The objective of the GENCODE consortium is to create a foundational reference genome annotation, in which all gene features in the human and mouse genomes are identified and classified with high accuracy based on biological evidence, and then to release these annotations for the benefit of biomedical research and genome interpretation. GENCODE aims for a better understanding of a `normal' human genome; using genome sequences of the most commonly used mouse strains will facilitate the most effective use of these key models for large-scale knockout analysis and disease-specific research. To produce regular annotation releases of high accuracy, GENCODE will continue to follow its well-established and conservative research design, supplemented by targeted investigations into the value of new technologies, new data and new sources of evidence. GENCODE focuses on protein-coding and non-coding loci, including their alternatively spliced isoforms and pseudogenes. Over the course of this proposal GENCODE will follow major directions in genomics, including graph- based genome representations, long-read transcriptome sequencing, connecting genes and the associated regulatory regions that affect their transcription, and identifying genes that are not present on the current reference assembly. The GENCODE consortium has four fundamental components: (1) a comprehensive gene annotation pipeline leveraging manual annotation; (2) an integrated approach to pseudogene identification and classification; (3) a set of computational methods to evaluate and enhance gene annotation; and (4) complementary experimental pipelines for validation and functional annotation. More specifically, in the next four years GENCODE aims to (1) extend the human and mouse GENCODE gene sets to as near completion as possible given current experimental technology; (2) deploy population-based genome annotation to ensure that any transcript isoform expressed in an individual human will be present in the reference annotation set; (3) extend the gene annotation to include core regulatory regions and tissue-specific enhancers from selected datasets; (4) to distribute GENCODE annotations and engage with community annotation efforts. Current popular distribution channels for GENCODE data including the GENCODE web site, the Ensembl and UCSC Genome Browsers, will be maintained. Finally, new mechanisms for prioritizing genes for manual annotation with community input will be established, with the long-term aim of establishing GENCODE as the standard annotation set for research and clinical genomics efforts.

Public Health Relevance

The GENCODE project produces reference gene annotation for the human and mouse genomes. The annotation provides a reference from which to conduct clinical and genomics research in the short term; in the long term it informs all research that will contribute fundamental knowledge to benefit public health.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Biotechnology Resource Cooperative Agreements (U41)
Project #
2U41HG007234-05
Application #
9277658
Study Section
Special Emphasis Panel (ZHG1)
Program Officer
Gilchrist, Daniel A
Project Start
2013-04-01
Project End
2021-05-31
Budget Start
2017-08-01
Budget End
2018-05-31
Support Year
5
Fiscal Year
2017
Total Cost
Indirect Cost
Name
European Molecular Biology Laboratory
Department
Type
DUNS #
321691735
City
Heidelberg
State
Country
Germany
Zip Code
69117
Tress, Michael L; Abascal, Federico; Valencia, Alfonso (2017) Most Alternative Isoforms Are Not Functionally Important. Trends Biochem Sci 42:408-410
Tress, Michael L; Abascal, Federico; Valencia, Alfonso (2017) Alternative Splicing May Not Be the Key to Proteome Complexity. Trends Biochem Sci 42:98-110
Ruffier, Magali; Kähäri, Andreas; Komorowska, Monika et al. (2017) Ensembl core software resources: storage and programmatic access for DNA sequence and genome annotation. Database (Oxford) 2017:
Steward, Charles A; Parker, Alasdair P J; Minassian, Berge A et al. (2017) Genome annotation for clinical genomic diagnostics: strengths and weaknesses. Genome Med 9:49
Schlaffner, Christoph N; Pirklbauer, Georg J; Bender, Andreas et al. (2017) Fast, Quantitative and Variant Enabled Mapping of Peptides to Genomes. Cell Syst 5:152-156.e4
Lagarde, Julien; Uszczynska-Ratajczak, Barbara; Carbonell, Silvia et al. (2017) High-throughput annotation of full-length long noncoding RNAs with capture long-read sequencing. Nat Genet 49:1731-1740
Aken, Bronwen L; Achuthan, Premanand; Akanni, Wasiu et al. (2017) Ensembl 2017. Nucleic Acids Res 45:D635-D642
Breschi, Alessandra; Djebali, Sarah; Gillis, Jesse et al. (2016) Gene-specific patterns of expression variation across organs and species. Genome Biol 17:151
Zerbino, Daniel R; Johnson, Nathan; Juetteman, Thomas et al. (2016) Ensembl regulation resources. Database (Oxford) 2016:
Wright, James C; Mudge, Jonathan; Weisser, Hendrik et al. (2016) Improving GENCODE reference gene annotation using a high-stringency proteogenomics workflow. Nat Commun 7:11778

Showing the most recent 10 out of 69 publications