Presentation is loading. Please wait.

Presentation is loading. Please wait.

The Consensus CoDing Sequence (CCDS) Database

Similar presentations

Presentation on theme: "The Consensus CoDing Sequence (CCDS) Database"— Presentation transcript:

1 The Consensus CoDing Sequence (CCDS) Database
Kim D. Pruitt Mouse Genome Annotation Summit Meeting March 12-13, 2008

2 Why is the CCDS project needed?
The Problem: Annotation of the genome sequence is essential – but beware of different interpretations! The availability of the human and mouse genome sequence has had a significant impact on disease and health research. Most scientists rely on annotation information when designing, interpreting, and evaluating research results. Inconsistencies in annotation results among the main public resources hampers use of this important data. Researchers may not realize that a different annotation result is available elsewhere – possibly leading to erroneous or incomplete interpretations.

3 CCDS - A collaborative project
Initiated by the main public annotation/browser groups to address concerns by the scientific community about inconsistencies in the human and mouse genome annotation. Built by consensus among the collaborating members, which include: European Bioinformatics Institute (EBI) National Center for Biotechnology Information (NCBI) University of California, Santa Cruz (UCSC) Sanger Institute (WTSI)

4 What is the CCDS project?
Project Goals identify a core set of protein-coding genes that are consistently annotated and of high quality support convergence toward a standard set of gene annotations Scope: Human and mouse protein coding regions Update frequency Variable Depends on frequency of genome annotation updates

5 Process flow – calculating updates
NCBI (computational) Havana (manual) Ensembl (computational) RefSeq (manual) Compare CDS (Annotation + Sequence) Ensembl merged annotation QA Identical Similar Novel Existing CCDS Retain Lost New match New CCDS ID Out of scope

6 Quality assessment tests include:
Assessing Quality CCDS status is conservatively applied: Annotated CDS coordinates are identical Annotation is of high quality and passes QA tests, or curator review Existing CCDS proteins can be flagged for review by the collaborating members Updates and removals are by consensus agreement. Quality assessment tests include: Consensus splice sites ("GY..AG" or "AT..AC") Valid start and stop codons with no internal stops NMD Low complexity Repeat-containing Insufficient protein homology Genome conservation Putative pseudogene QA test results are reviewed by curators Over-rides are set to retain supported CDSs

7 CCDS Counts Date Build CDS IDs GeneIDs Mar-05 Hs35.1 14,795 13,142 Feb-07 Hs36.2 18,290 16,008 Oct-06 Mm36.1 13,374 13,014 Nov-07 Mm37.1 17,707 16,893 Step Source Genes Proteins Annotation NCBI Annotation Ensembl Matching CDS QA & curation rejections Accepted rejections Final CCDS ID

8 Curation – how are updates curated and coordinated?
Any member of the collaboration can flag a CCDS for review Update the CDS definition (alter N-terminus extent internal splice site) Withdraw the CCDS ID (insufficiently supported, or non-protein coding) NCBI provides a collaboration web site to coordinate this review All collaborators must agree with a change to finalize a decision Withdrawal of a CCDS may happen between genome annotation updates An update to a CCDS is indicated by: Status change: a status of ‘pending update’ is reported when there is collaborative agreement that a change is needed Version change: The CCDS version number is incremented once the change is reflected in public annotation. This only occurs after a genome annotation update and CCDS analysis has taken place. CCDS curation is fully integrated with RefSeq curation

9 CCDS update & curation stats
Curation-based changes: Mouse: ~5200 curated CCDS genes name action status count human update pending human update agreed human withdraw pending human withdraw agreed mouse update pending mouse update agreed mouse withdraw pending mouse withdraw agreed 923 709 242 24 Annotation pipeline-based changes: name build status count human 35.1 Withdrawn, inconsistent annotation human 36.2 Withdrawn, inconsistent annotation mouse 36.1 Withdrawn, inconsistent annotation mouse 37.1 Withdrawn, inconsistent annotation

10 Curation considerations
Alignments Track low quality sequences (‘kill list’) Protein conservation Publications Personal communications QA measures

11 Access – How do I know if an annotation has a CCDS ID?
Genome browser displays NCBI UCSC Gene reports Ensembl Vega Other: RefSeq annotation (NCBI) CCDS web site FTP

12 NCBI Map Viewer (chr.5) Link to CCDS Browser

13 UCSC Browser chr5:

14 UCSC Browser – Tyms gene
CCDS Browser

15 Access of CCDS data at NCBI
CCDS Database & Browser interface Project Description Query support Reports attributes of the CCDS Location data Sequence members Status FTP reports

16 CCDS Browser History Find all CCDSs for the Gene Entrez Gene
View CCDS Details

17 CCDS Browser Mouse-over highlights codon
Click to highlight codon and corresponding amino acid

18 Biology is complex – some CCDS curation examples
1 vs 2 vs ‘n’ genes translation start site

19 1 vs. 2 vs. ‘n’ genes Curation Considerations: Nomenclature
History (scientific use, publications, etc.) Different (but similar) products vs. distinct products Shared promoters

20 carnitine palmitoyltransferase 1b,
choline kinase beta

21 Current RefSeq representation of the region - two protein coding loci
1 vs. 2 vs. ‘n’ genes Current RefSeq representation of the region - two protein coding loci - one non-coding loci for the non-coding transcript product (a read-through transcript) Chkb (CCDS ) Cpt1b (CCDS ) Chkb-cpt1b (PMID: )

22 Translation start site
Curation Considerations Publication reports (CDS begins at ‘n’) Other cDNA sequencing reveals the ORF can be extended further upstream Evaluate: Genome conservation Literature reports for the protein Putative Kozak signals Presence of in-frame upstream stop codon INSDC submissions from an experimental lab source that do have the longer ORF extent annotated. Consult with an expert

23 Internal CCDS browser (restricted access)
Jmjd2d jumonji domain containing 2D (chr 19)

24 Update is agreed on by all parties
Resulting in a 258 aa N-terminal extension

25 Examples – no CCDS ID EBI+WTSI and NCBI transcript annotation may differ even though the gene includes annotations with CCDS IDs

26 Examples –no CCDS ID Reasons: not found by one group
different CDS length different splice sites different internal exon Curation removal EBI/WTSI NCBI EBI/WTSI NCBI EBI/WTSI NCBI EBI/WTSI NCBI

27 Acknowledgements Collaborators at Ensembl, UCSC, Vega Donna Maglott
Josh Cherry Keith Oxenride Craig Wallin Andrei Shkeda RefSeq Curators NCBI Genome Annotation Group NCBI Map Viewer Group Collaborators at Ensembl, UCSC, Vega Jen Ashurst & Vega curator group Rachel Harte Mark Diekhans Steve Searle

28 Ensembl – Tyms gene

29 Vega browser Tyms gene (chromosome 5 30388989-30404404)

Download ppt "The Consensus CoDing Sequence (CCDS) Database"

Similar presentations

Ads by Google