1. Development and Use of Controlled Vocabularies at the Arabidopsis Information Resource (TAIR) Sue Rhee Carnegie Institution Dept. Plant Biology rhee@acoma.stanford.edu

2. TAIR http://arabidopsis.org A model organism database for Arabidopsis thaliana Current major data types: community (~11,000 people, ~4,000 labs) literature (~12,000 articles, ~450 reviews) genes and proteins (~29,000 genes, ~28000 proteins) alleles and polymorphisms (~150,000) germplasms (~150,000, ~1000 mutant, ~800 ecotypes ) ‘expert’ gene families (~450 containing ~4000 genes) microarray data (~130 experiments, ~600 hybridizations) metabolic pathways (~170 pathways, ~1000 reactions)

3. Controlled Vocabularies Existing: GO function, process, component Arabidopsis anatomy, developmental stages Under development: experimental methods environmental factors PO anatomy, developmental stages Planned: PO trait Needed: chemical values? (qualitative and quantitative)

4. Developing controlled vocabs Anatomy Developmental Stages Methodology Using controlled vocabs Gene and gene product functional annotation Community Microarray experiments and array elements Alleles Germplasm

5. Purpose for Anatomy and Developmental Stages Ontologies To describe things like: where is a gene expressed in the plant at what stage of development was the plant when the RNA sample taken from what tissues was the protein sample derived what part(s) of the plant are affected in a mutant line

6. Anatomy and Developmental Stages anatomical parts (295) developmental stages (69) Sources Katherine Esau (1960) The Anatomy of Seed Plants John Bowman (1994) Arabidopsis An Atlas of Morphology and Development Meyerowitz & Somerville ed. (1994) Arabidopsis An Atlas of Morphology and Development Numerous primary articles and websites on development/anatomy Stanley Letovsky, Cereon Genomics Doug Boyes, Paradigm Genetics Leonore Reiser (TAIR), Jonathan Clarke (JIC)

7. Rules for Anatomy and Developmental Stages Ontology Development Terms from literature and text books that describe anatomy and development (364 terms; 221 defs). For anatomy- the terms must describe parts that are found in Arabidopsis (limited scope). Developmental stages should be based on morphological features- regardless of a time component as different accessions reach the same stage at different times. An example is the floral developmental stages defined by John Bowman.

8. Created separate anatomy and developmental stages as directed acyclic graphs. Tried to make the graphs orthogonal in order to generate cross products easily. Creating cross products between stages and anatomy (what parts exist at what stage?) Creating cross products with developmental process terms. Used DAGEditor (BDGP) for ontologies and eventually making cross products. Methods for Anatomy and Developmental Stages Ontology Development

9. Ontologies for Anatomy and Development

10. Crossing Anatomy and Developmental Stsages etc.etc.etc…

11. Current Status 221/364 terms are defined. Terms (definitions and relationships) are checked for accuracy (external review and literature). Being used to annotate genes and products Files available on GOBO and TAIR ftp sites In collaboration with MaizeDB and Gramene on sharing the ontologies to build a common plant ontology (probably flowering plant…)

12. Developing Methods Ontology (An ontology of experimental techniques) Sources: short, semi-controlled description of experimental information during annotation (102) protocols from the research community (152) microarray experiments (129) Current status: DAG structure 195 terms and 3 definitions more structure revision needed Leonore Reiser, Margarita Garcia-Hernandez, Gabe Lander

13. Developing controlled vocabs Anatomy Developmental Stages Methodology Using controlled vocabs Gene and gene product functional annotation Community Microarray experiments and array elements Alleles Germplasm

14. Currently Annotated Data Types Genes and gene products (2931) –molecular function (2599 genes to 296 terms) –biological process (536 genes to 269 terms) –subcellular location (695 genes to 104 terms) –Anatomy & devel. Stages (117 genes to 50 terms) –spatial and temporal expression pattern (110 genes to 52 terms) Community (2415 comm. to 2892 terms) –research interest (2737 terms) –organism of interest (192 terms)

15. Basic Process of Literature Curation Subject termObject term Paper Binds to Involved in Functions as Expressed in Is subunit of Related to Required for Located in Interacts with Regulates More… data object (e.g. gene) controlled vocabulary data object automatic manual Currently 20 types

16. Pubsearch Statistics (10/02) Data typesunique matched (unique papers) Genes3182 (7485), 8.9% GO process terms653 (8439), 9.5% GO function terms830 (6537), 15.2% GO component terms266 (5686), 23.1% Anatomy/develop terms213 (5583), 58.5% | development | 2531 | | growth | 1900 | | transcription | 1114 | | biosynthesis | 865 | | flowering | 697 | | transduction | 684 | | transport | 659 | | signal transduction | 625 | | germination | 455 | | metabolism | 425 | | binding | 1494 | | enzyme | 1184 | | kinase | 637 | | receptor | 433 | | beta-glucuronidase | 413 | | protein kinase | 309 | | hormone | 302 | | DNA binding | 299 | | transcription factor | 269 | | transporter | 230 | | cell | 2487 | | membrane | 1031 | | chromosome | 842 | | chloroplast | 604 | | plasma membrane | 408 | | cell wall | 291 | | plastid | 270 | | nucleus | 258 | | intracellular | 236 | | host | 230 | TOP TEN LISTS

17. PubSearch Annotation User Interface

19. Expanding Data Objects to Annotate microarray experiments RNA samples array elements (ESTs, oligos, PCR products) alleles (natural variant & mutant forms) germplasm (ecotypes & mutant lines)

20. Microarray Data Annotation Experiments goals (e.g. GO process) variables (e.g. anatomy, environment, chemical) need a qualifier (e.g. values ontology?) type/category (e.g. methods) RNA Samples germplasm biomaterial (e.g. anatomy, devel. stages) external conditions (e.g. methods, envirnoment, chemical) Array elements affected by/in XXX (e.g. GO process, anat, dev) induced during/in XXX reduced during/in XXX

21. Phenotype Annotation Trait Condition environment chemical Methodology TraitValue Germplasm hy4-1 mutant linelong height measure with ruler light ConditionValue absence Anatomy Biol. Process etc… hypocotyl

22. Expanding Types of Annotations By using more relationship types rather than more terms in an ontology. For example: Gene to gene family –Relationship type: is a member of Molecular interactions –Relationship types: represses, activates, binds to Genetic interactions –Relationship types: suppresses, enhances

23. A model of control of flowering in Arabidopsis From “Molecular Genetics of Plant Development”

24. Generating the image from the database Gene1RelationshipGene2 ELF3RepressesGA1 ELF3RepressesSPY ELF3ActivatesEMF1 Represses = Activates = ELF3GA1 ELF3GA1, SPY ELF3GA1, SPY EMF1

25. Genetic Interaction / Transcriptional Regulation Pathways

26. Acknowledgements Leonore Reiser Tanya Berardini Suparna Mundodi Margarita Garcia-Hernandez Eva Huala Lukas Mueller Peifen Zhang Aisling Doyle, J. Yoon, Gabe Lander Danny Yoo, Iris Xu Jonathan Clarke (John Innes Institute) GO, TIGR, Monsanto, MaizeDB, Gramene, SRI International

27. Where to get our stuff ontologies and annotations (ftp site) ftp://ftp.arabidopsis.org/home/tair/Ontologies/ annotations (search & download ) http://www.arabidopsis.org/info/ontologies/ literature curation software-pubsearch (download) http://www.gmod.org/

28. Sources of Vocabularies Literature primary research articles (~12000) textbooks (~10) protocols (~150) web sites and databases (~50) Community individual database submission (e.g. research interest) collaboration (e.g. JIC, MaizeDB, Gramene) bulk contribution (e.g. Monsanto)