GO based data analysis

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GO based data analysis
Iowa State Workshop 11 June 2009
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• All tools and materials from this workshop are
  available online at the AgBase database
  Educational Resources link.
• For continuing support and assistance please
  contact
• agbase_at_cse.msstate.edu

This workshop is supported by USDA CSREES grant
number MISV-329140.
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AgBase protein annotation process
Protein identifiers or Fasta format
GORetriever
Annotated Proteins
Proteins with no annotations
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Hypothesis generating

• Gene Ontology enrichment analysis
• GO terms that are statistically (Fishers
  exact test) over or underrepresented in a set of
  genes
• Annotation Clustering
• group similar annotations based on the
  hypothesis that they should have similar gene
  members   

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Some resources

• DAVID http//david.abcc.ncifcrf.gov/
• GOStat http//gostat.wehi.edu.au/
• EasyGO http//bioinformatics.cau.edu.cn/easygo/
• AmiGO http//amigo.geneontology.org/cgi-bin/amigo/
  term_enrichment (does not use IEA)
• Onto-Express OE2GO http//vortex.cs.wayne.edu/p
  rojects.htm
• GOEAST http//omicslab.genetics.ac.cn/GOEAST
• http//www.geneontology.org/GO.tools.shtml
• Comparison of enrichment analysis tools Nucleic
  Acids Research, 2009, Vol. 37, No. 1 113
• (Tool_Comparison_09.pdf)

DAVID and EasyGO analysis included
DAVIDEasyGo.ppt
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Database for Annotation, Visualization and
Integrated Discovery
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http//vortex.cs.wayne.edu/ontoexpress
Onto-Express analysis instructions are Available
in onto-express.ppt
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Species represented in Onto-Express
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For uploading your own annotations use OE2GO
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Comparison

• Onto-Express , EasyGO, GOstat and DAVID
• Test set 60 randomly selected chicken genes
• Used AgBase GO annotations as baseline annotations

Vandenberg et al (BMC Bioinformatics, in review)
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Networks Pathways
Iowa State Workshop 11 June 2009
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Multiple data analysis platforms
Proteomics
LIST
Transcriptomics
ESTs
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Our original aim. understand biological
phenomena.

• Bits and pieces of information
• Do not have the full picture
• How do we get back to BIOLOGY in this digital
  information landscape?

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What do we know about biological systems .

• biological systems are dynamic, not static
• how molecules interact is key to understanding
  complex systems

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Types of interactions

• protein (enzyme) metabolite (ligand)
• metabolic pathways
• protein protein
• cell signaling pathways, protein complexes
• protein gene
• genetic networks

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STRING Database
Sod1 Mus musculus
http//string.embl.de/
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Database/URL/FTP DIP http//dip.doe-mbi.uc
la.edu BIND http//bind.ca
MPact/MIPS http//mips.gsf.de/services/pp
i STRING http//string.embl.de MINT
http//mint.bio.uniroma2.it/mint IntAct
http//www.ebi.ac.uk/intact BioGRID
http//www.thebiogrid.org HPRD
http//www.hprd.org ProtCom
http//www.ces.clemson.edu/compbio/ProtCom 3did
, Interprets http//gatealoy.pcb.ub.es/3did/ P
ibase, Modbase http//alto.compbio.ucsf.edu/pibase
CBM ftp//ftp.ncbi.nlm.nih.gov/pub/cbm
SCOPPI http//www.scoppi.org/ iPfam
http//www.sanger.ac.uk/Software/Pfam/iPfam In
terDom http//interdom.lit.org.sg DIMA
http//mips.gsf.de/genre/proj/dima/index.html
Prolinks http//prolinks.doe-mbi.ucla.edu/cgibin/
functionator/pronav/ Predictome http//predictom
e.bu.edu/
PLoS Computational Biology March 2007, Volume 3
e42
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Pathways Networks

• A network is a collection of interactions
• Pathways are a subset of networks
• Network of interacting proteins that carry
  out biological functions such as metabolism and
  signal transduction
• All pathways are networks of interactions
• NOT ALL NETWORKS ARE PATHWAYS

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Biological Networks

• Networks often represented as graphs
• Nodes represent proteins or genes that code for
  proteins
• Edges represent the functional links between
  nodes (ex regulation)
• Small changes in graphs topology/architecture
  can result in the emergence of novel properties

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Yeast Protein-Protein Interaction Map
Nature 411, 2001, H. Jeong, et al
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Some resources
KEGG http//www.genome.jp/kegg/pathway.htm
l/ BioCyc http//www.biocyc.org/ Reactome
http//www.reactome.org/ GenMAPP
http//www.genmapp.org/ BioCarta
http//www.biocarta.com/ Pathguide the pathway
resource list http//www.pathguide
.org/
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Pathguide Statistics
Gallus gallus is missing
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Reactome
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What is feasible with my specific dataset?
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Systems Biology Workflow
Nanduri McCarthy CAB reviews, 2008
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Systems Biology Workflow
For a given species of interest what type of
data is available???
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Retrieval of interaction datasets

• Evaluate PPI resources such as Predictome
• Prolinks for existence of species of
  interest
• If unavailable, find orthologous proteins in
• related species that have interactions!

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I have interactions what next?

• Evaluate the quality of interactions i.e. type of
  method used for identification.what exactly are
  these methods?

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I have interactions what next?

• Evaluate the quality of interactions i.e. type of
  method used for identification.what exactly are
  these methods?

STRING Database
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PPI Identification
Computational
Experimental
Phylogenetic profile
Yeast two hybrid
Yeast two hybrid (Y2H)
Gene Cluster
TAP assays
TAP assays
Sequence coevolution
Gene Coexpression
Rosetta stone method
Protein arrays
Text mining
PLoS Computational Biology March 2007, Volume 3
e42
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PPI database comparisons
Proteins Structure, Function and Bioinformatics
63490-500 2006
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I have interactions what next?

• Evaluate the quality of interactions i.e. type of
  method used for identification.what exactly are
  these methods?
• Visualize these interactions as a network and
  analyze
• what are the available tools?