Using the Ondex system for exploring Arabidopsis regulatory networks
- 1. Using the Ondex system for exploring Arabidopsis regulatory networksArtem LysenkoUK Plant Systems Biology Workshop 2011artem.lysenko@bbsrc.ac.uk
- 2. Biological data in network representationontologiesprotein interactionsmetabolic pathways
- 3. Ondex system overviewData input& transformationData integrationVisualisationClients/ToolsHeterogeneous data sourcesONDEXIntegrationMethodsONDEX Visualization Tool KitUniProtGeneralized Object Data ModelDatabase LayerAccessionParserName basedWeb ClientAraCycParserTransitiveTavernaGOBlastParserProteinFamilyPfamData ExchangeParserPfam2GOOXL/RDFPDBLuceneParserWebServiceSource: Ondex SABR project
- 4. Sparseness of plant data
- 5. MotivationInformation about regulation in plants is limitedKEGG – two maps with 232 and 48 genes related to signallingAtRegNet – currently only covers 69 transcription factors in Arabidopsis, however data fro 9375 regulated genesOther types of data are more abundantFunctional annotationProtein-protein interactionsGene expressionUse the latter to compensate for the lack of the former
- 6. More resources = better coverageProteinsInteractions
- 7. Inference methodsAnalysis of microarray dataMeta-coexpression networks from NASC, ArrayExpress and GEO dataDatabases: ATTED-II, CoexpressDBInter species comparisonOrtholog detection methods: OrthoMCL, InparanoidDatabases: resources supporting OrthoXML formatPrediction of interactions“Interolog” and domain-domain approachesDatabases: AtPID, TAIR predicted interactomePrediction of functional roleExperimentally-determined interactionSpecies AOrthologySpecies BInferred interaction
- 8. The datasets for these application casesFunctional annotation – Gene OntologyGOA EBITAIRUniProtKBInteractionExperimental – BioGrid, IntAct, TAIRPredicted – interolog approachExpression data – gene coexpression networksTargeted subsets from NASC, ArrayExpress and GEO data
- 9. Example 1: NAR2.1-knockout microarrayNAR2.1 is required to target the high-affinity nitrate transporter NRT2.1 to plasma membraneNRT2.1 is required to take up nitrate at low internal concentrationsPossible involvement of NAR2.1 in nitrate sensingAnother nitrate transporter (NRT1.1) have now been demonstrated to also function as a sensorImage source: Miller et. al. (2007)
- 10. From clusters to regulatory relationshipsMeta-coexpression network~140 nitrogen-relevant arraysGene list – nitrogen uptake mutant, grown under low nitrogenMutant versus wild-type
- 11. From clusters to regulatory relationshipsLocalisation: chloroplastComponent of ribosomeRegulation of transcriptionMarkov clusteringFunctions at 50% coverage
- 12. From clusters to regulatory relationshipsAT1G11850.1LBD38AT2G15880.1NARS2 AT1G25550.1ATBZIP3 AT1G06040.1TGA1AT3G02790.1ARR6AT2G15880.1ATERF13 WRKY40ORA47ATERF-1 AT5G51190.1ERF104 ERF-5 Identify transcription factors in clustersATSZF2AT1G06040.1AT3G02790.1ATMYB34
- 13. Example 2: nitrogen-responsive gene listNitrogen-responsive gene list from Gutiérrezet. al. (2007)Only N-responsive genes selected
- 14. PPI-driven signalling/regulationIntegrated PPI network:
- 15. Experimental and predicted PPIs
- 16. Pull out the PPI links of regulatory significance using GO annotationGO: regulationGene list(s)
- 17. PPI-driven signalling/regulationOxidative stress responseCytokininCircadian rhythmAuxinGibberellin
- 18. Nitrogen and phytohormonesCytokinin (CK) and auxin (AUX) are key signals of nitrogen status
- 20. Different regulatory mechanisms in the shoot versus the rootImage source: Kibaet. al. (2006)
- 21. Cytokinin, nitrogen and oxidative stressNitrogen deficiency lead to lower biomass and oxidative stress
- 22. Cytokinin identified as important for these processes
- 23. Additional cytokinin in the transgenic plant reduced the effectsAcknowledgementsThe Ondex team
- 24. Senior colleagues and supervisors:
- 25. Chris Rawlings, MansoorSaqi, Michael Defoin-Platel, Tony Miller and Charlie Hodgman
- 26. Funding:
- 27. PhD studentship: BBSRC (BBS/S/E/2006/13205)
- 29. Ondex SABR project: BBSRC (BB/F006039/1)