These are some notes I typed up after the Nov. 2000 meeting. I've
deposited them as a supplement to Courtland Yockey's notes.

midori



Minutes of Gene Ontology Consortium Meeting
4-5-6 November 2000  (Berkeley 2000 Meeting)

Table of Contents

Table of Contents	1
Groups represented	2
Process Ontology Discussion	3
Embracing the Explosion	3
Sensu to the rescue	4
Anatomical Lexicons and GO	5
Granularity and the Purpose of the GO	6
Distinction between GO and Partner Databases	6
Progress Report - General	7
What is the GO NOT	7
A couple of brief notes	7
Mapping GO to other Lexicons	8
Human Annotation	8
Evidence Codes & Documentation (Midori)	11
...and what every happened to Proteome	11
Progress Report - Flybase  (Michael Ashburner & Heather Butler)	12
Progress Report - SGD  (Midori Harris, Mike Cherry)	13
Progress Report - MGI (David Hill)	14
Progress Report - TAIR (Leonore Reiser)	15
Progress Report - Wormbase (Erich Schwarz)	16
Progress Report - Prokaryotes & Protozoa	17
Software Developments	19
Java Browser (John Richter)	19
Java Editor (John Richter)	19
Technical Discussion : aiming for a Generic Ontology Builder	20
HTML Browser (Brad Marshall)	20
BLAST Server (Suzanna Lewis)	21
Timing, Resource, and Prioritization Issues	21
Interim Solution during resource-limited period	22
Downloads from the 'outside'	22
Discussion around the Editing Process	24
Schema Discussion, with emphasis on DBxREF	25
GO SLIM	27
Utility of GO SLIM	27
Status of GO SLIM	27
Funding	29
Publications	29
Next Meeting	29
Appendix A:  Current GO SLIM	30

In attendance (complete list with little disinction for partial attendance)
Michael Ashburner (Flybase)
Suzanna Lewis (Fly)
Mike Cherry (yeast)
Heather Butler (fly)
Midori Harris (yeast)
Sue Rhee (arabidopsis)
J. Yoon (arabidopsis)
Leonore Reiser (arabidopsis)
Chris Mungall (fly)
Courtland Yockey (AstraZeneca)
Judy Blake (mouse)
Brad Marshall (fly)
David Hill (mouse)
Selina Dwight (yeast) (arrived afternoon 5 Nov)
Erich Schwarz (worm)
Cathy Ball (yeast)
Gavin Sherlock (yeast)
Kara Dolinski (yeast)
John Matese (yeast)
John Richter (fly)
Lukas Müller (arabidopsis)
  Groups represented
 Drosophila - Flybase
 Yeast - SGD
 Mouse - MGI
 Arabidopsis - TAIR
 C. elegans - Wormbase
 Pharma - AstraZeneca
  Minutes authored by Judy Blake and Courtland Yockey
  Minutes edited by Midori Harris
 
 Note ... items under 'clearinghouse' topics are incorporated into 
Progress Reports
 

 Process Ontology Discussion
 
 From before the meeting actually started through to the end of the 
first day, discussion kept ranging back to the Process Ontology.  By 
9AM, Michael and Judy were discussing how the term 'heart 
development' might be exist in both GO and MGI DAGs, but that they 
would mean different things.  By the end of the day, it appeared that a 
consensus had been reached whereby 'heart development (sensu 
Mammalia)' in GO might be a conceptual equivalent to what MGI and 
its users might need under the heading 'heart development.'  
Needless to say, much additional discussion need follow this, but there 
was a definite feeling that progress was made in tackling the 'anatomy 
of process' problem (my term, not introduced at the meeting).  It 
appeared that this was very much a fly/mouse oriented discussion, 
that the granularity around the worm and plant and fungal anatomical 
issues were not deeply addressed.  That being said, the 'solution' 
arrived at was to 'embrace the explosion' in such a manner that any 
organism might be handled.  It also appeared that addressing mouse 
anatomy was a generally accepted surrogate for mammals in general, 
as a first pass.
 
  Embracing the Explosion
 
 What does it mean to include anatomy?  Better yet, what happens if 
you do not include it, or include it 'incorrectly'?  It was thought at one 
time that anatomy could indeed be excluded from the GO, but this 
runs into a number of problems, chief among them being that anyone 
looking at a Process Ontology might well expect to see terms such as 
'spermatogenesis' or 'heart development'.  In the absence of such 
'important' and pervasive terms, the utility of the GO is significantly 
diminished.
 
 One possible solution discussed at length and eventually abandoned 
was that of combinatorial terms.  Such Combi-Terms (my phrase, not 
used at the meeting) would take components from existing ontologies, 
creating a new term that does not exist in either, effectively creating a 
term set that is not itself hierarchical but bridges two hierarchies, 
thereby allowing entry and tracing of each one touched.  For example, 
the notion of encoding the concept 'heart development' as 'heart 
(anatomical ontology)' + 'development (process ontology)' was 
discussed.  In such a situation, a term could be either a literal (an 
explicit part of one of the ontologies) or a symbol combination (a 
combination of literals, a Combi-Term).  The combination inherits the 
lexicon and the hierarchical position of each component term, but not 
the definitions of the components; a definition and GO ID would be 
assigned to the Combi-Term.  However, this solution is prone to drift-
error, meaning that the Combi-Terms might not keep up with changes 
in the anatomical and process ontologies.  Further, there are problems 
inherent in using only symbols and divorcing those from the meanings 
of the symbols while retaining their hierarchy positional information, 
chief among these being suspicious hierarchy tracing.  For instance, 
given 'heart development' applied to a fly, there is no constraint 
preventing hierarchy tracing to 'heart valve development,' which is 
inherently non-sensical for the fly.
 
  Sensu to the rescue
 
 The solution that seemed communally acceptable was to invoke the 
existing 'sensu' notation.  In the case of 'heart development,' the 
sub-graph might look like:
 
 	heart development
 		%heart development sensu Insecta
 		%heart development sensu Mammalia
 			<atrium development
 
 It is sensical for 'atrium development' to only appear under the 
appropriate 'sensu branch'.  The model for this solution was the 
'chitin' example (see Usage Guide).
 
 A discussion ran during the pre-meeting around context sensitivity of 
Terms.  In the pre-meeting it was conceded that the goal should be 
making Terms context independent; the example was 'Suzie' vs. 
'Suzanna', which are used in different contexts but both refer to the 
same person.  It became clear during the main meeting, though, that 
such context independence is a difficult thing to achieve.  This issue 
was not aired in the main meeting.
 
 Note that it appears that David and Heather will be heavily involved in 
the addition of new high-level terms to the Process Ontology
 

 Anatomical Lexicons and GO
 
 The issue of incorporating anatomical information into the GO is 
intimately linked with the discussion ranging around the Process 
Ontology (see Process Ontology Discussion section).  There is a 
clear-cut boundary in the Process Ontology between Terms that can be 
abstracted from Anatomy and those that cannot.  Practically speaking, 
few processes peculiar to multicellular organisms have meaning when 
abstracted from anatomy, a particularly good example being 
developmental processes.  The general consensus is that 'when it gets 
multicellular, it gets complicated'.  As was pointed out above, a 
decision was made to incorporate Anatomies in the following manner:
 
  by using the pre-existing 'sensu' notation
  by restricting (initially) to class-level distinctions.  For instance, 
mouse will represent the class Mammalia; Drosophila will represent 
the class Insecta.
 
 This quite different from the conclusion reached in Hinxton, which was 
to eliminate anatomy from the existing GO Terms and introduce a 4th 
Anatomical Ontology.  Another major shift in this meeting vs. Hinxton 
is that the sentiment emerging from Hinxton was to eliminate 
multicellularity from GO; the sentiment emerging from this meeting is 
that multicellular processes should be incorporated into GO.
 
 DAG-based Anatomical Lexicons already exist for
  fly - available [DAG]
  mouse - available [DAG] (both developmental [public] and adult 
[not yet released])
  Worm - available
  Arabidopsis - being worked on by Leonore; plan to extend as a 
'standard plant anatomy'
  yeast - not available
 
 A proposed solution for representing anatomies in GO was made by 
Michael:
 
 GO ID:  12345
 Process:  Heart Development sensu Insecta
 Anatomical Component:  Heart with Anatomy ID (from 
Flybase Anatomical Lexicon)
 Reference ID
 Definition ID
 
 In this solution, each time a 'sensu' reference is made, an explicit 
reference to an Anatomical Lexicon is made, so that there need be 
nothing implicit in the definition of 'heart as in insects'.  By providing 
an Anatomical Lexicon cross-reference, a chief concern, drift, is 
addressed.
 
 A goal that emerged late in the meeting was to work toward an 
'Anatomy SLIM' that could represent high level anatomical structures 
across classes, though it is unclear where this will be taken.
 
 Granularity and the Purpose of the GO
 
 At several points the issue of what granularity should annotations of 
Gene Products be conducted to came up.  The general sentiment was 
that annotation should be done to the highest level of granularity 
available in order to provide an ontology that is useful for querying 
domain-specific databases.  Note that the stated utility here is in the 
GO's use in interrogating domain-specific databases, not across 
domains.  This muddies the waters somewhat in terms of what the 
goals of the GO Consortium are.  For instance, it appears that as 
multicellularity rears its head, the different organisms must part ways 
in terms of sharing Terms, though they could very well maintain 
congruence at the cellular and subcellular levels.  Perhaps a primary 
goal of the Consortium is not so much achieving Term congruence, but 
a common architecture for their domain-specific ontologies.  Given the 
emergence of the Sensu-solution for multicellular processes and the 
soon to be realized capability of exporting and importing DAG 
subsections, one could easily envision parallel but unlinked evolution of 
DAGs for the various represented organisms.
  Distinction between GO and Partner Databases
  The GO represents factual data
  The Partner Databases contain both factual and inferential 
data
 

 Progress Report - General
 
  only about 10% of GO ID's have corresponding Definitions
  the Oxford Dictionary of Biochemistry and Molecular Biology has 
been licensed by the GO Consortium (I believe that this is the text 
in question: http://www.oup.co.uk/isbn/0-19-850673-2).  
Definitions for GO Terms will be drawn from this text when possible.  
This text is not available in electronic form, though, and the notion 
of hiring temporary secretaries to type in definitions is currently 
being explored by Mike Cherry.
  What is the GO NOT
  The GO is not a database of gene sequences
  The GO is not a Federation solution
  The GO is not an edict
  A couple of brief notes
  in the pre-meeting (introductory) the Usage Guide and 
General Documentation were examined in detail and related 
to new comers.
  note that synonyms do not cover changes in case
  note that American spellings will be the default for Terms
  note that a GO ID is linked to the Definition, not to the Term; 
if the Definition changes, but the Term stays the same, the ID 
changes; the Term can change without the Definition or ID 
changing
  Michael brought up the notion that a 'Verification Tool' is 
needed that will take as input a file and GO IDs and Terms 
and will return a Diff file showing which have changed.
  LOGICAL RELATIONSHIPS..
 
 so, chromosomes
 
 telomeres are part of chromosomes
 mitochondrial chromosomes don't have telomeres
 so
 need linear chromosomes and circular chromosomes
 then organellar and bacterial chromosomes are instances of circular 
chromosomes
 and chloroplasts and mitochondria are instances of organellar 
chromosomes
 
 chromosomes
    linear chromosomes
       <telomeres
   circular chromosomes
        %organellar chromosomes
 	<mitochondrial chromosomes
 	<chloroplast chromosomes
 
 and so, to keep logical relationship 1 going, will continue to need to 
insert lines:.
 
 SO, IF PEOPLE SEE THINGS THAT DON'T MAKE #1 WORK, THEN 
NEED TO CHANGE IT:.
 ask Joel if he has some instances of this to send out for fixing or to fix 
himself:.
 
  Mapping GO to other Lexicons
  see also Progress Report: Prokaryotes & Protozoa
  In all cases, mapping will be to the finest granularity available
  It is possible that both a GO FAT and GO SLIM Term will be 
included in each mapping set (this would be very useful)
  Swissprot Keywords, handled by David.  Needs revisions due 
to substantial changes to the GO.
  Swissprot : there is the possibility that GO references will be 
incorporated into Swissprot records as database 
crossreferences, but there is a difference of opinion between 
the EBI and Geneva (Rolf & Amos), and Michael is unsure of 
the timeframe or format for a GO representation in Swissprot
  Interpro (release 2 was during the last week of October), 
handled by workers at the EBI (who?)
  EGAD and EC, handled by Michael
  MIPS : being planned, will be handled by Michael
  TIGR (with Michelle Gwynn) and Monica Riley's E. coli termset 
have been mapped, but cannot be made public.  Michael will 
be meeting with Claire Fraser in London and will discuss use 
of GO in TIGR annotations.
  A major concern among participants was the potential for 
proliferation of GO versions and interpretations among 
different databases, in particular between EBI and NCBI.  For 
instance, if the EBI annotates Swissprot to GO and the NCBI 
annotates RefSeq to the GO independently, there will be no 
mechanism for ensuring that the two annotations are 
coincident.  This is a major concern, that GO annotations be 
consistent for Gene X across all representations of  Gene X in 
the public domain.
  Human Annotation
  Meeting organized for December 11 at Banbury focusing on 
annotating human gene products.
  Human annotation is currently spread across many public and 
private groups with no centralized resource.  The MGI has 
taken a leading role in serving as a clearinghouse for 
mammalian standards, in particular standards as they relate 
to GO.
  The MGI is working to encourage groups to deposit thesauri 
and genesets to the GO site.
  Celera's Peter Lee implied at a recent nomenclature meeting 
that Celera might release a subset of their human data, 
annotated with GO.
  Sue Povey (spelling) of the human nomenclature group in 
London (HUGO?) has suggested that there may be a way for 
the GO to become a part of the HUGO nomenclature 
standard, though this consideration is at an early stage.
  Proteome has been talking of using the GO to annotated 
human genes.  At one time Proteome was considering 
working with the EBI and the ENSEMBL group, but they have 
perhaps shifted their focus to the NCBI (despite the NCBI's 
annotation pipeline being currently at an earlier 
developmental stage than the EBI's).
  Issue 1.  The GO should include all terms required to annotate 
human genes.
  Issue 2.  There should be harmony of annotation across all 
human genes; it would be counterproductive to have several 
different conflicting annotations.
  Issue 3.  Big Questions need to be answered:  What is GO 
and what is it not?  How can the GO facilitate human gene 
product annotation?  How can a unified annotation set be 
achieved?
  Issue 4.  There is some misunderstanding within the 
community that the GO is a replacement for COG or will 
replace existing gene family groupings; neither is true.
  Issue 5.  One victory condition:  convincing attendees that 
reverse-engineering the GO is not an option; need some 
checks about the currency of the GO
  Anticipated attendees at December meeting
  Representatives from Mouse, Fly, and Yeast 
communities
  2 or 3 folks from Celera
  Ken Fasman (AstraZeneca)
  Jim Garrels (sp) (Proteome)
  Donna Maglott (sp) (NCBI - LocusLink & RefSeq)
  Incyte (invited; not response to date)
  Sue Povey (human gene nomenclature & genetics)
  perhaps Lincoln Stein
  Micelle Clemm (EBI - Ensembl)
  a decision was made to invite someone from 
DoubleTwist (they have a curated set of human 
information and are interested in working with the MGI 
on mouse gene annotation)
  total <20 people; currently no funding available

  Evidence Codes & Documentation (Midori)
  when we say that we annotate to as low a level in the ontology 
as we have evidence to support, you can also annotate to lower 
and higher node as the evidence indicates:.
  remember that you can annotate 'not' for strong claims of 
evidence of the not:
  Heather had a question about the mutant phenotype category  
:.  she has a case a knowing something about gene product one 
as a result of knowing something about gene regulation by a 
mutant phenotype experiment knocking out another gene.  This 
should really be classed as a 'genetic interaction' with the 
citation:the citation gives the details of the experimental design.  
This will be written up as a 'case study'.
  Heather brought in example of where the evidence lines each 
give higher level, while author uses totality of evidence to infer 
lower level:therefore, use the lower level as TAS with citation.  
In the case of GO annotators, each database will create as 
necessary a reference citation of the GO annotation method and 
use that when the GO annotator combines evidence to infer 
function at the lower statement: (TAS).
  TAS  'traceable author statement'  could result in 'personal 
communication' abstracts on a per-instance basis.
  IEA  Inferred from Electronic Annotation  ISS means that an 
author in a paper has done a comparison of a mouse gene with a 
gene of another species or another mouse species: a curated 
analysis:.  IEA simply means that a compute has been done:in 
the mouse SP case, the SP record is known to relate to the 
mouse gene:but the GO annotation is based on the electronic 
translation of keywords:no one looked at each one.
  IEP is a valid code:to be used sparingly:.Kara has used for real-
old trashy northerns:
  IEA: Suzi didn't like the acronym, but will have to wait until next 
time if it's still an issue.
  ...and what every happened to Proteome
  The sentiment that 'Proteome used to be a nice company' 
was voiced by several.  Apparently Proteome has recently 
received venture capital funding and leadership has moved 
from the scientists to the business folks, with a coincident 
change in the tone of the their discussions with the GO 
Consortium.
 

 Progress Report - Flybase  (Michael Ashburner & Heather 
Butler)
 
  Major Revisions of GO subsections
  Process Ontology - transporters
  Function Ontology - nucleotide biosynthesis
  Function Ontology - some work on electron transport
  Process Ontology - stress response & stimulus (with TAIR & 
SGD)
  Of note - despite a number of major revisions, the number of terms 
obsoleted was quite small
  Database cross references to Milton Saier's transport classification 
(TC) where appropriate (analogous to EC database crossreference)
  Gene Annotations
  concentration on phototransduction (example)
  Working with Stefan (?) at the EBI to define edges between the 
Ontologies.  Stated that a curators script set is available for this 
purpose now.
  example ... if a protein is involved in de-ubiquitination, then it 
would also be used in the ubiquitination process
  Other than Drosophila menalogaster, there are no other insects 
currently being sequenced in the public domain, except perhaps for 
another Drosophila species (pseudoobscura?).  Exelixis is actively 
sequencing Insects, but they are not releasing them into the public 
domain.  There is a move in the community to sequence Bombyx, 
but the status of this effort is unclear.  Anopheles is on the NIH list 
to be addressed at some point, but this will require new techniques 
to handle host-parasite interactions.
 

 Progress Report - SGD  (Midori Harris, Mike Cherry)
 
  Nearly 2000 genes annotated now (by hand, by literature reading); 
working with in-house programmers to develop tools to update 
Oracle database, then generate a script to send to the GO site.
  Modest revisions to Component Ontology [with TAIR/Leonore] (see 
e-mail threads for details)
  Modest revisions to Usage notes regarding transitive relationships 
[with TAIR/Leonore]
  In the next few years, about 30 fungal genomes will be sequenced, 
2/3 of which are close relatives to Saccharomyces.  These will 
include Neurospora, Aspergillus flavus, etc.
  SGD has been solicited by >20 groups worldwide to handle 
nomenclature for Candida.  The Candida sequence is close to being 
completed.
  The pombe sequence is completed and the paper has been 
submitted for publication (Sanger group).  A GO annotation set has 
been submitted with external references being Swissprot IDs.


Progress Report - MGI (David Hill)

  GO Browser now publically available for MGI records 
(created/implemented by John Corradi)
  Gene-by-gene annotation of 15,000 genes
  effort is concentrated on moving IEA evidence to ISS 
evidence (or greater)
  updated annotations now being downloading to GO webpage 
every Friday
  Major Revision of GO subsections
  Process Ontology: apoptosis (with Flybase/Heather)
 
 

 Progress Report - TAIR (Leonore Reiser)
 
  Major Revisions
  Working (with Ji Yoon) on the introduction of terms into the 
three Ontologies to support Arabidopsis in the first instance, 
Plantae in general as a followthrough
  Plant terms - 162 total to date, 63 in the Component 
Ontology (50 with definitions)
  Expressed strong support for visual-based ontology curation and 
browsing tools
  Thesauri
  Worked on EGAD plant <> GO associations
  A contact has been initiated with Maize DB, but little feedback has 
been received to date (is this contact via Susan at Cornell?).
  A contact has been established at the Carnegie Institute within the 
Rice community regarding working with GO and Cyanobase
  A plant-related mailing list has been initiated
  The notion of a 'plant clearinghouse' for GO annotation is 
embryonic and being organized by Lenore and Richard Burkerist 
(formerly of the Sanger).
 

 Progress Report - Wormbase (Erich Schwarz)
 
  Erich is Paul Sternberg's first employee
  Wormbase growth
  Wen Chen (will be adding expression data to Wormbase 
AceDB)
  Raymond Lee (will be porting Wormbase from AceDB to other 
platforms)
  to fill one more curator's slot by summer & one db 
programmer
  Erich will be the GO-responsible party
  AceDB is beautiful for assisting in positional cloning.
  What is the relationship with Lincoln Stein?
  Invaluable
  He is on the grant that currently underwrites Wormbase
  Essential at the level of asking Lincoln to do things .. Lincoln 
put together the Wormbase.Org site at Paul Sternberg's 
request
  Eventually Wormbase will move from Cold Spring Harbor to 
CalTech
  relationship to Proteome ... they are using GO ... ?in the human 
curation?  General feeling is that the scientists have lost control of 
Proteome, the businessmen have smelled profit.  Proteome is 
helping out Worm by providing Worm database definition lines (?).
  relationship with the Sanger ... John Hodgin (gene mapping db) ... 
Sanger/WashU sequence feed ... very complex interaction map with 
other smaller dbs ... Richard Durbin involved as a subsidiary PI, like 
Lincoln Stein
  goal ... weekly updates rather than once every 3 months
 

 Progress Report - Prokaryotes & Protozoa
  Charlie Hodgkin (Glaxo; used to write software for Michael) initially 
contacted Michael and expressed his intention to use the GO for 
annotating E. coli.  This launched an e-mail flurry that eventually 
led to interaction between Michael and Heather, and Monica Riley 
and her postdoc Greta Serres (around ISMB '99).  Charlie, with 
Monica's support, is quite interested in putting the E. coli GO 
annotations in the public domain, but there is not indication of when 
this might be completed.
  Michael and Heather have mapped Monica Riley's latest (non-GO) 
classification to the GO, but it cannot be publicly released.  This 
mapping required the addition of many terms to the GO and has set 
up the GO for use for most enteric bacteria.  Monica has a great 
deal (10 years of work) invested in her classification scheme and 
has a great deal of interest in seeing a proper mapping/merge 
between GO and her scheme.
  Michael and Heather have also obtained from Monica Riley the 
Genprotec enzymes list (a list of E. coli proteins), and this has been 
parsed into the Function Ontology.
  The situation around EcoCyc is complicated and it is unclear when 
EcoCyc <> GO mapping might be done.  EcoCyc ownership is being 
resolved between DoubleTwist, Pangea (now DoubleTwist), and 
SRI; an NIH grant (content unknown) is being held up pending 
resolution.
  There is an interest at Stanford in annotating cyanobacteria with 
GO, but it is unclear where this is going in the near term.
  A previously noted protist interaction is dead (Russ Altman?) : a 
Canadian group has recently become interested in annotating 
protists with the GO in conjunction with some large scale 
sequencing.
  There is currently no activity on the horizon for annotating viruses 
with the GO.
  The group has not looked at the 'minimal microbial genome' to see 
if it is fully represented in the GO.
  Michael would like to see Pseudomonas included (for its xenobiotic 
metabolism) and Streptomyces (for its antibiotic biosynthesis)
  Three groups have independently applied for funding to the 
Wellcome Trust for the sequencing of 3 different protozoa 
(leishmani, trypansoma cruzi, and trypansoma bruceii), in close 
collaboration with a new plasmodium database at the University of 
Pennsylvania.  Al Ivans (Sanger), who I presume is attached to one 
or more of these, is interested in using the GO in their gene 
annotations, though nothing is firm to date
  General message:  would like to identify communities, work to build 
a foundation for them, then invite them to build on that foundation

 Software Developments
 
  A relational database containing the GO terms is now available.  It 
was unclear to me whether this is in Oracle in addition to MySQL, 
but that is not really relevant at this juncture.
  The time is imminent when the following will be available to 
curators:
  direct writes to a pre-production (development) database 
instance
  elimination of duplicate ID and basic syntax errors owing to 
data integrity functions (currently no data integrity ... 
everything done as flat textfiles).
  Curation interface with undo, DAG view, and commit 
functionality (see below)
  Rollback to previous version, owing to audit trail functions
  Java Browser (John Richter)
  Online at fruitfly.org
  Demonstration was very well received by participants
  A lot of effort has gone into making the browser platform 
independent
  All GO terms in all three Ontologies are found in a single tree 
(one window in Browser)
  Clicking any term brings up a minimal DAG in an accessory 
window
  Queries run as Perl5 regular expressions
  Query Window supports either Boolean or Perl5 regular 
expression queries
  After pulling a gene product, can click on a term block and 
thereby highlight the terms in the Ontology Tree Window; the 
minimal DAGs are also shown for these terms in an accessory 
window
  The number of gene products is no longer indicated in the 
interface
  Java Editor (John Richter)
  The editor will have the same look and feel as the Browser 
when completed
  Editor runs as an application rather than as an applet; it is 
available under CVS and must be installed to be used
  GO ID is fixed; new terms get automatic assignment (there  
was brief discussion around how to assign ID's which did not 
reach final resolution; currently, ID ranges are apparently 
assigned to curation groups)
  Structrual Edits (edits to the DAG structure)
  simple select/click/drag to change structure
  'infinite' undoes
  term-merge by click/drag; one term lives on while the 
other is obsolesced and becomes a synonym of the live 
term
  term-splitting enabled (do not recall details)
  term obsolescence is automatic if all children are obsolesced
  cyclic graphs are not automatically disallowed; thus curators 
need to avoid descent along obsolesced terms
  For searches, obsolesced terms should all be treated as 
leaves
  Rollbacks:  In theory, 'infinite' rollback is possible, but there 
is currently no 'History Viewer' and John suggested that 
design of one would be significantly more complex than either 
Browser or Editor.
  Logic Validation is currently not within the remit of the Editor
  Erich:  would like to have a visual cue that indicates which 
terms have been changed recently
  Provides for tagging a term as part of GO Slim, and capability 
of adding any number of additional segregation tags in the 
future.
  Import & Export of subtrees will soon be available (a very 
useful feature)
  A Gene Product Viewer will be added in the near future, the 
nature of which is currently unknown.
  Technical Discussion : aiming for a Generic Ontology Builder
  The current Editor is componentized
  The DAG component is generic, not specific for GO
  Using Java components has allowed fancy click/drag 
functionality, including a smooth table resizer
  All components are available on the CVS repository : with 
DOCUMENTATION (fancy that)
  The GO Schema is available at 
www.fruitfly.org/annot/go/database/index.html
  People are encouraged to write ports to different database 
formats and submit them to the GO Database mailing list
  HTML Browser (Brad Mars)
  The HTML Browser is running off of the GO Relational 
Database (Chris Mungall's Perl API) rather than off of the GO 
Flatfiles, as the Java Browser does currently
  found at http://www.fruitfly.org/~bradmars/cgi-
bin/go.cgi?accession=3700
  Similar : though generally weaker : functionality to the Java 
Browser.  Plans are to increase functionality to be on par with 
the Java Browser
  BLAST Server (Suzanna Lewis)
  There is an obvious need for the ability to BLAST against 
organism sequence sets using sequences retrieved via GO 
searches.
  An unasked question : why do they not rely on the archival 
databases to serve BLASTs?
  There was some discussion around whether to have 'all 400 
version of ADH' included or not
  The current thought is to have protein sequences in fasta-
format deposited on the GO website and available for Blast 
searches
  In the case of MGI, the plan is to submit a single protein 
sequence per gene.  This single sequence will be the primary 
Swissprot sequence that represents each gene prouct.  MGI 
annotation is to the level of the gene, not to the gene 
product; therefore, spliceforms and post-translational 
modifications do not matter that much to them at this point in 
time.
  In the case of yeast, about 2000 yeast protein sequences 
have already been provided.  The fasta header line for the 
yeast sequences was discussed as a standard.
  general syntax : key:value[space] (key order not 
constrained)
  'provide everything that you can provide, the more the 
better'
  community name for the gene (that used locally within 
a particular domain)
  gene name (the generally accepted, or global name for 
the gene)
  tab delimited list of GO ID's
  one or more external database cross-references
  Timing, Resource, and Prioritization Issues
  The primary software developers associated with the GO 
Consortium are John Richter and Chris Mungall.
  John is the primary driver behind development of the Java 
Browser and Editor, which appear to be the currently favored 
for GO delivery to end users and curators.
  About 3 weeks of work remain (according to John) to reach a 
final stage on Java Editor & Browser
  John is currently under obligation for development of an 
open-source gene annotation platform, Apollo, and timing for 
completion of software development for the GO Consortium is 
currently critically dependent upon his obligations to Apollo.
  Also competing for resource is a Fly Genome Reannotation 
project that is on-going.
  There is significant concern (voiced by Michael) around the 
absence of rigorous syntactic control and internal checks.  
John indicated, though, that syntactic checking algorithms are 
'the stuff of papers' and were going to devour the majority of 
the development time.  (I am quite fuzzy on exactly what the 
issue is here).
  The concern was voiced that the GO DAG could be really 
screwed up if the Editor is used improperly ... powerful tools 
mean powerful edits.  However, the potential for rollbacks 
really softens the potential impact of this problem.
  Suzanna voiced the opinion that the priority lay in getting out 
of flatfile mode and into a relational database environment.  It 
seemed that most everyone agreed with this.
  A key untackled problem appears to be 'how to commit DAGs 
to a database,' which apparently both John and Judy are 
thinking hard about.  (again, I'm not quite clear on what this 
issue is here.)
  Interim Solution during resource-limited period
  John will do enough so that the Java Editor is available and 
will produce flatfiles; the flatfiles will be fed to the GO via the 
currently implemented CVS system.
  Downloads from the 'outside'
  Data is currently provided to external parties on an ad hoc 
basis.  The mySQL database can be downloaded with the 
following caveat:  'If you make any changes, do not publish 
this database'.  Among the groups who have downloaded is 
AstraZeneca (Bo Servenius, Lund, Sweden).
  Presumably, people are writing applications on top of the 
database, so John is trying to give a lead time on large 
changes.
  A Perl Development Kit has been assembled to assist in the 
loading/updating of external representations.
  A defined update/error reporting process has not been set up 
to date.  However, each of these is currently handled through 
the e-mail lists (GO-FRIENDS, GO-DATABASE, GO-DIFF).
  The contact points should probably be Chris Mungall and John 
Richter.  Send format problems to John Richter 
(http://www.fruitflyorg/annot/go/) and suggestions to John at 
go-admin@bdgp.lbl.gov
  Right now, remote access is relatively slow, presumably 
because there is lots of SQL being done remotely.  John and 
Chris have some ideas bouncing about regarding 'fast access 
to GO Objects'.  Consult John on this matter.
 

 Discussion around the Editing Process
 (various) (see also Software Development: Java Editor)
 
  Judy:  a database administrator would help to stem the proliferation 
of terms and provide some control over the process
  Still trying to resolve the issue of how to distribute editing to a 
database globally across groups and disciplines.  A software tool is 
emerging (Java Editor, design by John Richter) but the issue of 
editing control is still being debated.
  Michael:  Minor Changes - Just commit them; Major Changes - 
consult the group via e-mail and commit after period (currently ~10 
days); Really Major Changes - talk in person.
  Michael does not really want to see the current process changed.  
There was some discussion between Michael and Judy around 
similarity between the GO and extant nomenclatures, where 
committees meet to commit changes, but Michael would really want 
to avoid the potential emergence of bureaucracy, favoring 
maintenance of the present 'sociology' around the GO Consortium.
  It was generally accepted that there should be both a Working 
Database (Development) and an Authoritative Database 
(Production).  There was some split of opinion over whether the 
Working Database should be publicly visible, but it appears that it 
will be made so, the argument being that the more skilled eyes that 
are looking at the work in development, the better.
 

 Schema Discussion, with emphasis on DBxREF
 
 A discussion ensued around whether the DBxREF field should refer to 
Terms and Definitions in the aggregate or separately.  This discussion 
gets to the issue of whether a particular piece of information derived 
from a Source should be traceable to the Source or not.  The current 
record structure looks like this:
 
 GO ID
 Term
 Definition
 Definition Refs
 Synonyms
 Synonym Refs
 DBxREFS (+ Boolean; supports Definition, Term, etc.)
 
 Suzanna led the discussion around proposed changes to the Schema.
  suggest adding a 'subclass' table to support tags that allow quick 
segregation of the GO into subsets (such as GO SLIM).
  suggest addition of sequence relationships to support sequence 
accession number searches, with coincident links to Gene Products
  Suggest addition of a type flag to the term_dbxref table to allow 
Term vs. Definition (or other type) values to be distinguished.  Also, 
suggest addition of DBxREF tables as needed around other value-
sets (such as synonyms)
 

 Trademark (Mike Cherry)
 
  A copyright statement has been added to the GO Consortium Page
  A logo [designed by John Matese] is available for the GO 
Consortium (found on 
http://www.geneontology.org/GO.usage.html; specifically 
http://genome-www.stanford.edu/images/GOthumbnail.gif)
  The Trademarking/Copywriting issue comes up now as more people 
become interested in using GO and the potential for product 
developers to incorporate GO without attribution or in an 
independent but apparently associated manner increases.

 GO SLIM
 
 The utility of GO SLIM was generally recognized.
 
 A referent/cutout/subclass table will be added to the GO Relational DB 
that will allow extraction of GO SLIM, GO FAT (full), Plant Terms, and 
other term subsets.
 
  Utility of GO SLIM
  Initially needed for high level Celera annotation
  Subsequently needed for Riken Annotation Jamboree 
(FANTOM meeting)
  this was apparently an effort to annotate by 
'computational means' about 2000 previously 
undescribed mouse cDNAs
  11 methods were used and a manuscript is apparently 
being assembled
  one thing that the group rues is the absence of an 
upfront comparative metric between the 11 methods; 
they could tease out a comparison between the 
methods, but it would be tedious, though perhaps worth 
it
  This effort involved the MGI (David) and took place 
around the time of the global genomics meeting in 
Japan
  Problem:  The GO SLIM used for Celera and Riken were not 
identical
  Useful for easy to apprehend graphics, such as pie charts
  Useful for high level classification, such as across genes in a 
microarray experiment
  Potentially more stable than full GO (though this is not a 
sentiment shared by all participants).  In particular, the 
'lower half' of the Process Ontology is in flux.
  Status of GO SLIM
  Currently maintained by hand (by Michael)
  One outcome of meeting was a decision to added a GO SLIM 
entry to each Gene Product annotated.  A commitment to 
automating this process was discussed.  This GO SLIM view 
would be included in Swissprot and NCBI representations 
alongside the GO FAT view.
  The current criterion for a term being part of GO SLIM is 
'someone says so'.
  There is no intrinsic connotation to the node-levels in GO.  
This means that there is nothing inherently similar among 
terms at Level 3, for instance.  Thus, the slice through the 
Ontologies that would define GO SLIM is necessarily ragged 
(occurring at different levels for different branches).
  Currently no alerting system to highlight changes in GO SLIM; 
requires consultation of DIFF files and manual extraction.
  Most recent version 100-150 terms; see Appendix A.

 Funding
 
  The GO Consortium expects to receive full funding for pending 
grants.
  Funding is for 3 years beginning 1 December 2000
  There is currently an administrative (Congressional Budget) delay 
on the disbursement of funds.
  Funding is initially to support 3 groups in the GO Consortium 
(Mosue, Yeast, Fly), with the addition of 2 groups after the 1st year 
(presumably Arabidopsis and C. elegans).
  Other funding ... Incyte (no details) ... AstraZeneca (no details)
 
 Publications
 
  A Genome Research paper is in the process of being written (GO 
Consortium), which will provide more details on the GO and is a 
followthrough from the Nature Genetics paper recently published.
  A Genomics paper is in the process of being written (MGI) which will 
detail some of the recent mouse gene annotations incorporating the 
GO
 
 Next Meeting
 
  3, 4, 5 March
  Palo Alto, CA
  hosted by Sue Rhee, Carnegie Institute, Stanford University

Immediate Actions

Doug:send THE LETTER to him to for DoubleTwist:.invite them to Dec. 
meeting:.CALL ANDREW AND ASK HIM WHO TO SEND THE LETTER 
TO:EXPLAIN THE SITUATION..
review John Richter's FAQ about GO page:
WE NEED TO SEND FASTA/GO FILE TO GO-SLIM
WE NEED TO POST AT mgi THE mgi/GO FILE THAT IS SENT TO 
www.geneontology.org


Appendix A:  Current GO SLIM

From: 	Suzanna Lewis[SMTP:suzi@bdgp.lbl.gov]
Sent: 	Wednesday, October 25, 2000 11:34 AM
To: 	ma11@gen.cam.ac.uk; midori@genome.Stanford.EDU; 
suzi@bdgp.lbl.gov
Cc: 	go@genome.Stanford.EDU; dph@titan.informatics.jax.org
Subject: 	Re: go_slim


also needed to add unlocalised to component slim.

here is the updated version

$Gene_Ontology ; GO:0003673
 $cellular_component ; GO:0005575
  %cell wall ; GO:0005618
  %extracellular ; GO:0005576
   <extracellular matrix ; GO:0005578
    <basement membrane ; GO:0005604
   <extracellular space ; GO:0005615
  %intracellular ; GO:0005622
   %cell ; GO:0005623
    <nucleus ; GO:0005634
    <chromosome ; GO:0005694
     <chromatin ; GO:0005717
    <cytoplasm ; GO:0005737
     <mitochondrion ; GO:0005739
     <lysosome ; GO:0005764
     <endosome ; GO:0005768
     <vacuole ; GO:0005773
     <peroxisome ; GO:0005777
     <synaptic vesicle ; GO:0008021
     <endoplasmic reticulum ; GO:0005783
     <ER-Golgi intermediate compartment ; GO:0005793
     <Golgi apparatus ; GO:0005794
     <lipid particle ; GO:0005811
     <microtubule organizing center ; GO:0005815
     <spindle ; GO:0005819
     <cytosol ; GO:0005829
      <26S proteasome ; GO:0005837
     <ribosome ; GO:0005840
     <cytoskeleton ; GO:0005856
      %actin cytoskeleton ; GO:0015629
      %microtubule cytoskeleton ; GO:0015630
       <microtubule ; GO:0005874
      <intermediate filament ; GO:0005882
    <plasma membrane ; GO:0005886
     <intercellular junction ; GO:0005911
    <cilium ; GO:0005929
  %unlocalised ; GO:0005941
  %cellular_component unknown ; GO:0008372
 $biological_process ; GO:0008150
  %cell growth and maintenance ; GO:0008151
   %metabolism ; GO:0008152
    %carbohydrate metabolism ; GO:0005975
    %energy pathways ; GO:0006091
    %electron transport ; GO:0006118
    %nucleotide and nucleic acid metabolism ; GO:0006139
     %DNA metabolism ; GO:0006259
      %DNA replication ; GO:0006260
      %DNA repair ; GO:0006281
      %DNA packaging ; GO:0006323
     %transcription ; GO:0006350
    %protein metabolism and modification ; GO:0006411
     %protein biosynthesis ; GO:0006412
     %protein folding ; GO:0006457
     %protein modification ; GO:0006464
     %proteolysis and peptidolysis ; GO:0006508
    %amino-acid and derivative metabolism ; GO:0006519
    %protein targeting ; GO:0006605
    %lipid metabolism ; GO:0006629
    %monocarbon compound metabolism ; GO:0006730
    %coenzymes and prosthetic group metabolism ; GO:0006731
   %transport ; GO:0006810
    %ion transport ; GO:0006811
    %carbohydrate transport ; GO:0008643, GO:0008644
    %amino-acid transport ; GO:0006865, GO:0006866
    %nucleobase, nucleoside, nucleotide and nucleic acid transport ; 
GO:0015931
    %drug transport ; GO:0015893
    %lipid transport ; GO:0006869
    %mitochondrial transport ; GO:0006839
   %ion homeostasis ; GO:0006873
    %exocytosis ; GO:0006887
    %endocytosis ; GO:0006897
   %intracellular protein traffic ; GO:0006886
   %cell death ; GO:0008219
   %cell motility ; GO:0006928
   %stress response ; GO:0006950
   %cytoplasm organization and biogenesis ; GO:0007028
    %ER organization and biogenesis ; GO:0007029
    %Golgi organization and biogenesis ; GO:0007030
    %peroxisome organization and biogenesis ; GO:0007031
    %endosome organization and biogenesis ; GO:0007032
    %vacuole organization and biogenesis ; GO:0007033
    %lysosome organization and biogenesis ; GO:0007040
    %intercellular junction assembly ; GO:0007043
    %organelle organization and biogenesis ; GO:0006996
     %mitochondrion organization and biogenesis ; GO:0007005
     %cytoskeleton organization and biogenesis ; GO:0007010
      %microtubule-based process ; GO:0007017
   %cell proliferation ; GO:0008283
   %cell cycle ; GO:0007049
  %cell communication ; GO:0007154
   %cell adhesion ; GO:0007155
   %signal transduction ; GO:0007165
  %developmental processes ; GO:0007275
  %physiological processes ; GO:0007582
  %sensory perception ; GO:0007600
  %behavior ; GO:0007610
  %biological_process unknown ; GO:0000004
 $molecular_function ; GO:0003674
  %nucleic acid binding ; GO:0003676
   %DNA binding ; GO:0003677
    %DNA repair protein ; GO:0003685
    %DNA replication factor ; GO:0003687
   %RNA binding ; GO:0003723
    %transcription factor ; GO:0003700
   %translation factor ; GO:0008135
  %transcription factor binding ; GO:0008134
  %cell cycle regulator ; GO:0003750
  %cytoskeletal regulator ; GO:0008580
  %chaperone ; GO:0003754
  %motor ; GO:0003774
  %defense/immunity protein ; GO:0003793
  %enzyme ; GO:0003824
  %enzyme activator ; GO:0008047
  %enzyme inhibitor ; GO:0004857
  %apoptosis inhibitor ; GO:0008189
  %toxin ; GO:0015070
  %signal transduction ; GO:0004871
   %receptor ; GO:0004872
   %receptor signalling protein ; GO:0005057
   %ligand ; GO:0005102
  %cell adhesion ; GO:0005194
  %storage protein ; GO:0005187
  %structural protein ; GO:0005198
   %cytoskeletal structural protein ; GO:0005200
   %structural protein of ribosome ; GO:0003735
  %transporter ; GO:0005215
   %ion transporter ; GO:0015075
   %carbohydrate transporter ; GO:0015144
   %amino-acid transporter ; GO:0015171
   %nucleobase, nucleoside, nucleotide and nucleic acid transporter ; 
GO:0015932
   %neurotransmitter transporter ; GO:0005326
   %drug transporter ; GO:0015238
   %lipid transporter ; GO:0005319
   %channel/pore class transporter ; GO:0015267
   %carrier ; GO:0005386
    %primary active transporter ; GO:0015399
   %group translocator ; GO:0015455 ; TC:4.-.-.-.-
  %ligand binding or carrier ; GO:0005488
   %electron transfer ; GO:0005489
   %protein binding ; GO:0005515
    %actin binding ; GO:0003779
    %tubulin binding ; GO:0015631
  %protein tagging ; GO:0008638
  %ribosomal RNA ; GO:0005566
  %small nuclear RNA ; GO:0005570
  %small nucleolar RNA ; GO:0005569
  %transfer RNA ; GO:0005563
  %antisense RNA ; GO:0009388
  %molecular_function unknown ; GO:0005554
$
GO Consortium Meeting, 5-6 Nov 2000

1