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Exploring Sequence Ontology (SO) in Genome Annotation and Genomic Analysis

Learn about Sequence Ontology, its role in describing biological sequences, genome annotations, and genomic analysis. Discover how SO is used, managed, and its significance in genomics data standardization. Explore SO's application in Model Organism Databases, NLP, and Comparative Genomics.

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Exploring Sequence Ontology (SO) in Genome Annotation and Genomic Analysis

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  1. SO meets RNAO Karen Eilbeck University of Utah RNAO Consortium Meeting May 28-29 2007

  2. What SO is. • How SO is used • How SO is managed • Where do SO and RNAO meet • How SO and RNAO can work together • If we have time - a demo of OBO-Edit

  3. The Sequence Ontology describes the features of biological sequence • Genome sequence • Annotation of regions • Coordinates • Need to agree on meaning of terms. E.g. Does the CDS include the stop codon?

  4. An annotation captures what we know about a gene 3 Alternate transcripts of Glut1 gene evidence Annotations Start codon 5’ UTR Coding exon Transposon within intron

  5. d i i i i i i i i i i P P P P P P P P Structure of the ontology exon transcript • SO is structured into a directed acyclic graph. intron processed transcript polyA site primary transcript clip splice site protein coding primary transcript nc primary transcript CDS ncRNA mRNA UTR tRNA rRNA five_prime_UTR three_prime_UTR

  6. GFF3 • SO is used to ‘type’ the features and relationships. Id type start end strand attributes ctg123 . gene 1000 9000 . + . ID=gene00001;Name=EDEN ctg123 . TF_binding_site 1000 1012 . + . ID=tfbs00001;Parent=gene00001 ctg123 . mRNA 1050 9000 . + . ID=mRNA00001;Parent=gene00001;Name=EDEN.1 ctg123 . mRNA 1050 9000 . + . ID=mRNA00002;Parent=gene00001;Name=EDEN.2 ctg123 . mRNA 1300 9000 . + . ID=mRNA00003;Parent=gene00001;Name=EDEN.3 ctg123 . exon 1300 1500 . + . ID=exon00001;Parent=mRNA00003 ctg123 . exon 1050 1500 . + . ID=exon00002;Parent=mRNA00001,mRNA00002 ctg123 . exon 3000 3902 . + . ID=exon00003;Parent=mRNA00001,mRNA00003 ctg123 . exon 5000 5500 . + . ID=exon00004;Parent=mRNA00001,mRNA00002,mRNA00003 ctg123 . exon 7000 9000 . + . ID=exon00005;Parent=mRNA00001,mRNA00002,mRNA00003 terms relationships

  7. Why we made SO • Standardize vocabulary used in genomics. • Clarify the relationships between the terms. • Make genomics data more computable by adding semantics to the sequence. Its not just about sequence similarity.

  8. What is the scope of SO? • Features that can be located on a sequence with coordinates. exon, promoter, binding_site • Properties of these features: • Sequence attributes • Maternally_imprinted • Consequences of mutation • mutation_affecting_editing • Chromosome variation • aneuploid

  9. Model Organism DB SGD (MGI) FlyBase WormBase DictyBase Pombe GMOD Comparative genomics MGED Ontology NLP The SO community

  10. Genome annotation unification • The model organism databases use SO to type their features. • The GFF3 file format for annotation, the Chado db schema and DAS2 annotation protocol rely on SO to type features.

  11. Genomic analysis • The Comparative Genomics Library written in Perl uses SO based annotations to perform complex analysis over multiple genomes. • Yandell M, Mungall CJ, Smith C, Prochnik S, Kaminker J, Hartzell G, Lewis S, Rubin GM. 2006. Large-Scale Trends in the Evolution of Gene Structures within 11 Animal Genomes. PLoS Comput Biol. 2:e15

  12. Genome data integration • Multiple genomes are organized using SO: • Flymine, • Gramene, • the BRCs

  13. NLP/text mining • Recently SO have been used for some new projects - • Semantic enrichment by the Royal Society of Chemistry. • Anaphora resolution by the NLIP group in Cambridge.

  14. How SO is managed • SO uses CVS to manage and version the ontology. • There is a mailing list for developers to get things off their chest. • There is a tracker for term suggestions • There are workshops when we get a critical mass for a given problem. We want to do more workshops. • SO is expressed in OBO format.

  15. Example of OBO format • http://www.geneontology.org/GO.format.obo-1_2.shtml [Term] id: SO:0000587 name: group_I_intron def: "Group I catalytic introns are large self-splicing ribozymes. They catalyse their own excision from mRNA, tRNA and rRNA precursors in a wide range of organisms. The core secondary structure consists of 9 paired regions (P1-P9). These fold to essentially two domains, the P4-P6 domain (formed from the stacking of P5, P4, P6 and P6a helices) and the P3-P9 domain (formed from the P8, P3, P7 and P9 helices). Group I catalytic introns often have long ORFs inserted in loop regions." [http://www.sanger.ac.uk/cgi-bin/Rfam/getacc?RF00028] subset: SOFA is_a: SO:0000188 ! intron

  16. OBO and OWL • http://purl.org/obo/owl/SO • Mapping OBO and OWL http://www.bioontology.org/wiki/index.php/OboInOwl:Main_Page

  17. Navigate SO using OBO-Edit Search the ontology Details for selected term Structure of the ontology All parents of the term

  18. AGAGGGCGAATCCAGCTCTGGAGCAGAGGCTCTGGCAGCTTTTGCAGCGTTTATATAACATGAAATATATATACGCATTCCGATCAAAGCTGGGTTAACCAGATAGATAGATAGTAACGTTTAAATAGCGCCTGGCGCGTTCGATTTTAAAGAGATTTAGAGCGTTATCCCGTGCCTATAGATCTTATAGTATAGACAACGAACGATCACTCAAATCCAAGTCAATAATTCAAGAATTTATGTCTGTTTCTGTGAAAGGGAAACTAATTTTGTTAAAGAAGACTTACAATATCGTAATACTTGTTCAATCGTCGTGGCCGATAGAAATATCTTACAATCCGAAAGTTGATGAATGGAATTGGTCTGCAACTGGTCGCCTTCATTTCGTAAAATGTTCGCTTGCGGCCGAAAAATTTCGATATATCTACAATTGATCTACAATCTTTACTAAATTTTGAAAAAGGAACACTTTGAATTTCGAACTGTCAATCGTATCATTAGAATTTAATCTAAATTTAAATCTTGCTAAAGGAAATAGCAAGGAACACTTTCGTCGTCGGCTACGCATTCATTGTAAAATTTTAAATTTTGACATTCCGCACTTTTTGATAGATAAGCGAAGAGTATTTTTATTACATGTATCGCAAGTATTCATTTCAACACACATATCTATATATATATATATATATATATATATATATATATATATATATGTTATATATTTATTCAATTTTGTTTACCATTGATCAATTTTTCACACATGAAACAACCGCCAGCATTATATAATTTTTTTATTTTTTTAAAAAATGTGTACACATATTCTGAAAATGAAAAATTCAATGGCTCGAGTGCCAAATAAAGAAATGGTTACAATTTAAGGAGAGGGCGAATCCAGCTCTGGAGCAGAGGCTCTGGCAGCTTTTGCAGCGTTTATATAACATGAAATATATATACGCATTCCGATCAAAGCTGGGTTAACCAGATAGATAGATAGTAACGTTTAAATAGCGCCTGGCGCGTTCGATTTTAAAGAGATTTAGAGCGTTATCCCGTGCCTATAGATCTTATAGTATAGACAACGAACGATCACTCAAATCCAAGTCAATAATTCAAGAATTTATGTCTGTTTCTGTGAAAGGGAAACTAATTTTGTTAAAGAAGACTTACAATATCGTAATACTTGTTCAATCGTCGTGGCCGATAGAAATATCTTACAATCCGAAAGTTGATGAATGGAATTGGTCTGCAACTGGTCGCCTTCATTTCGTAAAATGTTCGCTTGCGGCCGAAAAATTTCGATATATCTACAATTGATCTACAATCTTTACTAAATTTTGAAAAAGGAACACTTTGAATTTCGAACTGTCAATCGTATCATTAGAATTTAATCTAAATTTAAATCTTGCTAAAGGAAATAGCAAGGAACACTTTCGTCGTCGGCTACGCATTCATTGTAAAATTTTAAATTTTGACATTCCGCACTTTTTGATAGATAAGCGAAGAGTATTTTTATTACATGTATCGCAAGTATTCATTTCAACACACATATCTATATATATATATATATATATATATATATATATATATATATATGTTATATATTTATTCAATTTTGTTTACCATTGATCAATTTTTCACACATGAAACAACCGCCAGCATTATATAATTTTTTTATTTTTTTAAAAAATGTGTACACATATTCTGAAAATGAAAAATTCAATGGCTCGAGTGCCAAATAAAGAAATGGTTACAATTTAAGG Annotating with SO and RNAO Translational control element The nanos translational control element represses translation in somatic cells by a Bearded box-like motif.･Duchow HK, Brechbiel JL, Chatterjee S, Gavis ER. Developmental Biology Volume 282, Issue 1, 1 June 2005, Pages 207-217

  19. Overlap with RNAO • SO provides regions of sequence - start and stop coordinates with regards to the whole sequence - i.e. assembly / chromosome • Transcripts and parts of transcripts • Some secondary structure • Some motifs • Results of algorithms such as blast

  20. SO names features

  21. Secondary structure • This part of SO needs work. • Any volunteers?

  22. Divergent from RNAO • Where do SO and RNAO differ dramatically? • Multiple sequence alignments. SO does not provide a solution to this. It does however provide the terms to describe the results of sequence similarity searches. • Numerical results. SO has not needed to use values so far.

  23. RNAO working groups • Motif identification/annotation • RNA interaction • Biochemical-structuremapping • Multiple sequence alignment • Backbone conformation • Base stacking

  24. Working together • Remain 2 separate ontologies. • Give SO annotators option of ‘importing’ RNAO terms using the OBO programs • SO and RNAO work together to align key terms in their ontologies.

  25. SO is still evolving • RNAO could use the SO features to describe regions of sequence • SO could reference RNAO for detailed annotation of structure and biochemical features.

  26. Multiple ontologies in OBO • 2 options. • The ontologies reference each other: • Will always need to load both ontologies • There is a mapping file that you can load to import external terms. • Maintain separate ontologies and keep mapping up to date. http://obofoundry.org/wiki/index.php/Mappings

  27. Example: Importing terms from SCOR. • 1. Made an OBO file from a subset of SCOR terms • 2. Work out where there is overlap • 3. Make OBO mapping file between the two ontologies • 4. Load all 3 files at once.

  28. format-version: 1.2 date: 16:05:2007 15:26 saved-by: kareneilbeck auto-generated-by: OBO-Edit 1.100 [Term] id: SC:0000000 name: hairpin_loop [Term] id: SC:0000001 name: diloop is_a: SC:0000000 ! hairpin_loop [Term] id: SC:0000002 name: triloop is_a: SC:0000000 ! hairpin_loop … format-version: 1.2 date: 24:05:2007 10:37 saved-by: kareneilbeck import: so-xp.obo import: scor2.obo id: SC:0000015 hairpin loop is_a: SO:0000715 is_a RNA motif id: SC:0000016 internal loop is_a: SO:0000715 is_a RNA motif id: SC:0000035 tertiary interaction is_a: SO:0000122 is_a RNA sequence secondary structure scor.obo mapping file

  29. OBO-Edit DEMO • Fingers crossed…

  30. Possible action items • A SO-RNAO mailing list for discussion of collaboration • Phone/skype/webinars at intervals to keep track of progress.

  31. Resources • GFF3 http://www.sequenceontology.org/gff3.shtml • Apollo http://www.fruitfly.org/annot/apollo/ • SO http://www.sequenceontology.org • OBO-Edit http://sourceforge.net/projects/geneontology • OBO foundry http://www.obofoundry.org • GO-perl http://www.godatabase.org/dev/go-perl/doc/go-perl-doc.html

  32. Acknowledgements • SO is funded as part fo the Gene Ontology Consortium, via the NIH P41-HG002274 • People: • Suzi Lewis and Michael Ashburner - the vision • Chris Mungall - programming infrastructure • John Richter - made OBO-Edit

  33. keilbeck@genetics.utah.edu

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