BIOINFORMATICS APPLICATIONS NOTE
Gene expression

Vol. 26 no. 9 2010, pages 1267–1268
doi:10.1093/bioinformatics/btq121

Advance Access publication March 19, 2010

CoP: a database for characterizing co-expressed gene modules
with biological information in plants
Yoshiyuki Ogata, Hideyuki Suzuki, Nozomu Sakurai and Daisuke Shibata∗
Department of Biotechnology Research, Kazusa DNA Research Institute, 2-6-7 Kazusa-Kamatari, Kisarazu,Chiba 292-0818, Japan

ABSTRACT
Summary: Using a large dataset (10 022 assays) obtained
from public plant microarray databases, we developed the CoPdatabase for associating co-expressed gene modules with biologicalinformation such as gene ontology terms and, if available, metabolic
pathway names. The Confeito algorithm developed previously in
our laboratory, which is suitable to calculate the interconnectivity
between genes in co-expressed gene network, was applied toextract co-expressed gene modules. The database includes thegene modules for Arabidopsis thaliana (thale cress) and seven crops,
Glycine max (soybean), Hordeum vulgare (barley), Oryza sativa (rice),
Populus trichocarpa (poplar), Triticum aestivum (wheat), Vitis vinifera(grape) and Zea mays (maize).
Availability: The CoP database is available at: http://webs2.kazusa.or.jp/kagiana/cop0911/
Contact: shibata@kazusa.or.jp
Received on November 12, 2009; revised on February 11, 2010;
accepted on March 16, 2010

1

INTRODUCTION

Since the decoding of the Arabidopsis genome (Arabidopsis
Genome Initiative, 2000), information on genome sequences andgene expression in plants has accumulated in public databases.
Many microarray datasets assembled from various experiments(e.g. different tissues and chemical treatments), including theAtGenExpress datasets of Arabidopsis (Schmid et al., 2005), havebeen utilized to predict co-expressed genes for assigning themto metabolic pathways (Obayashi et al., 2009; Wei et al., 2006),
transcriptional regulation (Hirai et al., 2007; Obayashi et al., 2009)
and/or biological processes (Ogata and Shibata, 2009).
There are several databases that are designed to extract coexpressed genes from plant microarray datasets and then provide
biological information with individual genes in the co-expressedgene group, facilitating investigation of gene function (see thereview of Usadel et al., 2009). Cross-species comparison of relevant
co-expressed gene groups is also useful, as seen in the database
GeneCAT (Mutwil et al., 2008) that provides comparative analysis
of Arabidopsis and barley co-expressed genes on the basis ofsequence similarity. Association of co-expressed gene modules
intentionally with biological information such as gene ontology(GO) and metabolic pathways would be useful. However, to ourknowledge, there is no such database available. Thus, we have∗

To whom correspondence should be addressed.

developed the CoP database for associating co-expressed gene
modules assembled from public large microarray datasets withbiological information and comparing these modules across plant
species to provide fundamental data for hypothesis generation ofgene function. We apply the ‘condition-independent’ co-expression
analysis to extract co-expressed modules from the whole setof microarray data, which gives only a single score, irrespectiveof tissue types and other experimental conditions, to the gene ofinterest. This approach is a suitable way to view general gene-togene relationships for the initial investigation of genes of interest(see the review of Usadel et al., 2009). In addition to the biologicalinformation such as GO terms and pathway names, the systemprovides direct links to public databases for further informationon the co-expressed gene modules. The current database utilizes
public microarray datasets from Arabidopsis thaliana (thale cress),
Glycine max (soybean; Ogata et al., 2009a), Hordeum vulgare(barley), Oryza sativa (rice), Populus trichocarpa (poplar; Ogata
et al., 2009b), Triticum aestivum (wheat), Vitis vinifera (grape) andZea mays (maize).

2DATA ACQUISITION

DNA microarray datasets were obtained from the Gene Expression
Omnibus (http://www.ncbi.nlm.nih.gov/geo/) and ArrayExpress(http://www.ebi.ac.uk/microarray-as/ae/) databases. We obtained
CEL files or MAS5-processed data files (Affymetrix GeneChip) forA.thaliana (5257 chips), G.max (2994), H.vulgare (403), O.sativa(432), P.trichocarpa (95), T.aestivum (368), V.vinifera (210) andZ.mays (263). The CEL files were processed using the Bioconductor
package 2.3.13 with R version 2.8.1 to obtain MAS5-processed text
data. The text data for each plant were standardized and then used
to calculate gene-to-gene correlation in gene expression profiles.
As a measure of the correlation, we use cosine correlation coefficientbecause it is suitable to deal with datasets that appear to be morereliable in high positive expression values than in low ones interms of the signal-to-noise ratio. See the concept text attached tothe database for details (http://webs2.kazusa.or.jp/kagiana/cop0911/concept.html).
Biological information was obtained from datasets of GObiological processes for A.thaliana (March 24, 2009) from TAIR
(http://arabidopsis.org/) and for O.sativa (March 6, 2009) fromGRAMENE (http://www.gramene.org/). To assign plant genes tometabolic pathways, we obtained information on the assignment
for Arabidopsis genes from KEGG PATHWAY (http://www.genome.jp/kegg/pathway.html) and KaPPA-View 4 (http://kpv.kazusa.or.jp/kpv4/; Tokimatsu et al., 2005).

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Associate Editor: Trey Ideker

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The dataset of Arabidopsis cDNA was obtained from theTAIR database (TAIR8_cds_20080412, April 12, 2008), thedataset of rice cDNA from RAP-DB (http://rapdb.dna.affrc.go.jp/;
prediction_nuc.fa and rep_nuc.fa, May 16, 2007) cDNA and otherplant EST datasets from the DFCI database (http://compbio.dfci.
harvard.edu/tgi/; these latest version data were obtained in February2009) for homology analysis.

3We extracted co-expressed gene modules with the Confeito
algorithm that is designed to detect highly interconnected modules
from co-expressed gene networks (Ogata et al., 2009c). The
algorithm uses a novel network index NF for each module (see http://webs2.kazusa.or.jp/kagiana/cop0911/pages/terms.html for details).
To help assess the modules statistically, we also provide thepercentile score of the NF index of the module of interest to theNF indices of all other modules.

4ASSOCIATION WITH BIOLOGICALINFORMATION

We performed homology search using NEC Homology
Searcher 4.3a software with the BLASTn algorithm (NECCorporation, Tokyo, Japan). Each gene sequence of a plant was
BLAST searched not only to all sequences of the plant to findparalogous genes within the species, but also to all sequences ofother plant to find the best hit orthologous gene. These homologous
gene sets deposited in the database are used to represent thegenes homologous to the user’s query gene. Sequence similarity
is represented with the commonly used indexes, E-value and Bit
score, and also with the harmonic mean of identity. To associateeach co-expressed gene module with biological information, thesystem compares the gene members of the module to those assigned
to a GO term of biological processes that has been defined by theGO consortium with a harmonic mean index (see the detail inthe concept text). Information of GO term association is provided
only for Arabidopsis and rice, as for these plants the GO terms areavailable with the gene codes used in the CoP database. Associationwith metabolic pathway names of the omics integration toolKaPPA-View 4 and biological pathways of the database KEGG
PATHWAY is also represented with the harmonic mean index.

5DATABASE DESIGN

5.1 The CoP portal site
The CoP portal site allows users to input query terms according
to the following steps: (i) input of query term; (ii) selection ofplant; (iii) selection of information type; and then (iv) selectionof options (see http://webs2.kazusa.or.jp/kagiana/cop0911/pages/terms.html for details). Query terms include gene identifiers (e.g.
an AGI code for A.thaliana), probe names and all or part of a genename. When multiple hits are obtained for genes or probes for a5.2

Information pages for co-expressed gene modules

The information page for each co-expressed gene module comprises
four sections. The first section provides information about theconnectivity and number of genes of the module. The Arabidopsis
page also includes a co-expressed gene network graph with thequery gene; i.e. genes are interconnected by their similarity inexpression profiles. In each network, nodes are categorized into fourfunctional types: transcription factor, binding protein, enzyme andother proteins. The second section presents a table of functionaldescriptions, including the associations of genes with biologicalprocesses, and links to additional biological information andpublic databases for each gene. By clicking on ‘More genes’, allco-expressed genes in the module are presented in the table. The
third section presents a list of microarray experiments on genes in themodule showing specific expression. The fourth section represents
a comparison between co-expressed gene modules in two plants.
Funding: The New Energy and Industrial Technology Development
Organization (NEDO) program that is part of the ‘Development ofFundamental Technologies for Controlling the Material Production
Process of Plants’ project.
Conflict of Interest: none declared.

REFERENCES
Arabidopsis Genome Initiative (2000) Analysis of the genome sequence of the flowering
plant Arabidopsis thaliana. Nature, 408, 796–815.
Hirai,M.Y. et al. (2007) Omics-based identification of Arabidopsis Myb transcription
factors regulating aliphatic glucosinolate biosynthesis. Proc. Natl Acad. Sci. USA,104, 6478–6483.
Mutwil,M. et al. (2008) GeneCAT – novel webtools that combine BLAST andco-expression analyses. Nucleic Acids Res., 36, W320–W326.
Obayashi,T. et al. (2009) ATTED-II provides coexpressed gene networks forArabidopsis. Nucleic Acids Res., 37, D987–D991.
Ogata,Y. et al. (2009a) A gene co-expression database for understanding biologicalprocesses in soybean. Plant Biotechnol., 26, 503–507.
Ogata,Y. et al. (2009b) A database for poplar gene co-expression analysis for systematic
understanding of biological processes, including stress responses. J. Wood Sci., 55,395–400.
Ogata,Y. et al. (2009c) The prediction of local modular structures in a co-expression
network based on gene expression datasets. Genome Inform., 23, 117–127.
Ogata,Y. and Shibata,D. (2009) Practical network approaches and biologic
interpretations of co-expression analyses in plants. Plant Biotechnol., 26, 3–7.
Schmid,M. et al. (2005) A gene expression map of Arabidopsis thaliana development.
Nat. Genet., 37, 501–506.
Tokimatsu,T. et al. (2005) KaPPA-View: a web-based analysis tool for integration oftranscript and metabolite data on plant metabolic pathway maps. Plant Physiol.,
138, 1289–1300.
Usadel,B. et al. (2009) Co-expression tools for plant biology: opportunities for
hypothesis generation and caveats. Plant Cell Environ., 32, 1633–1651.
Wei,H. et al. (2006) Transcriptional coordination of the metabolic network inArabidopsis. Plant Physiol., 142, 762–774.

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DETECTION OF CO-EXPRESSED GENE
MODULESquery, a list of these hits is displayed with corresponding links toindividual information pages. The complete list of the co-expressedgene modules can be displayed in descending order of the tightconnectivity by entering the search string ‘confeito’ to the ‘Gene,co-expression’.

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