% GO:NewTerm ; T-cell mediated cytotoxicity
--------< GO:NewTerm ; regulation of T-cell mediated cytotoxicity
----------% GO:NewTerm ; negative regulation of T-cell mediated cytotoxicity
----------% GO:NewTerm ; positive regulation of T-cell mediated cytotoxicity
------% GO:0042267 ; natural killer cell mediated cytotoxicity [as renamed]
--------< GO:0042269 ; regulation of natural killer cell mediated cytotoxicity [as renamed]
----------% GO:0045953 ; negative regulation of natural killer cell mediated cytotoxicity [as renamed]
------------% GO:0042270 ; protection from natural killer cell mediated cytotoxicity [as renamed]
----------% GO:0045954 ; positive regulation of natural killer cell mediated cytotoxicity [as renamed]
------------% GO:0042271 ; susceptibility to natural killer cell mediated cytotoxicity [as renamed]
------% GO:0001788 ; antibody-dependent cellular cytotoxicity
--------< GO:0001813 ; regulation of antibody-dependent cellular cytotoxicity
----------% GO:0001814 ; negative regulation of antibody-dependent cellular cytotoxicity
----------% GO:0001815 ; positive regulation of antibody-dependent cellular cytotoxicity
------< GO:NewTerm ; regulation of immune cell mediated cytotoxicity
--------% GO:NewTerm ; negative regulation of immune cell mediated cytotoxicity
----------% GO:NewTerm ; negative regulation of T-cell mediated cytotoxicity
----------% GO:0045953 ; negative regulation of natural killer cell mediated cytotoxicity [as renamed]
------------% GO:0042270 ; protection from natural killer cell mediated cytotoxicity [as renamed]
----------% GO:0001814 ; negative regulation of antibody-dependent cellular cytotoxicity
--------% GO:NewTerm ; positive regulation of immune cell mediated cytotoxicity
----------% GO:NewTerm ; positive regulation of T-cell mediated cytotoxicity
----------% GO:0045954 ; positive regulation of natural killer cell mediated cytotoxicity [as renamed]
------------% GO:0042271 ; susceptibility to natural killer cell mediated cytotoxicity [as renamed]
----------% GO:0001815 ; positive regulation of antibody-dependent cellular cytotoxicity
--------% GO:NewTerm ; regulation of T-cell mediated cytotoxicity
----------% GO:NewTerm ; negative regulation of T-cell mediated cytotoxicity
----------% GO:NewTerm ; positive regulation of T-cell mediated cytotoxicity
--------% GO:0042269 ; regulation of natural killer cell mediated cytotoxicity [as renamed]
----------% GO:0045953 ; negative regulation of natural killer cell mediated cytotoxicity [as renamed]
------------% GO:0042270 ; protection from natural killer cell mediated cytotoxicity [as renamed]
----------% GO:0045954 ; positive regulation of natural killer cell mediated cytotoxicity [as renamed]
------------% GO:0042271 ; susceptibility to natural killer cell mediated cytotoxicity [as renamed]
--------% GO:0001813 ; regulation of antibody-dependent cellular cytotoxicity
----------% GO:0001814 ; negative regulation of antibody-dependent cellular cytotoxicity
----------% GO:0001815 ; positive regulation of antibody-dependent cellular cytotoxicity


The terms from SF 960898 (as revised in that thread):

1)  New Term:  immune cell mediated cytotoxicity
Synonym:  immune cell mediated cell killing [=]
Synonym:  immune cell mediated cell death [=]
Definition:  The directed killing of a target cell by a by an immune cell.
Parentage:  is-a to GO:0008219 cell death and is-a to GO:0042087 cell-mediated
immune response.
Comment:  This term and its children are meant to describe contact-dependent
killing of target cells by lymphocytes and myeloid cells of the immune system.
Reference:  ISBN:0781735149, PMID:11911826


2)  New term:  regulation of immune cell mediated cytotoxicity
Synonym:  regulation of immune cell mediated cell killing [=]
Synonym:  regulation of immune cell mediated cell death [=]
Definition:  Any process that modulates the frequency, rate, or extent of immune
cell mediated cytotoxicity.
Parentage:  part-of to "immune cell mediated cytotoxicity," above
Reference:  ISBN:0781735149, PMID:11911826


3)  New term:  negative regulation of immune cell mediated cytotoxicity
Synonym:  negative regulation of immune cell mediated cell killing [=]
Synonym:  negative regulation of immune cell mediated cell death [=]
Definition:  Any process that stops, prevents, or reduces the rate of immune
cell mediated cytotoxicity.
Parentage:  is-a to "regulation of immune cell mediated cytotoxicity," above
Reference:  ISBN:0781735149, PMID:11911826

4)  New term:  positive regulation of immune cell mediated cytotoxicity
Synonym:  positive regulation of immune cell mediated cell killing [=]
Synonym:  positive regulation of immune cell mediated cell death [=]
Definition:  Any process that activates or increases the rate of immune cell
mediated cytotoxicity.
Parentage:  is-a to "regulation of immune cell mediated cytotoxicity," above
Reference:  ISBN:0781735149, PMID:11911826

5)  New Term: T-cell mediated cytotoxicity
Synonym:  T cell mediated cytotoxicity [=]
Synonym:  T-cell mediated apoptosis [=]
Synonym:  T cell mediated apoptosis [=]
Synonym:  T-cell mediated cell killing [=]
Synonym:  T cell mediated cell killing [=]
Synonym:  T-cell mediated cell death [=]
Synonym:  T cell mediated cell death [=]
Synonym:  T-cell mediated cytolysis [~]
Synonym:  T cell mediated cytolysis [~]
Definition:  The directed killing of a target cell by a T-cell through the
release of granules containing cytotoxic mediators or through the engagement of
death receptors.
Parentage:  is-a to immune cell mediated cytotoxicity and is-a to GO:00069174
induction of apoptosis.
Comment:  Note that either or both mechanisms mentioned in the definition may be
used in this process.
Comment:  Note that both granule release and the engagement of death receptors
on target cells result in the induction of apoptosis in the target cell.
Comment:  Note that both CD4 and CD8 positive T-cells can mediate apoptosis of
target cells, independently of their definition as "helper" T-cells or not.
Reference:  ISBN:0781735149, PMID:11911826
[Editorial note:  although isolated perforin has been shown to induce cytolysis
directly when applied to target cells at high concentrations, experimental
evidence shows that the function of perforin is to allow access of granzymes
into the cytoplasm of the target cell, followed by the granzyme mediated
cleavage of caspase and non-caspase components of the apoptotic pathway leading
to the induction of apoptosis.]

6)  New Term:  regulation of T-cell mediated cytotoxicity
Synonym:  regulation of T cell mediated cytotoxicity [=]
Synonym:  regulation of T-cell mediated apoptosis [=]
Synonym:  regulation of T cell mediated apoptosis [=]
Synonym:  regulation of T cell mediated cell killing [=]
Synonym:  regulation of T-cell mediated cell killing [=]
Synonym:  regulation of T-cell mediated cell death [=]
Synonym:  regulation of T cell mediated cell death [=]
Synonym:  regulation of T-cell mediated cytolysis [~]
Synonym:  regulation of T cell mediated cytolysis [~]
Definition:  Any process that modulates the frequency, rate, or extent of T-cell
mediated cytotoxicity.
Parentage:  part-of to "T-cell mediated cytotoxicity" and is-a to "regulation of
immune cell mediated cytotoxicity," above.
Reference:  ISBN:0781735149

7)  New Term:  negative regulation of T-cell mediated cytotoxicity
Synonym:  negative regulation of T cell mediated cytotoxicity [=]
Synonym:  negative regulation of T-cell mediated apoptosis [=]
Synonym:  negative regulation of T cell mediated apoptosis [=]
Synonym:  negative regulation of T cell mediated cell killing [=]
Synonym:  negative regulation of T-cell mediated cell killing [=]
Synonym:  negative regulation of T-cell mediated cell death [=]
Synonym:  negative regulation of T cell mediated cell death [=]
Synonym:  negative regulation of T-cell mediated cytolysis [~]
Synonym:  negative regulation of T cell mediated cytolysis [~]
Definition:  Any process that stops, prevents, or reduces the rate of T-cell
mediated cytotoxicity.
Parentage:  is-a to "regulation of T-cell mediated cytotoxicity" and is-a to
"negative regulation of immune cell mediated cytotoxicity," above.
Reference:  ISBN:0781735149

8)  New Term:  positive regulation of T-cell mediated cytotoxicity
Synonym:  positive regulation of T cell mediated cytotoxicity [=]
Synonym:  positive regulation of T-cell mediated apoptosis [=]
Synonym:  positive regulation of T cell mediated apoptosis [=]
Synonym:  positive regulation of T cell mediated cell killing [=]
Synonym:  positive regulation of T-cell mediated cell killing [=]
Synonym:  positive regulation of T-cell mediated cell death [=]
Synonym:  positive regulation of T cell mediated cell death [=]
Synonym:  positive regulation of T-cell mediated cytolysis [~]
Synonym:  positive regulation of T cell mediated cytolysis [~]
Definition:  Any process that activates or increases the rate of T-cell mediated
cytotoxicity.
Parentage:  is-a to "regulation of T-cell mediated cytotoxicity" and is-a to
"positive regulation of immune cell mediated cytotoxicity," above.
Reference:  ISBN:0781735149

9)  GO:0042267 natural killer cell mediated cytolysis
This term needs to be renamed and redefined to parallel the T-cell mediated
cytotoxicity term, because the mechanisms of cell killing used by NK cells are
nearly identical to those of T cells, and involve the induction of apoptosis in
the target cells.
Proposed new name:  natural killer cell mediated cytotoxicity
Synonym (new):  NK cell mediated cytotoxicity [=]
Synonym (new):  natural killer cell mediated cytolysis [~]
Synonym (old):  NK cell mediated cytolysis [~]
Synonym (old):  natural killer-cell mediated cytolysis [~]
Proposed new definition:  The directed killing of a target cell by a natural
killer cell through the release of granules containing cytotoxic mediators or
through the engagement of death receptors.
Revised parentage:  is-a to "immune cell mediated cytotoxicity," above, and is-a
to GO:00069174 induction of apoptosis
Comment:  Note that either or both mechanisms mentioned in the definition may be
used in this process.
Comment:  Note that both granule release and the engagement of death receptors
on target cells result in induction of apoptosis in the target cell.

10)  GO:0042269 regulation of natural killer cell mediated cytolysis

Proposed new name:  regulation of natural killer cell mediated cytotoxicity
Synonym (new):  regulation of NK cell mediated cytotoxicity [=]
Synonym (new):  regulation of natural killer cell mediated cytolysis [~]
Synonym (old):  regulation of NK cell mediated cytolysis [~]
Synonym (old):  regulation of natural killer-cell mediated cytolysis [~]
Proposed new definition:  Any process that modulates the frequency, rate, or
extent of natural killer cell mediated cytotoxicity.
Revised parentage:  part-of to GO:0042267 natural killer cell mediated
cytotoxicity [as renamed] and to "regulation of immune cell mediated
cytotoxicity," above.
Reference:  ISBN:0781735149

11)  GO:0045953 negative regulation of natural killer cell mediated cytolysis
Proposed new name:  negative regulation of natural killer cell mediated cytotoxicity
Synonym (new): negative regulation of NK cell mediated cytotoxicity [=]
Synonym (new):  negative regulation of natural killer cell mediated cytolysis [~]
Synonym (old):  negative regulation of NK cell mediated cytolysis [~]
Proposed new definition:  Any process that stops, prevents, or reduces the rate
of natural killer mediated cytotoxicity.
Revised parentage:  is-a to GO:0042269 regulation of natural killer cell
mediated cytotoxicity [as renamed] and to "negative regulation of immune cell
mediated cytotoxicity," above.
Reference:  ISBN:0781735149

12)  GO:0045954 positive regulation of natural killer cell mediated cytolysis
Proposed new name:  positive regulation of natural killer cell mediated cytotoxicity
Synonym (new):  positive regulation of NK cell mediated cytotoxicity [=]
Synonym (new):  positive regulation of natural killer cell mediated cytolysis [~]
Synonym (old):  positive regulation of NK cell mediated cytolysis [~]
Proposed new definition:  Any process that activates or increases the rate of
natural killer cell mediated cytotoxicity.
Revised parentage:  is-a to GO:0042269 regulation of natural killer cell
mediated cytotoxicity [as renamed] and to "positive regulation of immune cell
mediated cytotoxicity," above.
Reference:  ISBN:0781735149

13)  GO:0042270 protection from natural killer cell mediated cytolysis
Proposed new name:  protection from natural killer cell mediated cytotoxicity
Synonym (new):  protection from NK cell mediated cytotoxicity [=]
Synonym (new):  protection from natural killer cell mediated cytolysis [~]
Synonym (old):  protection from NK cell mediated cytolysis [~]
Proposed new definition:  The process of protecting a cell from natural killer
cell mediated cytotoxicity.
Revised parentage:  is-a to GO:0045953 negative regulation of natural killer
cell mediated cytotoxicity [as renamed above].
Comment:  Note that this term is intended for cell-surface molecules on a target
cell which interact with inhibitory receptors on a natural killer cell to
prevent natural killer cell mediated cytotoxicity.
[Editorial note:  This is clearly a type of negative regulation of NK cell
cytotoxicity and its position in the DAG should reflect that.]

14)  GO:0042271 susceptibility to natural killer cell mediated cytolysis
Proposed new name: susceptibility to natural killer cell mediated cytotoxicity
Synonym (new): susceptibility to NK cell mediated cytotoxicity [=]
Synonym (new): susceptibility to natural killer cell mediated cytolysis [~]
Synonym (old): susceptibility to NK cell mediated cytolysis [~]
Proposed new definition:  The process of causing a cell to become susceptible to
natural killer cell mediated cytotoxicity.
Revised parentage:  is-a to GO:0045954 positive regulation of natural killer
cell mediated cytotoxicity [as renamed above].
Comment:  Note that this term is intended for cell-surface molecules on a target
cell which interact with activating receptors on a natural killer cell to
promote natural killer cell mediated cytotoxicity.
[Editorial note:  This is clearly a type of positive regulation of NK cell
cytotoxicity and its position in the DAG should reflect that.]

15)  GO:0001788 antibody-dependent cellular cytotoxicity
Proposed new definition:  Killing of target cells by natural killer cells,
eosinophils, neutrophils, monocytes, or macrophages following engagement of
antibodies bound to the target cells by Fc receptors on the effector cells.
Revised parentage:  is-a to "immune cell mediated cytotoxicity," above, and is-a
to GO:00069174 induction of apoptosis

16)  GO:0001813 regulation of antibody-dependent cellular cytotoxicity
Revised parentage:  part-of to GO:0001788 antibody-dependent cellular
cytotoxicity and is-a to "regulation of immune cell mediated cytotoxicity,"
above.

17)  GO:0001814 negative regulation of antibody-dependent cellular cytotoxicity
Revised parentage:  is-a to GO:0001813 regulation of antibody-dependent cellular
cytotoxicity and is-a to "negative regulation of immune cell mediated
cytotoxicity," above.

18)  GO:0001815 positive regulation of antibody-dependent cellular cytotoxicity
Revised parentage:  is-a to GO:0001813 regulation of antibody-dependent cellular
cytotoxicity and is-a to "positive regulation of immune cell mediated
cytotoxicity," above.

-------------------------------------

16. Suparna's proposl on host-pathogen interactions. (url)

ftp://ftp.geneontology.org/pub/go/meeting/minutes/20040822_Stanford_Content/host-pathogen_proposal.doc
ftp://ftp.geneontology.org/pub/go/meeting/minutes/20040822_Stanford_Content/host-pathogen_proposal.pdf