Transcript Slide 1
The Ensembl Browser Dr. Giulietta M. Spudich European Bioinformatics Institute 1 of 31 Today Introduction to the Ensembl project and gene set Walk-through of the browser Hands-on Browser BioMart Lunch BioMart Hands-on Comparative Genomics + Hands-on Variations &Functional Genomics + Hands-on 2 of 31 Course Objectives How to browse information about a gene How to choose a transcript Where to find sequence variations How to view multiple alignments How to use BioMart Where to go for help 3 of 31 Introduction to Ensembl Why do we have genome browsers? Why Ensembl? Ensembl genes and genomes Where to go for help? 4 of 31 Genome browsers provide a map DNase I sensitive site Histone modification Gene Conserved sequence Allele Figure adapted from the ENCODE project www.nature.com/nature/focus/encode/ 5 of 31 Genome Browsers • Ensembl Genome browser http://www.ensembl.org • NCBI Map Viewer http://www.ncbi.nlm.nih.gov/mapview/ • UCSC Genome Browser http://genome.ucsc.edu 6 of 31 Ensembl Features • The gene set. Automatic annotation based on mRNA and protein information plus manual annotation (GENCODE set). • BioMart (data export tool) • Comparative analysis (gene trees) • Variation and functional genomics • Integration with other databases (DAS) • Programmatic access via the Perl API (open source) 7 of 31 Subjects Why do we have genome browsers? Why Ensembl? Ensembl genes and genomes Where to go for help? 8 of 31 To meet a challenge… Ensembl’s AIM: To provide annotation for the biological community that is freely available and of high quality • Started in 2000 • Joint project between EBI and Sanger • Funded primarily by the Wellcome Trust, additional funding by EMBL, NIH-NIAID, EU, BBSRC and MRC 9 of 31 Genome annotation Genome annotation is the process of attaching biological information to sequences. It consists of two main steps: 1. Identifying genes on the genome. 2. Attaching biological information to genes and the genome. (For example, effects of sequence variation). 10 of 31 Ensembl Annotates Vertebrate Genomes 50 species including: Non-chordates: D. melanogaster C. elegans S. cerevisiae 11 of 31 : Extending Ensembl across the taxonomic space 48 Chordates including: 21Aspergillums 8 species species 134 species 3 Plasmodia Human 2 Arabidopsis Drosophila thaliana -falciparum 6yeast bacterial(12) clades Mouse -knowlesi Arabidopsis Caenorhabditis S.cerevisiae lyrata (5) 1 prokaryotic clades Zebrafish -vivax Oryza Anopheles S.pombe sativa gambiae Chicken Chimpanzee Pig Platypus F. D. Ciccarelli, T. Doerks, C. von Mering, C. J. Creevey, B. Snel & P. Bork. Towards automatic reconstruction of a highly resolved tree of life. Science, 3 March 2006. Slide design by 12 of 35 Jeff Almeida-King 12 of 49 31 Exploring genomes • Vertebrates focus: www.ensembl.org • Other species: www.ensemblgenomes.org 13 of 31 Subjects Why do we have genome browsers? Why Ensembl? Ensembl genes and genomes Where to go for help? 14 of 31 What is known? Genomic assemblies from sequencing consortia 15 of 31 What is known? Proteins and cDNA/mRNA sequences from the research community found in: • UniProtKB/Swiss-Prot (manually curated) • UniProtKB/TrEMBL www.uniprot.org • NCBI RefSeq (manually curated) www.ncbi.nlm.nih.gov/RefSeq Note: See pages 55 and 56 of the course booklet 16 of 31 Combining genes and genomes …tgcctgttag... Exon Untranslated+Coding Exon Coding Exon Untranslated 17 of 31 Too many pieces… Genome Aligned cDNA and protein Exon Untranslated+Coding Exon Coding Exon Untranslated 18 of 31 Ensembl shows one transcript with underlying evidence 19 of 31 Ensembl Compared with Swiss-Prot and NCBI RefSeq sequences 20 of 31 Is there any consensus? • NCBI RefSeq set ≠ UniProt set • Ensembl combines these sets • UCSC has it’s own gene set How do we come up with a consensus gene set between all these? 21 of 31 CCDS • Reaching a consensus coding sequence set for human and mouse. • 19,851 (ENS human), 17,679 (ENS mouse) (*as of Sept 2009) • If you see a “CCDS ID”, the coding sequence is agreed upon. Genome Res. 2009 Jul;19(7):1316-23. Epub 2009 Jun 4 22 of 31 VEGA/Havana • Automatic annotation pipeline: Gene building all at once (whole genome) Ensembl • Manual curation: case-by-case basis VEGA: Vertebrate Genome Annotation Havana 23 of 31 Genes and Transcripts in Ensembl High Quality: • CCDS transcripts • Ensembl/Havana merged transcripts 24 of 31 Ensembl/Havana • Transcripts are from: Ensembl Havana Ensembl/Havana merge 25 of 31 Gene Names in Ensembl • • • • ENSG### ENST### ENSP### ENSE### Ensembl Gene ID Ensembl Transcript ID Ensembl Peptide ID Ensembl Exon ID • For other species than human a suffix is added: MUS (Mus musculus) for mouse: ENSMUSG### DAR (Danio rerio) for zebrafish: ENSDARG###, etc. 26 of 31 How is all this information organised? • Ensembl Views (Website) • Ensembl Database (open source) • BioMart ‘DataMining tool’ 27 of 31 What other annotation? • • • • Non-coding (nc)RNAs IDs in other databases microarray probes, clonesets, BAC maps Other features of the genome: repeats, CpG islands • Homologs and whole genome alignments: orthologues and paralogues, protein families, syntenic regions • Variation data: Single Nucleotide Polymorphisms, InDels, CNVs • Regulatory data (a first guess at promoter and enhancer elements) • Data from external sources (DAS) 28 of 31 Subjects Why do we have genome browsers? Why Ensembl? Ensembl genes and genomes Where to go for help? 29 of 31 Help and Information • Comments and questions? [email protected] • Check out our tutorials page: www.ensembl.org/info/website/tutorials/index.html • Videos http://www.youtube.com/user/EnsemblHelpdesk • Mailing list [email protected] • Come visit our blog! http://ensembl.blogspot.com/ • FTP site: ftp://ftp.ensembl.org • Amazon Web Services: http://aws.amazon.com/publicdatasets 30 of 31 Ensembl Team Ensembl Paul Flicek (EBI), Steve Searle (Sanger Institute) Software Glenn Proctor, Andreas Kähäri, Stephen Keenan, Rhoda Kinsella, Eugene Kulesha, Ian Longden, Iliana Toneva, Jorge Zamora Comparative Genomics Functional Genomics Variation Analysis and Annotation Web Team Outreach Systems & Support Javier Herrero, Kathryn Beal, Stephen Fitzgerald, Leo Gordon Ian Dunham, Nathan Johnson, Daniel Sobral, Steven Wilder Fiona Cunningham, Pontus Larsson, Will McLaren, Graham Ritchie Jan-Hinnerck Vogel, Bronwen Aken, Susan Fairley, Thibaut Hourlier, Magali Ruffier, Simon White, Amy Tang, Amonida Zadissa Anne Parker, Ridwan Amode, Simon Brent, Maurice Hendrix, Bethan Pritchard, Steve Trevanion (VEGA) Xosé M Fernández, Jeff Almeida-King, Bert Overduin, Michael Schuster (QC), Giulietta Spudich, Jana Vandrovcova Guy Coates, James Beal, Gen-Tao Chiang, Peter Clapham, Simon Kelley, Shelley Goddard, Tracy Mumford, Kerry Smith Research Benoît Ballester, Petra Catalina Schwalie, André Faure, Markus Fritz, Damian Keefe, Alison Meynert, Dace Ruklisa, Mikhail Spivakov, David Thybert, Sander Timmer, Albert Vilella Vertebrate Genomics Chao-Kung Chen, Laura Clarke, Jonathan Hinton, Zam Iqbal, Vasudev Kumanduri, Ilkka Lappalainen, Edoardo Marcora, Pablo Marín, Damian Smedley, Richard Smth, Phil Wilkinson, Holly Zheng-Bradley Ensembl Genomes VectorBase Zebrafish Ensembl Strategy Paul Kersey, Paul Derwent, Matthias Haimel, Alan Horne, Arnaud Kerhornou, Uma Maheswari, Michael Nuhn, Dan Staines, Andy Yates Dan Lawson, Gautier Koscielny, Karyn Megy Kerstin Howe, Kim Brugger, Will Chow, Britt Reimholz, James Torrance Ewan Birney, Richard Durbin, Tim Hubbard Ensembl’s 10th Year Nucleic Acids Res. 2010 http://www.ncbi.nlm.nih.gov/pubmed/19906699 31/40