Investigating Genomes with Ensembl

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Investigating Genomes with Ensembl

• Drs. Bert Overduin and Giulietta Spudich

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Overview of the day

• Introduction and website walk-through
• Hands-on exercises (the browser)
• Tea/Coffee
• Introduction to BioMart
• Hands-on exercises (BioMart)
• Lunch
• Determining the gene set
• Hands-on exercises (gene set)
• Tea/Coffee
• Variations presentation and hands-on

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Introducing

• Genome browsing a comparison
• Consensus genes
• Ensembl annotation and software
• How to find help

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Sequencing the genome
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What can we learn about genomes?

• Within one genome regulatory elements, gene
  order, chromatin structure
• Through comparative studies Evolution, conserved
  regions, rearrangements
• Gene quality and prediction.

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Genome Browsers Today

• Ensembl Genome browser
• http//www.ensembl.org
• NCBI Map Viewer
• http//www.ncbi.nlm.nih.gov/mapview/
• UCSC Genome Browser
• http//genome.ucsc.edu

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Ensembl Genome Browser
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NCBI Map Viewer
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UCSC Genome Browser
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What Distinguishes Ensembl from the UCSC and NCBI
Browsers?

• The gene set. Automatic annotation based on mRNA
  and protein information.
• Programmatic access via the Perl API (open
  source)
• BioMart
• Integration with other databases (DAS)
• Comparative analysis (gene trees)

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Challenges of genome browsers

• Increasing sequence information

198,879,188,987 nt (Aug 2007)
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Challenges of genome browsers

• Increasing annotation ENCODE
• Pilot project completed in 2007 1 of human
  genome
• Discovered promoter elements are on either side
  of the transcription start site

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To meet a challenge

• Ensembls AIM To provide annotation for the
  biological community that is freely available and
  of high quality
• Started in 1999
• Joint project between EBI and Sanger
• Funded primarily by the Wellcome Trust,
  additional funding by EMBL, NIH-NIAID, EU, BBSRC
  and MRC
• Team of ca. 40 people, led by Ewan Birney (EBI)
  and Tim Hubbard (Sanger)

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The Ensembl gene set

• All Ensembl genes start from a known protein or
  mRNA
• Sequence Ensembl
• Assembly gene set

mRNAs protein

• An initial alignment of protein and mRNA to the
  genome
• begins the Genebuild.

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Have you heard of

• Ensembl strives for best possible gene set
• www.ensembl.org
• Havana (VEGA) same goal
• http//vega.sanger.ac.uk
• HGNC a unique name and symbol for every gene in
  human
• http//www.genenames.org/
• UniProt focus on proteins, and functional
  information
• www.uniprot.org

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Ensembl vs Havana annotation

• All genes at once
• (Ensembl Genebuild)
• Quick, keeps current
• Consistent annotation
• Can apply rules to more
• species

• Gene by gene
• (Havana/ VEGA)
• Flexible, can deal with inconsistencies
• Consult publications as well as databases
• Out of the Ordinary Biology
• However Slow, Expensive

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Merging sets

• Havana transcripts are incorporated into Ensembl
• UniProt proteins are aligned to the genome in the
  Ensembl genebuild
• UniProt imports Ensembl peptides for human
• HGNC moved to Hinxton coordination

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Consensus across genome browsers the CCDS
sethttp//www.ensembl.org/info/about/docs/ccds.ht
ml

• A protein is deposited into the Consensus CDS
  protein set or CCDS set if
• NCBI
• UCSC
• Havana
• Ensembl
• have determined the same sequence.

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More about Ensembl

• Genome browsing a comparison
• Consensus genes
• Ensembl annotation and software
• How to find help

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Ensembl Genes biological basis
All Ensembl gene predictions are based on
proteins and mRNAs in

• UniProt/Swiss-Prot (manually curated)
• UniProt/TrEMBL
• NCBI RefSeq (manually curated)

Protein/ mRNA
Sequence Assembly
Ensembl Genes
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Genes and Transcripts in Ensembl

• Ensembl known genes or transcripts
• Ensembl novel genes or transcripts
• Ensembl EST genes or transcripts
• Non-Ensembl genes
• Imports for yeast, c. elegans, fly, mosquito,
  takifugu and tetraodon

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Names in Ensembl

• ENSG Ensembl Gene ID
• ENST Ensembl Transcript ID
• ENSP Ensembl Peptide ID
• ENSE 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.

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Gene Structure in Ensembl
Calmodulin Chicken
No UTRs
Calmodulin Human
UTRs annotated
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What annotation is available?

• Gene/transcript/peptide models (coding and
  noncoding (ncRNAs))
• IDs in other database
• Mapped cDNAs, peptides, micro array probes, BAC
  clones etc.
• Cytogenetic bands, markers, repeats etc.
• Comparative data
• orthologues and paralogues, protein families,
  whole genome alignments, syntenic regions
• Variation data
• Single Nucleotide Polymorphisms (SNPs)
• Regulatory data
• best guess set of regulatory elements from
  ENCODE
• Data from external sources (DAS)

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Specific data sources

• Microarrays (Affimetrix, Illumina, Agilent)
• GO (Gene Ontology functional classes)
• http//www.geneontology.org/
• OMIM (human diseases and phenotypes)
• http//www.ncbi.nlm.nih.gov/sites/entrez?db
  OMIM
• Identifiers in Entrez, UniProt, Refseq, etc
• PDB, MSD (structural databases)
• http//www.rcsb.org/pdb/
• http//www.ebi.ac.uk/msd/

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Interpro
Collection of protein data Sequences, Motifs,
Structures
http//www.ebi.ac.uk/interpro/
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How is this information organised?

• Ensembl Views (Website)
• Ensembl Database (open source)
• (Perl API, FTP site)
• BioMart DataMining tool

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Ensembl Open Source

• Data and software freely available
• More than 50 installs worldwide
• Academia and industry
• Local or available via the web
• Mirrors with Ensembl data, e.g.
  http//ensembl.genome.tugraz.at/index.html
• http//ensembl.genomics.org.cn/
• or user projects with own data

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Powered by Ensembl
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Help and Information

• Use our helpdesk!
• helpdesk_at_ensembl.org
• View our help pages!
• (the using Ensembl link)
• View our animated tutorials
• http//www.ensembl.org/common/Workshops_Online
  
• Mailing lists
• ensembl-announce_at_ebi.ac.uk
• Come visit our blog!
• http//ensembl.blogspot.com/

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Ensembl Team