Virus ontology devt July 2012
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- BM got the go ahead to work on this for the month of July 2012, so that started the project again
- we need to fix the existing terms & relationships as well as add additional terms
- Incorporating some MeGO terms
- Jane Lomax, Rebecca Foulger, Brenley McIntosh
- July - devt
- July 31st - 9am EST
- Skype call to discuss
- Aug 2nd - 8am EST
- Skype call to discuss
- Aug 9th - 8am EST
- Skype again
Topics for Aug 9th discussion
- NEVER obsolete holin activity & antiholin activity terms please.
Topics to cover for Aug 2nd discussion
- new terms from BM
- BM made transpososome, intasome, resolvasome, relaxosome complex terms, but should they all be grouped under recombination complex type term?
- terminase activity (under GO:0015616)
- viral membranes -- referred to by both camps (internal & external membranes)
- capsid morphogenesis via nucleation? (TMV, HIV, L-A from yeast, MS2, etc)
- RNA translocation terms ok?
- replication tactics by viruses
Issues with current GO schema
- holin, antiholin, spanin, etc.
- structural molecule activities
- proteins that get injected... can be in tegument (Herpes) or in head
- in the world of viruses, there are structural proteins & nonstructural proteins
Structural proteins make up core/capsid Nonstructural proteins have activities which are crucial for packaging and replication of the viral genome.
Ontology cleanup & questions
- under binding, there is GO:0043498 cell surface binding (and its children bact cell surf bind & euk cell surf bind), then GO:0046812 host cell surface binding and GO:0001530 lipopolysaccharide binding.
- where is archaea cell surf bind?
- how are these terms not related? (Viruses bind all 3)
obsolete GO:0043498 and its children add child to GO:0046812 of host cell surface binding by virus or change the current term to include virus
- GO:0008907 integrase activity & GO:0008979 prophage integrase activity
- how are these diff other than a SO item?
problem with relationships between integrase being under cellular process currently change to integrase activity involved in viral ....
- GO:0000150 recombinase activity has child GO:0009009 site-specific recombinase activity.
- first, can we use this to fix transposases? (children would be serine-based and tyrosine-based transposase, with child under tyrosine of Y2 transposase activity)
- second, can we add non-site-specific recombinase activity with child DDE-based recombinase activity + child under GO:0009009 serine-based recombinase activity?
- Things BM is stuck on again:
- exactly what is the difference btwn rolling circle transposition & conservative transposition?!
- term for post-segregational killing?
Jane - killing by virus of host cell by post-segregational killing. add comment - occurs after plasmid partitioning under GO:0001907
- how do we handle exclusion? ('altruistic' -- doubly infected cells are killed) functions under GO:0039507 suppression by virus of host molecular function?
- definition for GO:0005727 doesn't really work
- are the capsid terms I have ok with the wacky viruses (i.e. 5 morphologies of archaeoviruses)?
should be. still question of dealing with core & outer capsid protein shells (Rotaviruses)
- GO:0075529 establishment of latency as a circular episome
- How do GO:0046739 spread of virus in host & GO:0019089 transmission of virus & GO:0046794 virion transport relate?
need to change GO:0046729 to spread of virus in multicellular host phages would be annotated to transmission of virus and not spread of virus in multicellular host
- How are we handling DNA replication being a cellular macromolecule biosynthetic process & is that why GO:0019081 viral protein biosynthetic process is its own term even though the syn of viral proteins isn't different from any other form of protein syn???
- I made structural molecule activity terms for virus proteins, but if we are going to obsolete them, is this bad???
these are ok
- Is it bad that viral procapsid is under virion in CC tree?
- Can I just say GO:0009405 sucks?!?!?!
get examples for children
- How do we handle Reoviruses (Rotaviruses) that have 2 concentric protein shells comprising its capsid? Ditto for phi6...
Topics to cover for July 31st discussion
- 54 terms BM added to GO (some from MeGO, but not all)
- BM rearranged a BUNCH of relationships
- BM put in new MeGO dbxrefs for ~50 existing terms in GO
- Things BM needs help with:
- Where does restriction alleviation fit? (GO:0019048 virus-host interaction)
- Change GO:0019049 evasion of host defenses by virus to suppression of ""
DONE (Becky). Changed to match parents and definition: evasion by virus of host immune response ; GO:0030683 evasion of host defenses by virus ; GO:0019049 > evasion or tolerance by virus of host immune response ; GO:0030683 evasion or tolerance of host defenses by virus ; GO:0019049
- Where does lysis inhibition fit? (established virus vs newly-infecting virus in host?!)
- response to virus -- suppression by virus of host cell lysis in response to superinfecting virus
- Where does immunity fit? (lysogenized host is immune to superinfection)
- add in immunity to viral latency definition
- Jane has the latency terms
DONE (Jane). Added a whole bunch of new terms under 'viral latency ; GO:0019042' and fixed up defs etc.
- Where does exclusion fit? (2 different viruses in same cell at same time = ONLY get progeny from 1)
- BM will look into this & we will talk about it on Thurs
- Are the MeGO terms for secretion system parts necessary?
- No. Becky will add type V ss complex terms
DONE. Added: type V protein secretion system complex ; GO:0098046
- BM will look into shared parts of the ss
- Do we want the specific children for the terminases, invertases, excisionases?
- Becky will fix relationships for recombinases
NOT DONE IN THE END (Becky). I was going to add recombinase activity ; GO:0000150 --[isa]site-specific recombinase activity ; GO:0009009 BUT, the comment of GO:0009009 states: Note that this term is not a child of 'recombinase activity ; GO:0000150' because the latter represents activities that do not break or form phosphodiester bonds. 'GO:0000150' has a similar comment explaining the absence of the relationship, so I haven't added it in.
- need children that are site-specific and not site-specific; then grandchildren are tyrosine, serine or DDE based
- How do excisionase and invertase and integrase fit into DNA cleavage activities or are they separate?
- Becky will do process:function relationships for these
DONE. Added P/F relationships as follows:
DNA integration ; GO:0015074 --[part_of]integrase activity ; GO:0008907
DNA recombination ; GO:0006310 --[part_of]recombinase activity ; GO:0000150
BUT... the GOEds need to look at the cellular parentage of the DNA metabolism terms. Causes disjoint TPVs when a protein metabolises the DNA of another organism. Several of the definitions & synonyms of child terms will be affected.
- Should we include the complexes transpososome, intasome, resolvasome, relaxasome?
done. BM will send tomorrow.
- How do we describe the injected proteins?
- not in scope of GO directly
- functions possible -- RNA binding involved in genome entry into host cell
- what are the types of proteins?? BM will find out.
- What should the definition of terminase activity be? Is it necessary?
done. BM will send tomorrow.
- Need to redefine GO:0046797, GO:0019061 & GO:0004803.
- Is GO:0098034 ok?
- What do we do with the plasmid virus terms?
- new terms by Jane suit these fine
- What do we do with replication by transposition terms?
- has part transposition, DNA-mediated (GO:0006313)
- under viral genome replication (BM)
- How do we handle the viral envelopes since some are INTERNAL, others are EXTERNAL, but the current defn is only for EXTERNAL?
- merge virion membrane and viral envelope & make children for internal and external
HELD OFF on the merge because I see viral membranes crop up again for our Thursday session.
- What do we do with GO:0009293 (transduction) and children from BM?
- toss it. obsolete.
Spanins and Holins
- Do we want the children of spanin terms? At the least, the defn for spanin in MeGO needs to be altered.
- process term for spanin under disruption by symbiont of host cell (GO:0044004) - Jane
DONE (Jane). Added 'cytolysis by virus of host cell ; GO:0044659' and 'disruption by virus of host cell membrane ; GO:0044662'
- Function is difficult, but Becky has bravely volunteered to look at the spanin & holin activities
- maybe GO:0052025
Background to what holins do:
- essential for host lysis by bacteriophage.
- small membrane proteins
- accumulate in membrane then act to permeabilize the membrane (by making themselves into a hole). Permealized either to an endolysin, so the endolysin can reach the cell wall and degrade it (thus the holin controls the functional access of the endolysin to the murein) or to ions to cause a collapse of the membrane potential.
- Doesn't appear to be known if the hole is just a hole, or an actual channel.
- Holins act as 'clocks' and only make the holes when the time is right. Not sure how this is judged yet.
- If the holins are not considered to be channels (see question below), there's no suitable function term, short of 'hole activity'. Therefore, I propose to obsolete the existing 'holin activity' terms, and replace them with new process terms. We've tried obsoleting 'holin' twice before, but it's still managed to stay in the ontology with 'activity' bunged on the end... sneaky. Here's my suggestion... let me know if it works for you:
obsolete: holin activity ; GO:0034290 canonical holin activity ; GO:0034291 pinholin activity ; GO:0034292 Reason for obsoletion: These terms represent a family of proteins and not an activity. Replacement terms are suggested below.
Add new terms: regulation of plasma membrane permeability ; GO:NEW1 negative regulation of plasma membrane permeability ; GO:NEW2 positive regulation of plasma membrane permeability ; GO:NEW3 plasma membrane permeabilization involved in cytolysis by virus of host cells ; GO:NEW4 plasma membrane permeabilization to endolysin involved in cytolysis by virus of host cells ; GO:NEW5 plasma membrane permeabilization to ions involved in cytolysis by virus of host cells ; GO:NEW6
Definitions of new terms:
regulation of plasma membrane permeability ; GO:NEW1 Any process that modulates the frequency, rate or extent of the passage or uptake of molecules by a plasma membrane. is_a: regulation of biological quality ; GO:0065008 is_a: plasma membrane organization ; GO:0007009 (Similar for negative and positive children)
plasma membrane permeabilization involved in cytolysis by virus of host cells ; GO:NEW4 synonym: holin-mediated permeabilization [EXACT?] synonym: holin-dependent membrane permeabilization [EXACT?] synonym: positive regulation of plasma membrane permeability involved in cytolysis by symbiont of host cells [EXACT] synonym: cytoplasmic hole formation during host lysis by bacteriophage [NARROW? or EXACT?] synonym: holin activity [RELATED] The temporally-regulated permeabilization of the host plasma membrane (cytoplasmic membrane) by a virus/bacteriophage during lysis of the host cell. Comment: The transmembrane holin proteins accumulate in the membrane of the host cell, and at a specific time point form a hole through the cytoplasmic membrane that allows the passage of enzymes and/or other molecules to lyse the host cell.
plasma membrane permeabilization to endolysin involved in cytolysis by virus of host cells ; GO:NEW5 The temporally-regulated permeabilization of the plasma membrane (cytoplasmic membrane) to a fully-folded phage-encoded endolysin (murein-degradase), so the endolysin can reach and degrade the murein within the cell wall during lysis of the host cell by a virus. exact synonym: endolysin-specific hole formation during host cell lysis by bacteriophage synonym: canonical holin activity [RELATED] plasma membrane permeabilization to ions involved in cytolysis by virus of host cells ; GO:NEW6 The temporally-regulated permeabilization of the plasma membrane (cytoplasmic membrane) to ions, causing irreversible depolarization of the cell membrane and lysis of the host cell by a virus [PMID 19861547]. synonym: hole formation during host cell lysis by bacteriophage [EXACT?] synonym: pinholin activity [RELATED]
QUESTIONS ON HOLIN TERMS:
- QUESTION 1: membrane organization is under 'cellular process'… this is going to cause problems again, isn't it.
- QUESTION 2: wrt whether the synonyms should be exact or narrow, would you use these terms to annotate anything other than holins?
- QUESTION 3: wrt definitions & synonyms, is this process specific to bacteriophages?
- QUESTION 4: Am I right in saying that it's the plasma membrane (equivalent to the cytoplasmic/inner membrane in bacteria) that the holes are formed in?
- QUESTION 5: Would you say that a holin should be annotated to 'channel activity'?
Background to what spanins do (PMID 20734329):
- Acts at the 3rd step in lysis (acting after holins and endolysins): involved in disrupting the outer membrane (OM).
- span the periplasm
- form dimers and monomers
Add new terms: disruption by virus of host cell outer membrane ; GO:NEW disruption by virus of host cell outer membrane involved in cytolysis by virus of host cells ; GO:NEW
New term definitions: disruption by virus of host cell outer membrane ; GO:NEW A process by which a virus has a negative effect on the functioning of the host's cell outer membrane. The cell outer membrane is a lipid bilayer that forms the outermost layer of the cell envelope.
disruption by virus of host cell outer membrane involved in cytolysis by virus of host cells ; GO:NEW A process by which a virus has a negative effect on the functioning of the host's cell outer membrane that contributes to lysis of the host cell. synonym: spanin activity [RELATED] synonym: OM disruption during cell lysis [PMID: 20734329] comment: Consider also annotating to 'host cell periplasmic space ; GO:0044229'
QUESTIONS ON SPANIN TERMS:
- QUESTION: Do you know HOW the spanins disrupt the outer membrane? Is it just by being wedged in the periplasmic space? Might be by fusing the OM with the plasma membrane (PMID 20080651)
- GO:0019038 - obsolete.
- GO:0033061 - need child term examples (i.e. RecBCD is a ??? complex)
- Becky will expand definition to clarify prokaryotic
IN PROGRESS... DNA recombinase mediator complex ; GO:0033061 is_a nuclear part, which currently restricts its use to Eukaryotes. If we expand the definition to include bacteria, this parentage will need to go, but it will most likely need to be added to all the current yeasty child terms.
- GO:0060144 - needs to be under multi-organism process
DONE (Jane). Fixed immediate parentage issue. Although virus-induced gene silencing is something that really needs looking at in more detail - the terms we have are really outdated with recent developments - RNAi etc. And in fact virus-induced gene silencing is now only ever mentioned as a technology rather than a biological process, so these terms are extra confusing. I'll make a SF ticket.
- create term cytolysis by virus of host cell
DONE (Jane). See above.
- GO:0045090 - obsolete.
- genome types (DNA, RNA) in cellular component tree
- capsid self-assembly term
- under viral capsid assembly