Using Annotation to Drive Ontology Development

Comprehensive Annotation can Drive Ontology Development Blood Pressure Regulation Real-world Example

Middle of November: Decided to focus on genes having to do with blood pressure regulation We had three terms in the ontology To describe blood pressure regulation

Next step-READ! Used a standard medical textbook to learn about the physiology of blood pressure

December 1, 2005 Propose a basic structure in a SourceForge item

December 1-19,2005 Lots of Discussion Consult outside experts.

December 19, 2005 Added 43 new terms Harold adds the new terms And relationships to The “live” GO.

December 20, 2005-, 2006 Read Papers and Annotate Genes!  December 22, five new terms  December 23, two new synonyms, two new terms  December 27, six new terms  December 28, three new terms  February 27, seven new GO terms Not all of these were about blood-pressure regulation, some of them were needed to annotate genes that are involved in other processes

Annotating Papers Results In  Improvement in parts of the GO outside the area of focus –If the original first pass was good, most of these are new leaf nodes  More genes than the initial set that have to do with the process of interest.  Annotations of genes to processes other than the one of primary interest

Steps in Comprehensive Annotation Identify papers Read papers Modify GOCurate papers A B C D E

Where are we now? The Good News  On December 1 st - –14 genes annotated to blood pressure regulation –65 annotations to those genes  Two weeks ago –23 genes annotated to blood pressure regulation –264 annotations to those genes –5 genes have all literature annotated  Other genes get annotated as papers get annotated  Not all annotations have to do with blood pressure!

Where are we now? The Bad News There is still an outstanding Sourceforge Item about the terms in this part of the graph

WHAT HAPPENED? I short-circuited the process!

Steps in Comprehensive Annotation Identify papers Read papers Modify GOCurate papers A B C D E X X

Why was the process short- circuited  The ontology issues outstanding are relatively minor  I could still annotate papers as the ontology stood  I felt that my time could now be spent on annotations-I switched my primary role from an ontology developer to an annotator.

How can we prevent short Circuits?  Clearly there has to be an assignment of responsibility for the ontology development –The responsibility begins with expert curators representing the biology –The responsibility continues with ontology developers who must point out major logical issues Major logical issues should be dealt with by expert curators –Minor issues should be then addressed as concrete proposals by ontology developers Minor issues are either accepted or rejected by curators –Final decisions are made based on whether the ontology represents the biology

A Proposal Given that we plan to go the route of reference genome annotation, let’s try an experiment

Neurobiology Interest Group Meeting: June 14-15,2006 Focus on Central Nervous System Development

Identify Reviews That Will Serve as the First Step of Ontology Development

Use Reviews to Create the First Pass

Triage the Literature in the Reviews This review cites 291 references!

What does triage mean?  Identify papers that are of use  Identify reference-genome organisms that are studied in those papers  Identify genes that are in those papers

Assign Papers to Curation Team Members  Curators are responsible for fully curating papers that are assigned to them  Curators are responsible for adding to/modifying the ontology as necessary  Track progress of genes, annotations and terms  Curators are then responsible for assessing the completeness of gene annotation in their MOD.