Difference between revisions of "20th GO Consortium Meeting Minutes"

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(ACTION ITEM)
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== Michelle: Evidence code ontology (ECO) ==
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== Evidence code ontology (ECO) (Michelle) ==
 
Michelle is taking over managing the Evidence Code Ontology.
 
Michelle is taking over managing the Evidence Code Ontology.
  

Revision as of 14:00, 21 October 2008

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.

ACTION ITEMS

  • 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?

ACTION ITEMS

  • Add obvious part_of links, like MF "kinase" and BP "phosphorylation"; will be rolled out after regulates is released in Feb 2009
  • 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.

ACTION ITEM

  • Send out function process email again.
  • 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)

PAMGO

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:

biogenesis
	organization
		biosynthesis/formation
		assembly
		modification/processing
	disassembly
		catabolism
maintenance

ACTION ITEM

  • 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

ACTION ITEMS

  • Pursue an ontology development meeting one or two
    • Viral processes (Brenley, Kimberley, Candice, Michelle, Jane)
    • GPCR (Pascale, David, ??)
  • Couple a 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.

ACTION ITEMS

  • remove sensu synonyms
  • 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.

Goals:

  • 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.

ACTION ITEMS

  • 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.

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

ACTION ITEM

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

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.

Successes

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

Issues

  • 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.

Fixes

  • 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

ACTION ITEM

  • 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.

ACTION ITEM

  • 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.

Look at action items from last meeting

  • push forward not dones
  • carry forward documentations issues