The Vertebrate Genome Annotation (Vega) database

The Vertebrate Genome Annotation (Vega) database (http://vega.sanger.ac.uk) has been designed to be a community resource for browsing manual annotation of finished sequences from a variety of vertebrate genomes. Its core database is based on an Ensembl-style schema, extended to incorporate curation-specific metadata. In collaboration with the genome sequencing centres, Vega attempts to present consistent high-quality annotation of the published human chromosome sequences. In addition, it is also possible to view various finished regions from other vertebrates, including mouse and zebrafish. Vega displays only manually annotated gene structures built using transcriptional evidence, which can be examined in the browser. Attempts have been made to standardize the annotation procedure across each vertebrate genome, which should aid comparative analysis of orthologues across the different finished regions

The vertebrate genome annotation (Vega) database

The Vertebrate Genome Annotation (Vega) database (http://vega.sanger.ac.uk) was first made public in 2004 and has been designed to view manual annotation of human, mouse and zebrafish genomic sequences produced at the Wellcome Trust Sanger Institute. Since its initial release, the number of human annotated loci has more than doubled to close to 33 000 and now contains comprehensive annotation on 20 of the 24 human chromosomes, four whole mouse chromosomes and around 40% of the zebrafish Danio rerio genome. In addition, we offer manual annotation of a number of haplotype regions in mouse and human and regions of comparative interest in pig and dog that are unique to Vega

Update On The Zebrafish Genome Project

The zebrafish genome, which consists of 25 linkage groups and is ~1.4Gb in size, is being sequenced, finished and analysed in its entirety at the Wellcome Trust Sanger Institute. The manual annotation is provided by the Human and Vertebrate Analysis and Annotation (HAVANA) group and is released at regular intervals onto the Vertebrate Genome Annotation (Vega) database ("http://vega.sanger.ac.uk":http://vega.sanger.ac.uk) and may be viewed as a DAS source in Ensembl ("http://www.ensembl.org/Danio_rerio":http://www.ensembl.org/Danio_rerio). 

Our annotation is compiled in close collaboration with the Zebrafish Information Network (ZFIN) ("http://zfin.org/":http://zfin.org/), which has enabled us to provide an accurate, dynamic and distinct resource for the zebrafish community as a whole.

Annotation is based on the reference genome sequence, which is derived from a minimal tile path assembly composed of clones that have been mapped, sequenced and meticulously finished to a sequence accuracy of over 99.9% per 100Kb. We expect to have 90% of the zebrafish genome to a finished standard by the end of 2009. Our approach to annotation uses two strategies. Firstly, the generation and annotation of gene lists comprising of cDNA (8995 in total) found in ZFIN that maps to our current reference assembly. And, secondly, by using clone by clone annotation, where we have annotated over 3200 genes, 1100 transcripts and 130 pseudogenes across 11 linkage groups and 3530 clones. As well as our on-going genome annotation we also welcome external annotation requests for specific genes and regions, which already include the annotation of 93 genes associated with human obesity and the scheduled annotation of the Major Histocompatability Complex, which will utilise reference sequence taken from libraries of a double haploid fish and complement our previous work on the human and mouse MHC already published.
 
External requests and any feedback, questions or requests can be sent to zfish-help [at] sanger.ac.uk

Ensembl 2005

The Ensembl (http://www.ensembl.org/) project provides a comprehensive and integrated source of annotation of large genome sequences. Over the last year the number of genomes available from the Ensembl site has increased by 7 to 16, with the addition of the six vertebrate genomes of chimpanzee, dog, cow, chicken, tetraodon and frog and the insect genome of honeybee. The majority have been annotated automatically using the Ensembl gene build system, showing its flexibility to reliably annotate a wide variety of genomes. With the increased number of vertebrate genomes, the comparative analysis provided to users has been greatly improved, with new website interfaces allowing annotation of different genomes to be directly compared. The Ensembl software system is being increasingly widely reused in different projects showing the benefits of a completely open approach to software development and distribution

Expression of Conjoined Genes: Another Mechanism for Gene Regulation in Eukaryotes

From the ENCODE project, it is realized that almost every base of the entire human genome is transcribed. One class of transcripts resulting from this arises from the conjoined gene, which is formed by combining the exons of two or more distinct (parent) genes lying on the same strand of a chromosome. Only a very limited number of such genes are known, and the definition and terminologies used for them are highly variable in the public databases. In this work, we have computationally identified and manually curated 751 conjoined genes (CGs) in the human genome that are supported by at least one mRNA or EST sequence available in the NCBI database. 353 representative CGs, of which 291 (82%) could be confirmed, were subjected to experimental validation using RT-PCR and sequencing methods. We speculate that these genes are arising out of novel functional requirements and are not merely artifacts of transcription, since more than 70% of them are conserved in other vertebrate genomes. The unique splicing patterns exhibited by CGs reveal their possible roles in protein evolution or gene regulation. Novel CGs, for which no transcript is available, could be identified in 80% of randomly selected potential CG forming regions, indicating that their formation is a routine process. Formation of CGs is not only limited to human, as we have also identified 270 CGs in mouse and 227 in drosophila using our approach. Additionally, we propose a novel mechanism for the formation of CGs. Finally, we developed a database, ConjoinG, which contains detailed information about all the CGs (800 in total) identified in the human genome. In summary, our findings reveal new insights about the functionality of CGs in terms of another possible mechanism for gene regulation and genomic evolution and the mechanism leading to their formation

The Consensus Coding Sequence (Ccds) Project: Identifying a Common Protein-Coding Gene Set for the Human and Mouse Genomes

Effective use of the human and mouse genomes requires reliable identification of genes and their products. Although multiple public resources provide annotation, different methods are used that can result in similar but not identical representation of genes, transcripts, and proteins. The collaborative consensus coding sequence (CCDS) project tracks identical protein annotations on the reference mouse and human genomes with a stable identifier (CCDS ID), and ensures that they are consistently represented on the NCBI, Ensembl, and UCSC Genome Browsers. Importantly, the project coordinates on manually reviewing inconsistent protein annotations between sites, as well as annotations for which new evidence suggests a revision is needed, to progressively converge on a complete protein-coding set for the human and mouse reference genomes, while maintaining a high standard of reliability and biological accuracy. To date, the project has identified 20,159 human and 17,707 mouse consensus coding regions from 17,052 human and 16,893 mouse genes. Three evaluation methods indicate that the entries in the CCDS set are highly likely to represent real proteins, more so than annotations from contributing groups not included in CCDS. The CCDS database thus centralizes the function of identifying well-supported, identically-annotated, protein-coding regions.National Human Genome Research Institute (U.S.) (Grant number 1U54HG004555-01)Wellcome Trust (London, England) (Grant number WT062023)Wellcome Trust (London, England) (Grant number WT077198

Systematic identification of pseudogenes through whole genome expression evidence profiling

The identification of pseudogenes is an integral and significant part of the genome annotation because of their abundance and their impact on the experimental analysis of functional genes. Most of the computational annotation systems are not optimized for systematic pseudogene recognition, often annotating pseudogenes as functional genes, and users then propagate these errors to subsequent analyses and interpretations. In order to validate gene annotations and to identify pseudogenes that are potentially mis-annotated, we developed a novel approach based on whole genome profiling of existing transcript and protein sequences. This method has two important features: (i) equally detects both processed and non-processed pseudogenes and (ii) can identify transcribed pseudogenes. Applying this method to the human Ensembl gene predictions, we discovered that 2011 (9% of total) Ensembl genes in the categories of known and novel might be pseudogenes based on expression evidence. Of these, 1200 genes are found to have no existing evidence of transcription, and 811 genes are found with transcription evidence but contain significant translation disruption. Approximately 40% of the 2011 identified pseudogenes presented a multi-exon structure, representing non-processed pseudogenes. We have demonstrated the power of whole genome profiling of expression sequences to improve the accuracy of gene annotations

The UCSC Genome Browser Database: update 2006

The University of California Santa Cruz Genome Browser Database (GBD) contains sequence and annotation data for the genomes of about a dozen vertebrate species and several major model organisms. Genome annotations typically include assembly data, sequence composition, genes and gene predictions, mRNA and expressed sequence tag evidence, comparative genomics, regulation, expression and variation data. The database is optimized to support fast interactive performance with web tools that provide powerful visualization and querying capabilities for mining the data. The Genome Browser displays a wide variety of annotations at all scales from single nucleotide level up to a full chromosome. The Table Browser provides direct access to the database tables and sequence data, enabling complex queries on genome-wide datasets. The Proteome Browser graphically displays protein properties. The Gene Sorter allows filtering and comparison of genes by several metrics including expression data and several gene properties. BLAT and In Silico PCR search for sequences in entire genomes in seconds. These tools are highly integrated and provide many hyperlinks to other databases and websites. The GBD, browsing tools, downloadable data files and links to documentation and other information can be found at