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Bioinformatics Advance Access originally published online on March 23, 2007
Bioinformatics 2007 23(10):1304-1306; doi:10.1093/bioinformatics/btm106
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© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Mediante: a web-based microarray data manager

Kevin Le Brigand 1,2 and Pascal Barbry 1,2,*

1CNRS and 2University of Nice Sophia Antipolis, Institut de Pharmacologie Moléculaire et Cellulaire, UMR6097, 06560 Sophia Antipolis, France

*To whom correspondence should be addressed.


    ABSTRACT
 TOP
 ABSTRACT
 1 INTRODUCTION
 2 MEDIANTE INTERFACE
 3 IMPLEMENTATION
 4 DISCUSSION
 ACKNOWLEDGEMENTS
 REFERENCES
 

Summary: Mediante is a MIAME-compliant microarray data manager that links together annotations and experimental data. Developed as a J2EE three-tier application, Mediante integrates a management system for production of long oligonucleotide microarrays, an experimental data repository suitable for home made or commercial microarrays, and a user interface dedicated to the management of microarrays projects. Several tools allow quality control of hybridizations and submission of validated data to public repositories.

Availability: http://www.microarray.fr

Contact: barbry{at}ipmc.cnrs.fr or lebrigand{at}ipmc.cnrs.fr

Supplementary information: http://www.microarray.fr/SP/lebrigand2007/


    1 INTRODUCTION
 TOP
 ABSTRACT
 1 INTRODUCTION
 2 MEDIANTE INTERFACE
 3 IMPLEMENTATION
 4 DISCUSSION
 ACKNOWLEDGEMENTS
 REFERENCES
 
DNA microarray is a reliable technology to identify alterations of gene expression under diverse biological situations. Numerous studies, mostly monocentric, were able to classify adequately different biological samples or to highlight transcripts playing key roles in specific metabolic pathways. In order to explore billions of data points generated by multiple, rather than by one, investigators, new methods need to be developed. In that context, use of efficient tools allowing storage of raw, rather than transformed data (in order to minimize the possible loss of information caused by data transformation), and inclusion of relevant quality controls, appear mandatory. Larsson and Sandberg have recently suggested that only 40% of the data stored in public repositories might be adequate for meta-analyses (Larsson and Sandberg, 2006), supporting the need for simple though powerful microarray databases, warehousing raw data associated with DNA microarray experiments. Such databases, compliant with international standards, such as MIAME (Brazma et al., 2001), can be extremely useful as transient repositories of local projects before final submissions to public repositories, such as Gene Expression Omnibus (GEO) (Edgar et al., 2002) or ArrayExpress (Parkinson et al., 2005). Mediante was created in 2002 in the context of a collaborative program to develop long oligonucleotide microarray resources shared by the French Genopole Network (RNG), and the Microarray Programme of the Medical Research Council (MRC) (Le Brigand et al., 2006). This Anglo-French consortium has now distributed more than 6500 microarrays to the academic community, and Mediante currently serves to exchange data between the three French microarray production platforms and their end users. The Mediante visualization interface of the probes and annotations has already been described in 2006). The present note is focused on additional tools, allowing: (1) the batch selection of probes; (2) the production of long oligonucleotide microarrays and (3) the storage of hybridization and biological ancillary data.


    2 MEDIANTE INTERFACE
 TOP
 ABSTRACT
 1 INTRODUCTION
 2 MEDIANTE INTERFACE
 3 IMPLEMENTATION
 4 DISCUSSION
 ACKNOWLEDGEMENTS
 REFERENCES
 
2.1 Transcripts and probes annotations
The interface displaying information about intron–exon organization, positions of the different probes available from different suppliers (Agilent, Affymetrix, Illumina) has been already described elsewhere (2006). Annotations can be browsed by accession numbers, gene symbol, alias symbol, Unigene ID, sequence descriptors, Gene Ontology term or chromosomal localization. Subforms provide additional information about Gene Ontology annotations, tissue distribution and bibliographic references.

The batch query tool allows to: (1) upload a list of transcripts in a Fasta format, or select them from the Mediante collection of transcripts; (2) identify probes belonging to the Mediante collection of oligonucleotides that match the query transcripts; (3) visualize in an interactive JSP page the alignments between query sequences and matching probes. Probes can then be selected (Fig. 1A) according to additional available annotations (Fig. 1B). At the end of this process, the corresponding ‘virtual microarray’ can be saved, downloaded or validated by other Mediante collaborators.


Figure 1
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Fig. 1. (A) Summary of a batch query. Three sequences of interest (identifiers indicated on left) were blasted against the Mediante database of human oligonucleotides. Colored boxes indicate matching Mediante oligonucleotides. The user can select from this interactive JSP page one probe per query sequence by clicking on the top box of the oligonucleotide of interest. ‘Optimal’ probes, as defined in Le Brigand et al. (2006), are colored in blue. Probes selected by the user are colored in yellow. (B) Summary information about Refseq transcript NM_001652. Clickable links to databases are provided. Probes available from different suppliers that match the transcript are indicated. (C) MA-plot. Quality plots can be visualized for each microarray. (D) Spot visualization. Morphology of the spots of interest (statistically significant probes, controls, ...) can be easily checked.

 
2.2 Microarray production
Mediante currently centralizes information about microarray production and quality control from several DNA microarray production platforms through specific interfaces. Workflow has been optimized to store information associated with printing of collections of oligonucleotides organized in multiwell plates. When all information about production has been provided, the interface generates a *.gal file, which links spots to the latest Mediante annotations. Software such as GenepixTM or Bioconductor uses *.gal files to link together hybridization and sequence information.

2.3 Experimental designs and hybridizations
At the end of a hybridization, data files associated with the microarray experiment can be uploaded in one step using a specific JSP form. Acceptable formats correspond currently to.gpr files for the quantification (generated by GenepixTM) and.tiff files for the images. Such a process creates a link between (1) the uploaded data, (2) a specific DNA microarray previously documented into the database by one of the plat-forms of production (this microarray can possibly correspond to a commercial microarray) and (3) the description of the biological samples documented in a MIAME compliant format through specific JSP forms. Hybridization can then be assessed by analyzing quality plots (Fig. 1C) or by visualizing spots corresponding to specific probes (Fig. 1D). Data can be easily exported from Mediante to other applications: (i) statistical analysis software such as the Bioconductor environment of R (Gentleman et al., 2004), (ii) public repositories such as GEO or ArrayExpress. A project can be viewed by other authorized Mediante users in the context of a collaborative work (defined by the Mediante administrator), or shared with the entire Mediante community (by attributing reading rights to the default user). Help pages are provided to guide the users into the workflow of Mediante. Additional information, such as normalized data files or files containing the outputs of a statistical analysis can also be stored in Mediante according to the MIAME specifications.


    3 IMPLEMENTATION
 TOP
 ABSTRACT
 1 INTRODUCTION
 2 MEDIANTE INTERFACE
 3 IMPLEMENTATION
 4 DISCUSSION
 ACKNOWLEDGEMENTS
 REFERENCES
 
The MEDIANTE microarray data manager is a J2EE platform deployed under a Tomcat web server. It is based on a PostgreSQL relational database organized into four distinct related modules: (i) annotation of the transcripts, (ii) annotation of the probes, (iii) microarray production and (iv) information about biological experiments and hybridizations. The schema of the database is provided as Supplementary Material. Source code is available on request. Transcripts and oligonucleotides annotations are updated using a set of Perl scripts run after each release of Refseq or ENSEMBL databases. Mediante is currently run on a bi-processor Intel Pentium Xeon 3.2GHz, with 8GB of RAM and 2TB of hard disk in a RAID5 configuration. Access to Mediante is free, but conditioned to a free registration.


    4 DISCUSSION
 TOP
 ABSTRACT
 1 INTRODUCTION
 2 MEDIANTE INTERFACE
 3 IMPLEMENTATION
 4 DISCUSSION
 ACKNOWLEDGEMENTS
 REFERENCES
 
Mediante is currently used for more than three years to exchange information between three French sites of production (IPMC, Sophia Antipolis; CEA/SGF, Evry; IGBMC, Illkirch) and more than 450 users. The web-based application has been used to document 143 microarray productions, corresponding to eight distinct microarray designs and more than 7500 microarrays (including 6500 RNG/MRC arrays) which have been distributed within 368 distinct projects. A total of 1200 hybridizations are currently ready for submission to GEO or to ArrayExpress.

With its LIMS capabilities, and tools for annotation retrieval or for cross-platform comparisons, Mediante provides a comprehensive solution to work with long oligonucleotide microarray. Accent was rather given on ad hoc storage tools than on biostatistical analysis tools, since several excellent tools are already available elsewhere (Gentleman et al., 2004; Saeed et al., 2003; Vaquerizas et al., 2005). Further development of exchange formats with these tools will undoubtedly simplify data mining of microarray experiments.

Mediante corresponds to an operational tool, already accessible to a broad community of microarray users, which has demonstrated its excellent stability and efficiency. This is especially due to the Java J2EE environment, which is an industry standard for developing portable, robust, scalable and secure server-side applications. Mediante integrates several useful tools such as (1) a visualization tool, comparing probes available from distinct platforms, (2) a ‘virtual microarray’ designer, allowing the selection or the optimization of probes collections, (3) some quality control viewers, checking the quality of the data and (4) a tool allowing a straightforward submission of data to GEO and ArrayExpress.


    ACKNOWLEDGEMENTS
 TOP
 ABSTRACT
 1 INTRODUCTION
 2 MEDIANTE INTERFACE
 3 IMPLEMENTATION
 4 DISCUSSION
 ACKNOWLEDGEMENTS
 REFERENCES
 
This project was supported by grants from RNG, INCa (PL0079), CNRS, INRIA, GIP-HMR and VLM. We are grateful to Géraldine Rios, Virginie Magnone and Virginie Virolle for precious technical assistance and to Franck Aguila for artwork. Funding to pay the Open Access publication charges was provided by CNRS.

Conflict of Interest: none declared.


    FOOTNOTES
 
Associate Editor: Joaquin Dopazo

Received on February 16, 2007; accepted on March 12, 2007

    REFERENCES
 TOP
 ABSTRACT
 1 INTRODUCTION
 2 MEDIANTE INTERFACE
 3 IMPLEMENTATION
 4 DISCUSSION
 ACKNOWLEDGEMENTS
 REFERENCES
 

    Brazma A, et al. Minimum information about a microarray experiment (MIAME)-toward standards for microarray data. Nat. Genet. (2001) 29:365–371.[CrossRef][Web of Science][Medline]

    Edgar R, et al. Gene expression omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res. (2002) 30:207–210.[Abstract/Free Full Text]

    Gentleman RC, et al. Bioconductor: open software development for computational biology and bioinformatics. Genome Biol. (2004) 5:R80.[CrossRef][Medline]

    Larsson O, Sandberg R. Lack of correct data format and comparability limits future integrative microarray research. Nat. Biotechnol. (2006) 24:1322–1323.[CrossRef][Web of Science][Medline]

    Le Brigand K, et al. An open-access long oligonucleotide microarray resource for analysis of the human and mouse transcriptomes. Nucleic Acids Res. (2006) 34:e87.[Abstract/Free Full Text]

    Parkinson H, et al. ArrayExpress – a public repository for microarray gene expression data at the EBI. Nucleic Acids Res. (2005) 33:D553–D555.[Abstract/Free Full Text]

    Saeed A, et al. TM4: a free, open-source system for microarray data management and analysis. Biotechniques (2003) 34:374–378.[Web of Science][Medline]

    Vaquerizas J, et al. GEPAS, an experiment-oriented pipeline for the analysis of microarray gene expression data. Nucleic Acids Res. (2005) 33:W616–W620.[Abstract/Free Full Text]


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This Article
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