Confessions/Disclaimers Ontologies and RED fly CARO SO OBO Foundry

1. Confessions/Disclaimers • Ontologies and REDfly • CARO • SO • OBO Foundry

2. CRM minimal promoter green fluorescent protein reporter construct make transgenic animal REDflyRegulatory Element Database for Drosophila Database of known Drosophilacis-regulatory elements • over 675 CRMs so far from >150 genes • includes sequence and expression pattern • includes links to other relevant databases • soon will include transcription factor binding site data (FlyReg) • soon will include images of expression patterns • data exchange with ORegAnno in development

11. Ontologies and REDfly

12. Ontologies andREDfly Our overall goal is to create a comprehensive source of sequence and expression pattern data for Drosophila transcriptional cis-regulatory moduleswithin a completely interoperable, ontology-compliant database framework.This framework can then be used as a model for managing CRM data from any other organism.

13. Ontology: A Vision for the Future and Its Realization The OBO Foundry Barry Smith University at Buffalo http://ontology.buffalo.edu/smith

14. undergoing rigorous reform GO Gene Ontology ChEBI Chemical Ontology CL Cell Ontology FMA Foundational Model of Anatomy PaTO Phenotype Quality Ontology SO Sequence Ontology CARO Common Anatomy Reference Ontology CTO Clinical Trial Ontology FuGO OBI Ontology of Biomedical Investigation PrO Protein Ontology RnaO RNA Ontology RO Relation Ontology new

15. organism/species ontology GO OBI CARO/Drosophila anatomy ontology SO Ontologies andREDfly CRM type (promoter, silencer, etc.)

16. Ontologies and REDfly: anatomy

17. Ontologies and REDfly: anatomy

18. Ontologies and REDfly: GO

19. Ontologies and REDfly: GO

20. mus musculus evx1 central nervous system Ontologies and REDfly: complex queries

21. CARO: Common Anatomy Reference Ontology

22. CARO: Common Anatomy Reference Ontology http://www.bioontology.org/wiki/index.php/CARO:Main_Page The main focus of this workshop is to pave the way for interoperability between the anatomical ontologies developed for various organisms (including human) by agreeing on shared methodologies for building our respective ontologies. 1. a list of relations (especially part_of) used within anatomical anatomies, including definitions and rules for consistent use within anatomy ontologies; 2. a list of major organizational units of biological organisms at all levels of granular partitions (e.g. biological macromolecule, cell, organ); 3. a representation of developmental stages of organisms; are anatomy and development two separate or one single integrated ontology? If separate what are the relations between them and how should they be applied; 4. a method that allows automated reasoners to recognize homologous anatomical structures of different species. In order to meet our objectives, we need to create a common anatomy reference ontology (CARO) designed to ensure interoperability of the anatomy ontologies developed for specific organisms. This common ontology will comprehend both top-level categories and a common set of relations to be used within anatomical ontologies; CARO will be embedded in a set of principles for constructing anatomy ontologies for different organisms at different developmental stages.

23. CARO: Common Anatomy Reference Ontology http://www.bioontology.org/wiki/index.php/CARO:Main_Page

24. CARO: Common Anatomy Reference Ontology http://www.bioontology.org/wiki/index.php/CARO:Main_Page Committed or likely to commit: zebrafish (ZFIN) Drosophila (FlyBase) human (FMA) amphibians cyprinoforme fishes hymenoptera (bees, wasps, ants) mouse (MGI) Dictyostelium (dictyBase) C. elegans (WormBase)

25. SO: Sequence Ontology

26. SO: Sequence Ontology http://www.sequenceontology.org The Sequence Ontology is a set of terms and relationships used to describe the features and attributes of biological sequence. It encompasses both "raw" features, such as nucleotide similarity hits, and interpretations such as gene models. It also provides a rich set of attributes to describe these features such as "polycistronic" and "maternally imprinted". REDfly: CRM, TFBS ORegAnno: Regulatory haplotype, regulatory polymorphism, regulatory region, TFBS

27. SO: Sequence Ontology http://www.sequenceontology.org REDfly: CRM, TFBS ORegAnno: Regulatory haplotype, regulatory polymorphism, regulatory region, TFBS Obi asks:Discussion item: Should further sub-categorization of regulatory regions be allowed (e.g. Silencer, enhancer, locus-control region, etc) I say: not only “should” but need to be present

28. A cis-acting sequence that increases the utilization of (some) eukaryotic promoters, and can function in either orientation and in any location (upstream or downstream) relative to the promoter. A region of a molecule that binds to a transcription factor. A regulatory_region where more than 1 TF_binding_site together are regulatorily active. Synonyms: CRM SO: Some problems

29. is_a TF_module A regulatory_region where more than 1 TF_binding_site together are regulatorily active. Synonyms: CRM enhancer SO: Some problems

30. The region on a DNA molecule involved in RNA polymerase binding to initiate transcription. A region of sequence which is part of a promotor. partial listing of known core promoter motifs SO: More problems?

31. is_a TF_module? Combination of short DNA sequence elements which suppress the transcription of an adjacent gene or genes. short DNA sequence elements “sequence elements” not defined in ontology A regulatory_region where more than 1 TF_binding_site together are regulatorily active. Synonyms: CRM silencer SO: More problems?

32. is_a TF_module A TF_module that regulates the activity of more than one gene within a defined locus LCR SO: Some problems A DNA region that includes DNAse hypersensitive sites located 5' to a gene that confers the high-level, position-independent, and copy number-dependent expression to that gene.

33. What terms are required to adequately capture cis-regulatory information? CRM_part? “Composite_CRM” ? Yuh and Davidson (1998) Please provide suggestions/examples/cases to me (mshalfon@buffalo.edu), the RegCreative Wiki, or via the SO mailing list (https://lists.sourceforge.net/lists/listinfo/song-devel)

34. What terms are required to adequately capture cis-regulatory information? What additional terms & definitions do we need to add and what needs to be changed? Please provide suggestions/examples/cases to me (mshalfon@buffalo.edu), the RegCreative Wiki, or the SO mailing list (https://lists.sourceforge.net/lists/listinfo/song-devel)