Using the Ondex system for exploring Arabidopsis regulatory networks

Using the Ondex system for exploring Arabidopsis regulatory networks
Artem Lysenko
AAB conference, 14-15 April 2011
artem.lysenko@bbsrc.ac.uk

Biological data in network representation
ontologies
protein interactions
metabolic pathways

Ondex system overview
Data input& transformation
Data integration
Visualisation
Clients/Tools
Heterogeneous
data sources
ONDEX
Integration
Methods
ONDEX
Visualization
Tool Kit
UniProt
Generalized Object Data Model
Database Layer
Accession
Parser
Name based
Web Client
AraCyc
Parser
Transitive
Taverna
GO
Blast
Parser
ProteinFamily
Pfam
Data Exchange
Parser
Pfam2GO
OXL/RDF
PDB
Lucene
Parser
WebService
Source: Ondex SABR project

Sparseness of plant data

Motivation
Information about regulation in plants is limited
KEGG – two maps with 232 and 48 genes related to signalling
AtRegNet – currently only covers 69 transcription factors in Arabidopsis, however data fro 9375 regulated genes
Other types of data are more abundant
Functional annotation
Protein-protein interactions
Gene expression
Use the latter to compensate for the lack of the former

More resources = better coverage
Proteins
Interactions

Inference methods
Analysis of microarray data
Meta-coexpression networks from NASC, ArrayExpress and GEO data
Databases: ATTED-II, CoexpressDB
Inter species comparison
Ortholog detection methods: OrthoMCL, Inparanoid
Databases: resources supporting OrthoXML format
Prediction of interactions
“Interolog” and domain-domain approaches
Databases: AtPID, TAIR predicted interactome
Prediction of functional role
Experimentally-determined interaction
Species A
Orthology
Species B
Inferred interaction

The datasets for these application cases
Functional annotation – Gene Ontology
GOA EBI
TAIR
UniProtKB
Interaction
Experimental – BioGrid, IntAct, TAIR
Predicted – interolog approach
Expression data – gene coexpression networks
Targeted subsets from NASC, ArrayExpress and GEO data

Example 1: NAR2.1-knockout microarray
NAR2.1 is required to target the high-affinity nitrate transporter NRT2.1 to plasma membrane
NRT2.1 is required to take up nitrate at low internal concentrations
Possible involvement of NAR2.1 in nitrate sensing
Another nitrate transporter (NRT1.1) have now been demonstrated to also function as a sensor
Image source: Miller et. al. (2007)

From clusters to regulatory relationships
Meta-coexpression network
~140 nitrogen-relevant arrays
Gene list – nitrogen uptake mutant, grown under low nitrogen
Mutant versus wild-type

Localisation: chloroplast
Component of ribosome
Regulation of transcription
Markov clustering
Functions at 50% coverage

AT1G11850.1
LBD38
AT2G15880.1
NARS2
AT1G25550.1
ATBZIP3
AT1G06040.1
TGA1
AT3G02790.1
ARR6
AT2G15880.1
ATERF13
WRKY40
ORA47
ATERF-1
AT5G51190.1
ERF104
ERF-5
Identify transcription factors in clusters
ATSZF2
AT1G06040.1
AT3G02790.1
ATMYB34

Example 2: nitrogen-responsive gene list
Nitrogen-responsive gene list from Gutiérrezet. al. (2007)
Only N-responsive genes selected

PPI-driven signalling/regulation
Integrated PPI network:
Experimental and predicted PPIs
Pull out the PPI links of regulatory significance using GO annotation
GO: regulation
Gene list(s)

PPI-driven signalling/regulation
Oxidative stress response
Cytokinin
Circadian rhythm
Auxin
Gibberellin

Nitrogen and phytohormones
Cytokinin (CK) and auxin (AUX) are key signals of nitrogen status
Regulation of uptake
Different regulatory mechanisms in the shoot versus the root
Image source: Kibaet. al. (2006)

Cytokinin, nitrogen and oxidative stress
Nitrogen deficiency lead to lower biomass and oxidative stress
Cytokinin identified as important for these processes
Additional cytokinin in the transgenic plant reduced the effects

Acknowledgements
The Ondex team
Senior colleagues and supervisors:
Chris Rawlings, MansoorSaqi, Michael Defoin-Platel, Tony Miller and Charlie Hodgman
Funding:
PhD studentship: BBSRC (BBS/S/E/2006/13205)
Ondex development:
Ondex SABR project: BBSRC (BB/F006039/1)

Using the Ondex system for exploring Arabidopsis regulatory networks

by Catherine Canevet on Apr 20, 2011

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Using the Ondex system for exploring Arabidopsis regulatory networks — Presentation Transcript