20th GO Consortium Meeting Minutes

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Ontology content development

Overview (Midori)

Most of the report is on the wiki. A lot has been accomplished. Highlights include the following:

  • closed more SF items them opened since last meeting (~200)
  • peptidase reorg is finished: After SLC meeting, MEROPS database curators were contacted and they made recommendataions. Those recs have been acted upon and reorg is finished.

There still are ~200 open items. All those that are more than 6 months old have been assigned but maybe those should be reviewed to see if the priority should be changed. Also, David mentioned that many of the items are being taken care of the in large chunks with ontology changes, such as "biogenesis and organization" terms. Some are stuck because no consensus can be reached.

The majority of the ontology content section will talk about future work and the links that will be made between function and process ontologies.


(everybody) SF items that cannot be closed due to lack of consensus should be put onto a wiki page so they can be resolved at an upcoming GOC meeting.  Midori said to email the editors and they'll take care of it.

Theory and examples of function and process links (Harold, Jen)

(get his slides)

Many groups have been working on systems for links trying to see how it works since it does represent biology. Harold showed examples of cross-products using biochemical pathways, defining a start and end, selecting paths, and using common resources. Done manually, the links looked OK but labor intensive. Could it be done automatically?

Problems with doing it automatically:

  • missing DBXREFs
  • too many DBXREFs
  • creates links in the ontology that are "corret", but not always helpful to a given question for a human - like BP "carbohydrate metabolism"is linked to all glycolysis MF annotations.

Moving forward, using the dbxrefs seems to be the way to go but we will have to go in manually to make them more complete.

(from chris' and Jen's talk)

So why should we even bother?

  • It will improve the GO because we need to be specific
  • It will help fill in annotation gaps - such as a MF "kinase activity" should be made to the BP "phoshorylation" - as well as provide ways to make suggestions new annotations.
  • It will allow better integration of pathway databases with GO.

Chris has been try to use Reactome to make mappings between function and process and has come across the following issues:

  • DBXREFs not necessarily equivalent
  • There are some reactions that always occur in a given process for a particular species and others that do not and this is more difficult to mine from reactome.

There are also gotchas from biology because there could be multiple variations for lysine biosynthesis that include mix-and-match reactions and variations of those reactions. A combinatorial explosion.

The proposal to deal with this:

  • When functions and process are closely related, like kinase and phosphorylation, can make a "part_of" annotation.
  • new relationship "sometimes part_of" when automated mappings are brought in which will avoid true path violations.

Function and process link discussion

David asked if every function should be a "part_of" process? In theory, there should be a link between each Molecular Function term to a Biological Process term. And there was general acceptance of this theory.

Eurie asked if MF enzyme terms made consistently in order to best make the links easy/consistent? Amelia pointed out there is also another issue that enzyme terms are usually forward and backward but we need separate terms. Harold also pointed out that we copied from EC but this may mean that two GO terms may exist solely on the basis of cofactors. So all these may contribute to issues in creating an automated mapping.

Suzi and Peter discussed that the definition of pathways between Go and Reactome are different, using apoptosis as an example. There are good examples where start and end may be different from organisms to an organism. Ingrid mentioned John Ingram (an experienced physiologist) said a metabolic pathway should begin and end with a central metabolite. Then pathways can feed into a common point that can then go to a central metabolite. But there is probably less consensus for models that are still being developed. All agree that a discussion needs to occur to work on coming to a common agreement.

Paul pointed out there we were discussing two extremes: an uncurated automated link and curated links. The curated links are the ultimate goal but there could be a compromise in the middle. The relationship linked between MF and BP go through KEGG, that evidence trail is documented. This is something better than "sometimes part_of". The concern with this is that changes other groups make need to be propagated.

There was a discussion about the impact on curation. With these inter-ontology links, you have to take the links in account as a true path rule. In addition, how much evidence do you need to make those annotations? That is why there is the "sometimes_part_of" but what if that pathway doesn't exist in your organism?


* Add obvious part_of links, like MF "kinase" and BP "phosphorylation"; will be rolled out after regulates is released in Feb 2009
* The sometimes_is_part relationship was agreed as a good idea. We should try mining pathways for sometimes_part_of relationships using glycolysis, nucleotide metabolism, apoptosis first
* Agree on beginnings, middles, and ends of pathways/processes between Reactome and GO
* Examine impact on annotation priorities and implememntations
* Can we source our relationships as well as our term definitions.
** (david: this is about pushing the work onto the ontology developers and not the annotators) 
* assign process to every molecular function.
* deferred: co-annotation 'has function as part of this process'

New relationship type (David)

New relationships will be released to the public in Feb 2009. This is the first cross-ontology links between BP and MF. It will occur between the BP "regulation of catalytic activity" and MF "catalytic activity". Those functions that regulate function terms will get the regulates relationship.

One major consequence is that all groups have to take into account relationships. The BP "negative regulation of kinase activity" is part_of "kinase activity", but the slimming will make them "kinase activity". Need to be careful about this.

Michael was concerned about whether the meaning of "part_of" was being overloaded. David replied that we probably are but practically, it may not matter because the child term really cannot be part of the both parents at the same time.

We will have to make sure that GO tools support these links. In addition, we need to make sure that users who develop tools are aware of these changes. Jane emphasized that we couldn't do testing for all tools but the users need to test.


(tanya) Send out function process email again.
(chris) Release examples of relationship usage for software development.

Quality Control (Tanya)

Much of the information is on the wiki. For regulation terms, the reasoner looks at regulation terms and then at corresponding process terms, checks if the structures match or if relationships missing. These were all reviewed.

Ontology developers will continue to review Chris' reports - it's becoming part of the process of ontology development since it is part of OBO-edit.

OBO-Edit (Amina)

(has slides)

Priority should be testing and bug fixes. This version doesn't need more features but all the new features need to be tested, tested, tested.

Reports (Jane)

(has slides)


This is an ongoing process. Lots of "regulates" terms.

Organization and biogenesis of cellular components

(has slides)

All "organization & biogeneis" terms will be changed to "organization" with the proposed high level structure:

-[i] assembly
-[i] disassembly
-[i] maintenance
-[i] morphogensis
-[p] assembly
-[p] part biosynthesis


(ontology dev) Continue work on "organization and biogenesis" terms.  Maybe biogenesis & organization should be switched at the higher level but this is up for discussion.

Signaling (Jen)

(has slides)

Is responding to the signal the same to the reception of the signal? Currently defined as within the realm of reception of the signal?

Future content meeting discussion

The discussion of signaling touches on every species. David pointed that some of these are huge issues - signaling alone can be roughly categorized into

  • g-protein coupled receptor signaling
  • calcium signaling
  • tyrosine kinase singaling
  • MAP kinase cascade


Pursue an ontology development meeting one or two:
   (Brenley, Kimberley, Candice, Michelle, Jane) Viral processes
   (Pascale, David, ???) GPCR
(?) A couple of GO meeting with major meetings on these topics
(?) Investigate funding sources

Annotation checking by trigger file (Jen)

(has slides)

Of 47,000 errors in the GOA file (0.14% of total), only 5 manual annotations were flagged suggesting that the graph may need improvement. The rest were IEAs.

Trigger file is being used by GOA and MGI for consistency. There was discussion whether this use should be expanded and run against all annotations when the files are submitted. This would address a QC aspect.

Emily said that it can be used as feedback to InterProt (for the InterProt to GO mappings) to update mappings because old mappings are causing problems. Dan also suggested that it could be integrated into QuickGO as a public resource.


(?) remove sensu synonyms
(Jen) Continue implementation of trigger system
(Dan) Make GOA quickgo checking available to the public
(?) write up for near future news letter

General Annotation Issues

Evidence code ontology (ECO) (Michelle)

Michelle is taking over managing the Evidence Code Ontology.


  • Correct incosistencies in the ECO with GO
    • ECO exists as its own and includes things other than GO and GO pulls from the ECO, using a subset

Mike asked is ECO the responsibility of this community? Michael says yes because we started it. We have not used it because we wanted to start out pretty easy. TAIR then wanted a much richer set of evidence codes. Michael and Sue did a mapping. But when TAIR reports to GO, they collapse the evidence codes down. Those arguments are still valid. If curators were faced with more evidence codes, it would take longer. IDA could be expanded to a zillion codes.

Michael thought we should integrate GO evidence codes into the ECO because other people might use them and that GO should use a subset/slim of ECO (i.e. the ones that we are using the ones we use now.) Judy agreed and said if an individual MOD wants to make use of the granular codes, they can, but they must be mapped up to the higher-level codes used by the GO.

Pascale asked if we needed to use the the more granular terms adopted by GO (ISM, ISO, ISA) or if we could keep to the higher level terms. This was deemed fine--Suzi pointed out you should annotate to the degree of knowledge available and this might end up being to the more general EV code. Also this allows for not having to retrofit older annotations as brought up by Harold.

Suzi brought up there could be various slim sets for various projects - AmiGO, Ref Genome, etc. for display purposes in the interfaces.

In response to a question from Eurie, it was stated that the GOC would only set standards for the GOC accepted codes, not all codes. Each database could have use more if they wanted, but would have to convert it into the standard set for the GA file.

Maybe EXP would be better when there is no consensus on which evidence code should be made. This may prevent spinning it. For use of ref genome, maybe have to have additional standards available. There were concerns from Peter about overloading the EXP term and/or losing accuracy. There is a lot of time spent debating which lower code to use and Rex would rather have people agree to EXP and spend more time annotating.

Any evidence code that is in the ECO could be submitted to the GOC for adoption. We could also explore writing software to slim the evidence codes used.


  • We will use the ECO and create an EV code ontology tracker (Suzi)
  • people can use the ECO in its entirety but they have to map up to the GO set of EV codes.

Separating annotation method from experimental method

In principle, most everyone was supportive of the idea to separate the evidence used to make the annotation and the curation method to make that annotation. There was, however, much discussion on the scope and implementation of this proposal.

Two implementation methods were proposed:

  1. A new column that contains a text describing the annotation process
  2. Creating a cross-product between the evidence code branch of the ECO and a methods branch of the ECO. This ID would be used in the GAF.

Because proposal 2 does not create a new column and is expandable to multiple combinations, it was favored.

Proposed methods were not agreed upon but words that were used to describe included

  • curator reviewed
  • not curator reviewed
  • electronic
  • manual

A direct consequence of this would be that IEA would go away. Emily proposed the following mappings:

  • Interpro2GO -> ISS/ISM, not reviewed
  • keyword mappings -> TAS, not reviewed

IEAs are stripped out after a year. How would those "not curator reviewed' be treated? Since the intent was to remove annotations based on sequences, maybe only those should be removed because they can be easily recomputed. Large-scale/high-volume/high-throughput experiments won't be repeated but still are experimental. We would have to consider exceptions for these.

There was some discussion about what users wanted and how users were taking advantage of the evidence codes. There is a range - some people just strip evidence codes and do not consider them. However, others would take advantage of additional levels of information. Both advisors mentioned that what users wanted was a level of confidence. This, however, would be difficult to do.

It was agreed that multiple issues need to be considered when dealing with this new qualifier of evidence codes:

  1. the experimental evidence
  2. was there judgement involved
  3. was there a review of the data


(Suzi, Michelle, Judy, Pascale, Emily, Eurie) Example cases of annotations and implementation into the ECO

PAMGO (Michelle/Candace)

Candance gives an overview of the new terms. Project is coming to an end - funding is coming to an end. New gene association files have been submitted.


  • PAMGO terms outside of PAMGO: viruses, c. albicans, p. falciparum, t. cruzi, t.brucei.


  • incorrect uses also.
  • there are a few terms where it is ambiguous whether or not the process is for the host or the virus side.

Future directions

  • fix virus terms
  • add comments
  • adopt more descriptive form for annotations.


  • missing taxon ids for dual taxons
  • need a way to capture "acted_upon" annotations

Dual taxon IDs

  • still not displayed in AmiGO due to technical issues


  • Check your annotations to terms under the 'symbiosis' and 'interaction with host' branches to make sure that there aren't any problems.

Cross products: Column 16 (Tanya)

Initially proposed in Jan 2007.

Reminder: this is extra information to combine multiple terms in a single annotation. These are GOIDs that we don't want to encode links in the ontology. If there is more than 1 localization, they can be piped and several different ontologies can be piped in the same row.

  • You are not restricted to one ontology in column 16
  • Column 16 is optional
  • Column 16 can also be used to identify a target i.e. regulation of transcription (Note that the current documentation states that column 16 is only for external ontologies.) or a chebi ID for a chemical when annotating "response to drug".

There were two proposed solutions on the table:

  • simple solution
  • expressive solution

No one had concerns about adding this column and a few people spoke up in favor of the expressive because it would allow for more information and no need to retrofit.


  • go ahead with the implementation of the expressive model in column 16
    • get more examples
    • get the documentation together

Transitive Relationships in GO

(has slides)

Relationships in terms, it's wrong to just slim terms given the different relationship types. Unless you're careful, you will violate true path rules.

  • The composition of is_a and part_of need to be taken into consideration for true path violations.
  • If you regulate a process, you regulate part of that process, not that whole process.
  • As you add more relationships, you need to create these transitive closures.
  • And as you take these into consideration, the slimming can become more sophisticated.

Judy proposed that we need a tool to help with this.

Day 2

Paul: how curators can use evo trees

(has slides)

  • Discussion of current process
  • New process
    • will now build trees using MOD data
    • these tree will be used to make annotations concurrently and consistantly with evo tree
  • Short-term solution has been implemented
    • some cutting and pasting done--a little ad hoc
  • What about the long term?
    • several ideas
  • update on progress with gene trees and homolset selection tool
    • getting there
    • far enought that it has worked on an end user machine
  • better definition than ortholog
    • equivalogs
    • genes most similar to common ancestor
  • Example: NEDD4
    • tool shown
    • judy: what info did you use?
      • ensembl...
  • annotation inference based on homology
    • must be correct and consistant
      • experimental evidence
      • evolutionary correct paradigm
      • traceable evidence trail
    • example... ubiquitin-protein ligase activity
      • judy: showing just terminal nodes in GO tree? or going up the tree?
        • actually, going up the tree
        • will be able to put bootstrap values on the tree
  • tree gives us an explicit model for the evolution of gene func/proc
    • this allows consistent inferences
  • judy: long term plan is updating trees regularly and combine into AmiGO and look at how distributed in graph
    • will be able to see alll of the data at the same time to seem where you can and can't transfer information
    • interprot will make sure that all of the information we need is in there

Kara: the annotation process

(has slides)

  • big picture (this is an iterative process)
    • have a new protein family curator that suggest protein based on tree
    • MOD annotate all experimental data to completion
    • protein curator mediates annotation review
  • mike: how do you envision interaction between mods
    • social; will talk more about it
  • rex: we need a fixed time scale to make sure that we get results
  • generating reports to help get outliers and other oddities
  • mike: are there equivalog sets that will be excluded?
    • [general discussion]
  • candace: will tree include bateria?
    • it does, it will
    • horizontal x-fer makes things hard
  • mike:
    • [general discussion]
  • judy: looking at GO next to trees would be neat
  • m.a.: what happens when the tree changes?
    • small changes in group won't matter
    • real question is if the common ancestor changes
  • princeton / p-pod update
    • search
    • spec dist graph
    • new algorithm (notom(?) from MIT)
    • interactive applet
    • if you have suggestions, please sent them along


Suzi: Discussion

(has slides)

  • uniprot; complete proteome project
  • protein curator; how to efficiently incorporate input from all MODs
  • how to deliver resulting homol-based annotations to MODs
  • judy: doesn't like gp to protein files
    • what's in a name
  • judy: MODs are building gp to protein, how to work with uniprot?
    • judy: eventually they will be working together


GO contacts uniprot to sync (mouse rat chicken zfish)
  • kimberly: want reference protein with all the exons?
    • yes


Generate definition for what each of the files needs to be and generate tags (paul and kara)

  • judy: multiple reps of protein families, want to take advantage of them, like swissprot
    • completely extensible, can put in as many as you want
  • need to be careful with definitions, maybe we should be better
  • m.a.: we should go slow and prepare a document for this and make sure that we have everybody with us
    • we aren't in a hurry


paul and Kara draft and m.a. will take pass afterwards

Suzi: Mor Discussion

(has slides)

  • let's talk about the flow
    • should we do it as in the slides?
      • no complaints
  • paul: should we try this as part of electronic jamboree? we can try and time it
    • judy: a set of genes in a month
    • pascale: want to change how we do it
    • judy: how are we selecting genes ...?
      • suzi: we use the trees
        • judy: hat selection is dependent on exp anno
    • paul: we wont use current anno to select genes
    • pascale: disease genes, no anno, highly conserved
      • some might be easier (pascale's display)
    • judy: are we going to contine with what we're doing?
      • rotation, etc.
    • pascale: pascale and kara will define the set
      • judy: set the priority sets
        • rex: let's just move forward
    • judy: can we do this next week?
      • yes


pascale will provide list at the beginning of each month

  • suzi: give a gene/focal point, what from every species is the protein that you want to include--that will be the tree stuff
  • suzi: no discussion about the seed; but we may have one about the set.
  • rex: let's just truct paul's trees, good enough
  • kara: will have much improvement once we start using trees
  • pascale: any problems should bump back to paul and kara, not necessary to discuss as a group
  • debbie: more fruitful to have calll just about inference set after jamboree
  • kara: want to just hammer things out with pascale and have a concrete system
  • judy: MODs should incorporate new inf instead of GO
    • rex: as req of being part of RG, need to add infs quickly
    • m.a.:
      • judy: wary of paralog groups
        • paul: that's what we're doing
          • crosstalk
        • paul: MODs should check tree, until comfortable
      • paul: how does PF interface with mods?
        • david: not conference, but one-on-one would be better
          • rex: have them review, and if they have a problem, the onus is on them
      • suzi: (on diagram)
        • pascale gives example with diagram
    • m.a.: need to be in MOD and GO db; what is route?
      • paul: we can put the non-MOD inferences in GOA?
        • yes


pascale picks gene by magic


set done by kara and paul, complaints to them

  • trees done every six months


one-on-one MOD discussion (if problem)

  • mechanics of how this all gets into MOD and GO db
    • suzi: possibilites:
      • opt 1: if it goes back to MODs from PF DB
        • there may be a delay
        • rex: timelime agreement could solve it
      • opt 2: done in DB load script
      • rex: likes first; if we need police, so be it; opt 2 not good--mods shouls control their own data
        • judy: agrees
      • pascale: like opt 2
        • crosstalk
      • david: opt 1
        • nervous about sync delays
      • eurie: likes opt 1
      • emily: opt 1


option 1
  • judy: what is evcode, what is source?
  • judy: this will make versioning easier
  • rex: ref gen as source
    • increase visability--branding!
    • in twice yearly tree change, how big are they usually?
      • paul: not too likely; and an auditable process
      • pascale: let's say we have 5% of 10000 trees change, can we identify them?
        • paul: since we;re just interested in local properties, not a big deal
        • pascale: if there is new info in mouse for that tree ...
          • need to make sure that annotations are current
  • suzi: evcode discussion should wait until we have something to discuss
  • everybody has warm fuzzies about the PF/RG developments

Mike: Annotation Progress

(has slides)

  • folks like these graphs
    • shows sept 07
    • shows may 08
      • chickens added
      • not a lot of change
    • shows graph from a couple of days ago
      • progress is clear
  • judy: uniprot has done human proteome, number are different
  • paul: has number on FTP site
  • RG graphs
    • sept 07
    • april 08
      • number changed with
    • most recent
      • everything decreased except human
        • i can update if I get these in the next few hours
    • suzi: in proposal, we can use your software and automate it


(berkeley) automate mike's graph (as in proposal), need to be able to see progress through time

David: RG from ont dev prespective

(has slides)

  • we work through SF
    • RG request are prioritized
      • two flavors
        • new term for RG
        • problem areas in ont
          • slower
  • need annotors to get info about "response to" terms
  • doing signalling now
  • ...argh...
  • please use SF and mark as RG
  • pascale: documentation and anno consis
    • when doing big branch of ont, more discussion with RG group
  • jen: doc for every big reorg, sometimes I don't know about a change
  • debbie: def is sometimes unclear
    • ex: ATP binding
    • pascale: "binding", "regulating", ev--these are always a problem
    • pascale: we need a group to make a proposal to get the defs down flat
    • peter: ont distinguishes binding from catalysis
    • kimberly: we're not consistant about how we use binding
    • rex: documentation is the core issue
      • docs will solve all of the above


come up with rational plan for documentation and indexing (including rational and examples)
  • suzi: we can ask the SAB about this as well
  • ingrid: i look at term def
  • how should we do this?
  • seth: why not GONuts and not muck-up the data
  • richard: examples would be very valuable, including counter examples
  • pascale: add more fields that didfferent people could see
  • alex: users should see the information
  • jen: wants one single information resource
  • mike: this curator info shouldn't be private--this is good stuff
  • debbie: seconds mike, and GONuts
  • emily: seconds
    • children as well
  • jen: graph can be weird
    • david: will fill in missing bits
  • jane: docs go bad over time need freshness
  • david: great defs vs. curator judgement--still an art
    • harold: seconds; always constrained by training




Look at action items from last meeting

  • push forward not dones
  • carry forward documentations issues

Previous Incomplete Action Items

Status Responsible Party Task Comments
In Progress Documentation working group Document annotation SOPs Another factor we have been tracking is when a curator judges that the curation of a gene is ‘comprehensive’, that is, that is accurately represents the biology (irrespective of the number of papers available or read). This appears in the spreadsheets. The guideline is that when there are few papers, all papers should be read; when there are many (a curator can judge what is too many), then a review should be read to find the important primary literature and decide what information needs to be captured. We don’t keep track of whether or not reviews have been read. Wormbase uses textpresso (PMID 15383839), that helps ensuring curators do not overlook information. The ‘comprehensive’ curation status doesn’t get invalidated when a newer paper is published; however, curators may (and are encouraged to) update the date when the newer literature is curated.
Chris Mungall Re-calculate with is_a only paths
Chris Mungall Re-calculate with experimental codes only generate several versions of the data classified by different evidence codes?
Chris Mungall Provide such reports on a regular basis
Judy Blake Contact NCBI/NLM/OMIM to link to reference genome genes
In progress Documentation working group Document Changes to Gene Association File (GAF) column 2 is canonical gene ID; column 17 is thing you are annotating (always required); column 12 matches column 17 and contains SO ID's; add header to gene association file
In progress Documentation working group Document Changes to gp2protein file includes complete gene index (except for pseudogenes and transposons); column 1 is canonical gene ID; column 2 is accession for sequence of longest form of protein from UniProtKB: or NCBI; syntax of gp2protein file will be provided by Mike and Chris
In progress (Jane) write notice of changes to GAF and gp2protein to users
In progress MODs + Ben Hitz make sure that their input matches new GAF and gp2protein requirements
Seth Carbon Have AmiGO show co-occurrency terms similar to function in QuickGO.
Seth Carbon & Val Wood SLIM by SLIM matrix Would be used to review intersections of different cellular processes and look for unexpected intersections which may identify possible errors. Try first applying to function and component terms; outline cells that you expect to be empty, Have these matrices generated automatically from the AmiGO database.
Ben & Mike Get isoforms into GO database
MODs & Chris Consistent use of IMP "with" column Chris will be talking to individual groups with how they use the with column for IMP. Each MOD groups needs to respond to this for Chris.
Michelle Implement Michelle's proposal decide whether to put 'response to drug' ID in column 16 or is separate IC annotation. Annotate to chemical term ‘response to cocaine’, co-annotate with chemical term for now, then later when available, put GO ID for “response to drug’ in column 16 (or separate IC annotation).
pending Midori, David, Chris, Mike Bada Chemical derivatives and metabolism terms Need input from Chris and Mike on how much can be automated; possibly also current and near-future state of ChEBI
MODs & Pascale All groups to check on how they use IGI and update annotations as per Princeton discussion.
Val Circulate draft doc on how contributes_to can & can't be used Will include: "Would this annotation make sense if this subunit was" ... [thought not finished; might be something like "viewed by itself"].
MODs & Pascale Check existing annotations for "contributes_to" with IDA We think only allow contributes_to with IDA. Look into adding to annotation checking script to flag contributes_to.
Jen Implement rules and software for sanity checking automated annotations (species-based trigger file).

New Items

Status Responsible Party Task Comments
empty empty empty empty