How to access genomic information using Ensembl

How to access genomic information using Ensembl Damian Smedley and Xosé Fernández Ensembl Project European Bioinformatics Institute Cambridge, UK November 2004 Schedule Today Introduction to the Ensembl system Hands-on examples to introduce the system Evaluating genes and transcripts Variation in Ensembl (SNPs, haplotypes) Tomorrow Data mining with EnsMart Comparative genomics and proteomics in Ensembl BioMart Advanced topics (Upload your own data, DAS) 2 of 45 Our goal 3 of 45 Assembly From 325,109 initial contigs Other ordering data non-redundant, “virtual contig” view to 26,720 overlapping clones 4 of 45 Mapping and Sequencing the human genome BACs fragment Shizuya et al 1992 Dib et al 1996 Deloukas et al 1998 Osoegawa et al 2001 bacterial artificial chromosomes avg size 150 kb map WGS sequence assembly draft finished BAC pUCs avg size 2-4 kb fragment Bentley et al 2001 Bruls et al 2001 McPherson et al 2001 Montgomery et al 2001 Tilford et al 2001 Status of the human sequence finished red /orange ~96% (99.999% accurate) 30-40% repetitive elements (eg Alpha satellite, Alu repeats) All known genes, correctly identified (99.74%) heterochromatin ~4% grey Assembled draft sequence totals 2.85 Gb Human genome: Current status • 22,287 'gene loci‘ defined, consisting of 19,599 protein-coding genes in the human genome and 2,188 DNA additional segments ‘predicted’ to be protein-coding genes – 1183 genes ‘were born’ in the last 60-100 My – ~ 30 genes ‘died’ in a similar time period Finishing the euchromatic sequence of the human genome, Nature 431:931-45 (2004) 7 of 45 Ensembl - project aims • funded to provide metazoan genomes to the world • aims to provide the world’s best automated genome annotation • a leading group for human and mouse analysis • all software, data and results freely available 8 of 45 Ensembl - project background • • • • group split between EBI and Sanger mainly Wellcome Trust funded largest dedicated compute in biology in Europe developer community > 100 people, including companies 9 of 45 Ensembl – Open source Freely-available Community development. – >51 Ensembl installs worldwide. – Both public and commercial, e.g. Gramene (CSHL) Fugu-sg (ICMB) Ciona-sg (Temasek) 10 of 45 Ensembl Final DB Supporting Databases SNP Manual Annotation Analysis DB CPU 11 of 45 Genome browsing why present the whole genome? • • • • • Explore what is in a chromosome region See features in and around a specific gene Search & retrieve across the whole genome Investigate genome organization Compare to other genomes 12 of 45 Genome browsers • Ensembl – public site + installable system • UCSC Human Genome Browser • NCBI Map Viewer http://www.ensembl.org http://www.ncbi.nlm.nih.gov/mapview http://genome.ucsc.edu 13 of 45 Introduction to the Ensembl web site Ensembl … … takes genomic sequence assemblies human build 34, mouse, rat, Fugu,mosquito adds annotation and links automated process presents all the data on a web site 14 of 45 Annotation: genes Known genes • where? • genomic structure? • transcripts(s)? • protein(s)? • orthologues? • attach useful links Novel genes • how to predict? require evidence • transcripts(s)? • protein(s)? • orthologues? • attach useful links 15 of 45 Annotation: other features • • • • markers and SNPs cytogenetic bands repeated sequences ESTs & other sequence records where do they show sequence similarity? • regions homologous to other species 16 of 45 How to get started … … • • • • • • • Species homepage Site map Map View Text search BLAST SSAHA Disease View 17 of 45 Homepage Site map MapView AnchorView BLAST and SSAHA BLAST and SSAHA Regions, maps and markers ContigView CytoView SyntenyView MultiContigView MarkerView SNPView 23 of 45 Ensembl ContigView ContigView close-up Customising & short cuts Evidence Transcripts red & black (Ensembl predictions) Blue (Vega) Pop-up menu ContigView - Chromosome 20 close-up Manual annotation via Vega Ensembl predictions Other chromosomes with manual annotation from http://vega.sanger.ac.uk: 6, 7, 9, 10, 13, 14, 20, 22, X Forward strand Reverse strand Ensembl EST-based predictions CytoView GeneSNP View MarkerView SNPView Synteny View MultiContig View Genes & gene products GeneView TransView ExonView ProteinView GOView DiseaseView 32 of 45 FamilyView DomainView Ensembl GeneView TransView ExonView Protein View Family View GOView DiseaseView Data retrieval EnsMart Export View Data sets on ftp site MySQL queries of databases Perl API access to databases 39 of 45 ExportView EnsMart Mouse differences • Genomic sequence assembly based on whole genome shotgun, with finished ‘stitched’ BACs • BACs are shown in CytoView (FPC map), but for most no sequence is available 42 of 45 Mouse CytoView Help! • context sensitive help pages click • access other documentation via generic home page • email the helpdesk HelpDesk / Suggestions 44 of 45 Thanks Ensembl Team 45 of 45 Ensembl Team Database Schema and Core API Arne Stabenau Yuan Chen Ian Longden Craig Melsopp Glenn Proctor Daniel Ríos Guy Slater Distributed Annotation System Andreas Kähäri Project Leader Ewan Birney (EBI) Tim Hubbard (Sanger) Ensembl Web Team James Stalker Fiona Cunningham James Smith Analysis and Annotation Pipeline Val Curwen Steve Searle Dan Andrews Mario Caccamo Laura Clarke Martin Hammond Jan Hinnerck-Vogel Kevin Howe Vivek Iyer Kerstin Jekosch Felix Kokocinski Simon White Vega Web Team Patrick Meidl Steve Trevianon User Support Xosé Mª Fernández Michael Schuster Comparative Genomics Abel Ureta-Vidal Javier Herrero Sánchez Jessica Severin Cara Woodwark EnsMart & BioMart Arek Kasprzyk Damian Keefe Darin London Damian Smedley November 2004