1. Comprehensive Annotation System for Infectious Disease Data Alexander Diehl University at Buffalo/The Jackson Laboratory IDO Workshop 2010 12/9/2010

2. Comprehensive Annotation System for Infectious Disease Data in a Model Organism Alexander Diehl University at Buffalo/The Jackson Laboratory IDO Workshop 2010 12/9/2010 of

3. The Gene Ontology Three linked ontologies: – Biological Process operations or sets of molecular events with a defined beginning and end, pertinent to the functioning of integrated living units: cells, tissues, organs, and organisms – Molecular Function the elemental activities of a gene product at the molecular level, such as binding or catalysis – Cellular Component the parts of a cell or its extracellular environment www.geneontology.org

4. The Gene Ontology Many Terms: – 33103 terms (as of 12/7/10) 19950 biological_process 2781 cellular_component 8910 molecular_function Many Annotations: – 461487 genes annotated (as of 12/4/10) 354119 biological_process 379529 cellular_component 320525 molecular_function amigo.geneontology.org

5. The Gene Ontology and Infectious Disease GO Immunology revision of 2006 resulted in 700+ new terms for describing immunological aspects of gene products. Over 1000 terms in current GO describe immunologically related properties of genes. The PAMGO group (Plant-Associated Microbe Gene Ontology) prepared over 900 terms for GO between 2005-2009 to cover aspects of interactions between organisms, including processes related to infectious diseases.

6. The Gene Ontology and Infectious Disease adhesion to host – Type IV pili-dependent localized adherence to host response to bacteria adaptive immune response – immunoglobulin mediated immune response evasion or tolerance of host immune response

7. 7 The association of a gene product (protein) with a GO term based on experimental data constitutes a GO annotation. The data itself is an instance. The annotation relates that instance to a type, a GO term. GO annotations are publicly available via the GO Consortium’s Amigo browser, http://amigo.geneontology.org GO Annotation

8. 8 Structure of a GO annotation: – Gene product identifier – GO term – Evidence Code IDA, IMP, IPI, ISS, IEA – Reference – Extended Annotation Data Anatomy Cell type Target of process Isoform used Dual-taxon ID GO Annotation

13. GO Annotation of Genes Involved in Host Responses to S. aureus Selected papers for annotation that used S. aureus as a model pathogen for study of host responses in the mouse. Annotated 25 papers of an initial selection of over 60 identified papers. GO annotations entered using Mouse Genome Informatic’s editorial interface. The annotations are available at MGI, and have been propagated to AmiGO, NCBI, and QuickGO.

14. Annotation Effort 295 annotations generated for a variety of gene products involved in response to S aureus and other pathogens, including NOD2, TLR2, TLR4, IL- 10, CD36, Scd1, and others. Anatomical details, cell type ID, taxon IDs, and specific strain information collected where appropriate. Some annotations are made to human genes and appear for orthologous mouse genes as ISS annotations.

15. Value of this Annotation Set Provide representation of key GO processes for genes involved in responses to pathogens. Strengthen the utility of GO in term enrichment analysis of gene sets, e.g. microarray experiments. Drives development of new terms for the GO, “annotation-driven ontology development.” – 44 new GO terms were created.

16. A More Comprehensive Approach Collect additional information from paper or study in the form of ontology terms describing details of experiment method, organisms and reagents used, and relations between experimental components. Provide a convenient “annotation ID” that enables easy reference to a particular annotation. Link individual annotations to draw more complex conclusions.

18. Enhanced GO Annotation for Infectious Disease Ontology

26. Conclusions Comprehensive manual annotation can rely on all OBO-Foundry ontologies and other taxonomies. A variety of material entities and qualities can be annotated. A system of annotation dependencies can be built to allow for more complicated chains of inference. Such a system can leverage existing GO and MP annotation where appropriate. Collections of annotations can be modeled into a BFO- based application ontology for a particular domain.

27. A proto-MS application ontology

28. 28 Acknowledgments MGI Judith Blake Jason Bubier Duke University/UT Southwestern Lindsay Cowell