how to access genomic information using ensembl damian smedley and xosé fernández ensembl project...

How to access genomic information

using Ensembl

Damian Smedley and Xosé Fernández

Ensembl Project

European Bioinformatics InstituteCambridge, UK

November 2004

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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)

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Our goal

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Other ordering data

to 26,720 overlapping clones

From 325,109 initial contigs

Assembly

non-redundant, “virtual contig” view

finished BAC

draft

sequenceassembly

WGS

fragment

pUCsavg size 2-4 kb

Bentley et al 2001Bruls et al 2001McPherson et al 2001Montgomery et al 2001Tilford et al 2001

mapOsoegawa et al 2001

fragment

BACsbacterial artificial chromosomesavg size 150 kb

Shizuya et al 1992Dib et al 1996Deloukas et al 1998

Mapping and Sequencing the human genome

Status of the human sequencefinished 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

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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)

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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

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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

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Freely-availableCommunity development.

– >51 Ensembl installs worldwide.

– Both public and commercial,

e.g. Gramene (CSHL)

Fugu-sg (ICMB)

Ciona-sg (Temasek)

Ensembl – Open source

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Analysis DB

CPU

Final DB

SupportingDatabases

SNP

ManualAnnotation

Ensembl

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Genome browsingwhy 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

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• Ensembl – public site + installable system

Genome browsers

• NCBI Map Viewer

• UCSC Human Genome Browser

http://www.ensembl.org

http://www.ncbi.nlm.nih.gov/mapview

http://genome.ucsc.edu

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Introduction to the

Ensembl web site Ensembl … …

takes genomic sequence assemblieshuman build 34, mouse, rat, Fugu,mosquito

adds annotation and links automated process

presents all the data on a web site

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Known genes Novel genes

• where?• genomic structure?• transcripts(s)?• protein(s)?• orthologues?• attach useful links

• how to predict?require evidence• transcripts(s)?• protein(s)?• orthologues?• attach useful links

Annotation: genes

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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

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How to get started … …

• Species homepage

• Site map

• Map View

• Text search

• BLAST

• SSAHA

• Disease View

Homepage

Site map

MapView

AnchorView

BLAST and SSAHA

BLAST and SSAHA

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Regions, maps and markers

MarkerView

SNPView

ContigView

CytoView

SyntenyView

MultiContigView

EnsemblContigView

ContigView close-up

EvidenceTranscriptsred & black(Ensembl predictions)Blue (Vega)

Customising& short cuts

Pop-up menu

ContigView - Chromosome 20 close-up

Manualannotationvia Vega

Ensembl predictions

Ensembl EST-based predictions

Forw

ard

strandR

everse strand

Other chromosomes with manual annotation from http://vega.sanger.ac.uk: 6, 7, 9, 10, 13, 14, 20, 22, X

CytoView

GeneSNPView

MarkerView

SNPView

SyntenyView

MultiContigView

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Genes & gene products

GeneView

TransViewExonView

ProteinView

FamilyView

DomainView

GOView

DiseaseView

EnsemblGeneView

TransView ExonView

ProteinView

FamilyView

GOView

DiseaseView

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Data retrieval

EnsMart

Data sets on ftp site

MySQL queries of databases

Perl API access to databases

Export View

ExportView

EnsMart

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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

MouseCytoView

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Help!

• context sensitive help pages - click

• access other documentation via generic home page

• email the helpdeskHelpDesk / Suggestions

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Thanks

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

Vega Web Team

Patrick Meidl

Steve Trevianon

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

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

Ensembl TeamEnsembl Team

November 2004