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GO-based tools for functional modeling. GO Workshop 3-6 August 2010. Functional Modeling. Grouping by function GO Slim sets GO browser tools GOSlimViewer GO enrichment analysis DAVID EasyGO/agriGO Onto-Express Funcassociate 2.0 Pathway & network analysis Hypothesis testing. - PowerPoint PPT Presentation
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GO-based tools for functional
modeling
GO Workshop3-6 August 2010
Functional Modeling Grouping by function
GO Slim sets GO browser tools GOSlimViewer
GO enrichment analysis DAVID EasyGO/agriGO Onto-Express Funcassociate 2.0
Pathway & network analysis Hypothesis testing
Grouping by function
GO Slim Sets slim sets are abbreviated versions of the GO contain broader functional terms made by different GO Consortium groups (for different
purposes, eg. plant, yeast, etc) need to cite which one you used!
More information about GO terms for each slim set can be found at EBI QuickGO:http://www.ebi.ac.uk/QuickGO/
GO Slim and Subset Guide http://www.geneontology.org/GO.slims.shtml
QuickGO: Create your own subset/slim of GO terms http://www.ebi.ac.uk/QuickGO/ GO slims tutorial available This tutorial will describe GO slims, what they are
used for and how to use QuickGO for: * creating a custom GO slim * using a pre-defined GO slim * obtaining GO annotations to a GO slim * customising a set of slimmed annotations * using statistics calculated by QuickGO to
generate graphical representations of the data
AmiGO: GO Slimmer http://amigo.geneontology.org/cgi-bin/ami
go/slimmer?session_id=4878amigo1273279396
GOSlimViewer input file
Input is a text file containing 3 tab separated columns:
1. accession
2. GO:ID
3. aspect (P,F or C)
• file provided by GORetriever and GOanna2ga
• can manually add to it from GOanna excel file
allows you to include your additional GO annotations in the analysis
GOSlimViewer output
GOSlimViewer output
GOSlimViewer output
GO Enrichment analysis
http://www.geneontology.org/
Determining which classes of gene products are over-represented or under-represented.
However…. many of these tools do not support
agricultural species the tools have different computing
requirements
A list of these tools that can be used for agricultural species is available on the workshop website at the “Summary of Tools for gene expression analysis” link.
Evaluating GO toolsSome criteria for evaluating GO Tools:1. Does it include my species of interest (or do I have to
“humanize” my list)?2. What does it require to set up (computer usage/online)3. What was the source for the GO (primary or secondary)
and when was it last updated?4. Does it report the GO evidence codes (and is IEA
included)?5. Does it report which of my gene products has no GO?6. Does it report both over/under represented GO groups
and how does it evaluate this?7. Does it allow me to add my own GO annotations?8. Does it represent my results in a way that facilitates
discovery?
Some useful expression analysis tools:
Database for Annotation, Visualization and Integrated Discovery (DAVID)
http://david.abcc.ncifcrf.gov/ AgriGO -- GO Analysis Toolkit and Database for
Agricultural Community http://bioinfo.cau.edu.cn/agriGO/ used to be EasyGO chicken, cow, pig, mouse, cereals, dicots includes Plant Ontology (PO) analysis
Onto-Express http://vortex.cs.wayne.edu/projects.htm#Onto-Express can provide your own gene association file
Funcassociate 2.0: The Gene Set Functionator http://llama.med.harvard.edu/funcassociate/ can provide your own gene association file
http://david.abcc.ncifcrf.gov/
functional grouping – including GO, pathways, gene-disease association
ID Conversion search functionally related genes regular updates online support & publications
May 2010: EasyGO replaced by agriGO
http://bioinformatics.cau.edu.cn/easygo/
enrichment analysis using either GO or Plant Ontology (PO)
40 species: chicken, cow, pig, mouse, cereals, poplar, fruits
GenBank, EMBL, UniProt Affymetrix, Operon, Agilent arrays
http://bioinfo.cau.edu.cn/agriGO/
Onto-Express
Onto-Express analysis instructions areAvailable in onto-express.ppt
http://vortex.cs.wayne.edu/projects.htm
Species represented in Onto-Express
Can upload your own annotations using
OE2GO
http://llama.med.harvard.edu/funcassociate/
Pathway & network analysis
GO, Pathway, Network Analysis Many GO analysis tools also include
pathway & network analysis Ingenuity Pathways Analysis (IPA) and
Pathway Studios – commercial software DAVID – includes multiple functional
categories Onto-Tools – includes Pathways Express
tool
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
KEGG http://www.genome.jp/kegg/pathway.html/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/
Pathways Resources
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 graph’s
topology/architecture can result in the emergence of novel properties
Types of interactions protein (enzyme) – metabolite (ligand)
metabolic pathways
protein – protein cell signaling pathways, protein complexes
protein – gene genetic networks
Sod1 Mus musculus
Network example: STRING Database
http://string.embl.de/
Database/URL/FTP
•DIP http://dip.doe-mbi.ucla.edu•BIND http://bind.ca •MPact/MIPS http://mips.gsf.de/services/ppi •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/•Pibase, 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•InterDom 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://predictome.bu.edu/
PLoS Computational Biology March 2007, Volume 3 e42
Some comments on analysis tools: > 68 GO based analysis tools listed on the
GO Consortium website (not a comprehensive list!)
several tools combine GO, pathway and network functional analysis
many different ways of visualizing the results
expanding the species supported by analysis tools – check with tool developers
check for last updates & user support information
Tutorial 5In this tutorial we will use several GO
modeling tools. We will use GOSlimViewer to summarize the GO function from the cassava data set. Next we will use two GO enrichment analysis tools, DAVID and AgriGO to do GO enrichment analysis of a maize data set and compare the results from the two tools.
http://www.agbase.msstate.edu/