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Annotator Interface

Annotator Interface. Sharon Diskin GUS 3.0 Workshop June 18-21, 2002. Outline. Current annotation efforts Motivation for new annotation tool Requirements for new annotation tool Thoughts on design and implementation Future plans. Current Annotation Efforts. Overview of Current Efforts.

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Annotator Interface

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  1. Annotator Interface Sharon Diskin GUS 3.0 Workshop June 18-21, 2002

  2. Outline • Current annotation efforts • Motivation for new annotation tool • Requirements for new annotation tool • Thoughts on design and implementation • Future plans

  3. Current Annotation Efforts

  4. Overview of Current Efforts • Automated annotation has been applied to the DoTS transcripts • Predicted gene ownership (clustering of assemblies) • BlastX against NR • Automated assignment of descriptions based on similarity • BlastX against ProDom and RPS-Blast against CDD • Predicted GO Functions • Framefinder • Predicted Protein Sequences • Blat alignments • EPCR, Index Words, etc… • Manual annotation efforts have focused on • validating the automated annotation and • adding additional information at the central dogma level • Manual annotation of the gene index utilizes an annotation tool, the GUS Annotator Interface, which directly updates the GUSdev database.

  5. DoTS RNA transcripts Incoming Sequences (EST/mRNA) • GenBank, dbEST sequences • Make Quality (remove vector, polyA, NNNs) The assembly of sequences generates a consensus sequence or DoTS transcript “Quality” sequences • Block with RepeatMasker Blocked sequences • Blastn to cluster sequences “Unassembled” clusters • Assemble sequences with CAP4 CAP4 assemblies (generate consensus sequences) BLASTn DoTs consensus sequences (98% identity, 150bps) Gene Cluster (RNA s in the Gene) Dots Consensus sequences

  6. Assembly_1 Instance_1 Feature_1 RNA_1 Assembly_2 Instance_2 Feature_2 RNA_2 Assembly_3 Instance_3 Feature_3 RNA_3 Assembly_4 Instance_4 Feature_4 RNA_4 Assembly_5 Instance_5 Feature_5 RNA_5 Current Efforts: Gene Annotation (1) Gene RNA RNAInstance RNAFeature Assembly Generate DoTS transcripts Gene_A … … … … Task 1: Validation of Gene Membership

  7. Assembly_1 Instance_1 Feature_1 Assembly_2 Instance_2 Feature_2 Assembly_3 Instance_3 Feature_3 Assembly_4 Instance_4 Feature_4 Assembly_5 Instance_5 Feature_5 Current Efforts: Gene Annotation (2) Gene RNA RNAInstance RNAFeature Assembly Generate DoTS transcripts RNA_1 Gene_A RNA_2 RNA_3 Gene_B RNA_4 … … … RNA_5 • - Removing RNAs from the cluster results in the creation of a new Gene • An entry is made in the MergeSplit table for tracking purposes • Similar process followed when an RNA is added to a Gene

  8. Current Efforts: Gene Annotation (3) Task 2: Assign Reference RNA • will be annotated further • RNA table • Task 3: Assign Approved Gene Name/Symbol • Gene Table • Evidence: Comment (specifies database link) • Task 4: Assign Gene Description • Gene Table • Evidence: Comment • Task 4: Associate known Gene synonyms • GeneSynonym table • Evidence: Comment

  9. Current Efforts: RNA Annotation Annotation of “Reference Sequence” • Task 1: Assign/Confirm Description of assembly • RNA table • Task 2: Confirm/Add/Delete GO Functions • ProteinGOFunction (in GUSdev, GO tables have been re-designed in GUS3.0) • Evidence: Comments or Similarity (ProDom, CDD-Pfam, CDD-Smart, or NR)

  10. Current Annotator Interface Architecture Erebus Zeus Annotator Interface JDBC (Query Only) GUSdev JavaServlet writes executes “XML” file Perl Object Layer DBI(Insert/Update/Delete) reads AnnotatorInterface Submitter GA-Plugin

  11. Current Annotator Interface

  12. Current Gene Annotation Validate Cluster and Assign Reference RNA/Assembly

  13. Current Gene Annotation (cont.) Assign Gene Name/Symbol Assign Gene Description Assign Gene Synonym(s) Evidence

  14. Current RNA (and Protein) Annotation RNA Description Evidence GOFunctions

  15. Allgenes Display of Gene Annotation

  16. Allgenes Display of RNA Annotation RNA Description (Confirmed or manually added GO Functions)

  17. Status of Current Annotation(as of June 20, 2002) • 1289 manually reviewed genes • 1003 with gene name • 697 with gene synonyms • 1046 with description • 6146 manually reviewed RNAs/DoTS assemblies • 949 ‘proteins’ with reviewed GO function

  18. Motivation for new tool Want to annotate using genomic sequence • Create “curated” gene models specifying structure • Increase structure of annotation in GUS • Annotation of proteins • Redefinition of annotation tasks • Current interface not designed for this purpose

  19. Some Other Annotation Tools • Artemis • Developed and used at Sanger • Reads and writes flat files • Supports rich set of annotations • Save as EMBL format • Apollo • Combined effort including members from Sanger and Berkeley • Flat files (CORBA access to ENSEMBL) • 2 versions, currently being merged • Sanger: annotation viewer • Berkeley: focus on editing No Existing Tool To Meet All of Our Needs

  20. Requirements At a High Level

  21. Requirements: Graphical View • Provide alignment of features on genomic sequence • could potentially display any feature type currently stored in GUS3.0 • features can be selected and used to generate “curated” features • similar to display and functionality in Apollo • Toggle (or configure) the display of each feature type • Zoom to sequence level and will include links to functionality relevant to the feature highlighted • Also support creation of features “from scratch” • based on literature, etc. • Detail editors provide ability to change endpoints, etc.

  22. Gene Annotation • Create curated gene model • specify gene boundaries • specify location of exons (and thus introns) • 5' exon boundary (putative transcription start site) • 3' exon boundary (include poly adenylation signal) • automatic creation of Gene entry • merge with existing gene instances through GeneInstance table • tables/views affected: • GeneFeature • ExonFeature • GeneInstance • Gene • MergeSplit • evidence: features used to create model, PubMed ID • should be as easy as clicking on existing features and saying make curated (then can modify endpoints, etc. if needed)

  23. Gene Annotation (2) • Assign (HUGO or MGI approved) abbrievated gene name/symbol • Gene Table • Evidence: ExternalDatabaseLink • Assign full gene name (MGI or HUGO full gene name) • Gene Table • Evidence: ExternalDatabaseLink • Assign abbrievated gene name/symbol synonyms (non-approved gene symbols) • GeneSynonym Table • Evidence: ExternalDatabaseLink • Assign full gene name aliases • GeneAlias Table • Evidence: ExternalDatabaseLink

  24. Gene Annotation (3) • Assign gene category (e.g. non-coding) • Gene Table • Evidence: • ExternalDatabaseLink/Literature Reference • Similarity (eg. to known non-coding RNA) • Confirm/assign gene chromosomal location • GeneChromosomalLocation • Evidence: • ExternalDatabaseLink/Literature Reference • RH mapping data • Alignments/Features • OMIM Link assignment (verification if computationally determined) • ExternalDatabaseLink

  25. RNA Annotation (1) • Create “curated RNAs” • Define RNA transcript forms of gene (create RNAs) • Using exons defined by curated gene • 5' and 3' UTRs • Automatic creation of RNA entry • Merge existing RNA instances • Tables affected: • RNAFeature • UTRFeature • RNAInstance • RNA • Evidence: Features used to create • Assign RNA categories to created RNAs (e.g. alternative form) • RNARNACategory Table

  26. RNA Annotation • Assign (or confirm computed) RNA description • RNA table • Evidence: Gene from which it is derived • Anatomy expression assignment(s) • RNAAnatomy • RNAAnatomyLOE • Evidence: • ExternalDatabaseLink/Literature references • Assembly anatomy percent from DoTS • RAD experiments • Assign GO terms to curated RNA (non-coding RNAs, e.g. small RNA involved in splicing) • GOTermAssociation • GOTermAssociationEvid • Evidence: ExternalDatabaseLInk, Literature References • Computational analysis performed on curated RNA sequences • Annotation workflow • Framefinder translation, GO terms, Similarities, etc.

  27. Requirements: Protein Annotation • Confirm/assign GO Function • GOTermAssociation, GOTermAssociationEvid • Evidence: ExternalDatabaseLink and/or Literature References • Confirm/assign GO Biological Process • GOTermAssociation, GOTermAssociationEvid • Evidence: ExternalDatabaseLink and/or Literature References • Confirm/assign GO Cellular Component • GOTermAssociation, GOTermAssociationEvid • Evidence: ExternalDatabaseLink and/or Literature References • Assign protein name • Protein Table • Evidence: ExternalDatabaseLink, Literature Ref, Similarities • Assign protein name synonyms • Protein Table • Evidence: ExternalDatabaseLink, Literature Ref, Similarities

  28. Protein Annotation (2) • Assign protein category (post-translational modifications) • ProteinProteinCategory • Evidence: ExternalDatabaseLink, Literature References • Protein-protein interactions assigned • Interaction • InteractionInteractionLOE • Evidence: PubMed ID, etc. • Protein pathway assignments • PathwayInteraction (for newly created interactions) • Still under consideration: What is best way to link with existing pathway • for example, Pathway is represented in DoTS, and we want to say that this curated Protein is really the same as a protein in a pathway. • Assign post translational modification category • Assign interactions involving this protein • Assign pathway protein is known to be involved in • Assign protein family • Ability to modify and/or delete curated protein Evidence will be associated with all annotation

  29. Next Steps/ Open Issues • Completion of Java Object Layer • Decision regarding BioJava wrappers • What exactly will this give us to aid in interface development (eg. FeatureRenderer, etc…) • Discussion on layout of interface • Joan’s input after experimentation with other tools • Depending on the above : • Client Side portion which communicates with remote GUS Server • Interface Implementation

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