ACEEE Int. J. on Information Technology, Vol. 01, No. 03, Dec 2011       3D Visual Integration of Spatio-Temporal Gene    ...
ACEEE Int. J. on Information Technology, Vol. 01, No. 03, Dec 2011information on spatio-temporal gene expression, it is ye...
ACEEE Int. J. on Information Technology, Vol. 01, No. 03, Dec 2011that need to be annotated correctly with terms from our ...
ACEEE Int. J. on Information Technology, Vol. 01, No. 03, Dec 2011are accessed to retrieve the required data. The reconstr...
ACEEE Int. J. on Information Technology, Vol. 01, No. 03, Dec 2011                                                        ...
ACEEE Int. J. on Information Technology, Vol. 01, No. 03, Dec 2011and the areas where a gene is expressed for spatial gene...
ACEEE Int. J. on Information Technology, Vol. 01, No. 03, Dec 2011                        ACKNOWLEDGMENTS                 ...
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3D Visual Integration of Spatio-Temporal Gene Expression Patterns on Digital Atlas of Zebrafish Embryo using Web Service

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Gene expression patterns analysis with microarray
provides quantitative information that shows how a gene is
expressed under a particular condition. Whole mount in situ
hybridization, on the other hand, can be used to capture the
spatio-temporal characteristics of the gene expression pattern.
Therefore, visual integration of gene expression data from
both techniques with a digital atlas data of a model-organism
can help identifying not only spatial and temporal but also
quantitative aspects of gene expression in different stages of
development. In this paper, we present an approach using web
services to provide an integrative online visualization of gene
expression patterns in within a digital atlas of zebrafish in
different stages of development. We developed SOAP web
services that provide programmatic access to the 3D data and
spatial-temporal whole mount gene expression data to our
readily developed information systems; the 3D digital atlas of
zebrafish development and the Gene Expression Management
System (GEMS). We also created web applications that exploit
the newly developed web services to retrieve data from our
repositories. The web applications also uses the web services
to retrieve relevant quantitative microarray analysis gene
expression data from community resources; i.e. the
ArrayExpress Atlas. All the gene expression patterns data and
the 3D atlas data are subsequently integrated using ontology
based mapping. In order to deliver the integrated visualization
to end users, we developed a Java based 3D-viewer client that
can be integrated in a web interface allowing users to visualize
the information over Internet.

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3D Visual Integration of Spatio-Temporal Gene Expression Patterns on Digital Atlas of Zebrafish Embryo using Web Service

  1. 1. ACEEE Int. J. on Information Technology, Vol. 01, No. 03, Dec 2011 3D Visual Integration of Spatio-Temporal Gene Expression Patterns on Digital Atlas of Zebrafish Embryo using Web Service D. Potikanond, F. J. Verbeek Section Imaging and Bioinformatics, Leiden Institute of Advanced Computer Science Leiden University, Leiden, The Netherlands Email: {dpotikan, fverbeek}@liacs.nlAbstract—Gene expression patterns analysis with microarray interact to control biological processes. Identifying bothprovides quantitative information that shows how a gene is temporal and spatial aspects of gene expression inexpressed under a particular condition. Whole mount in situ developmental is a crucial step for additional functionalhybridization, on the other hand, can be used to capture the analysis of genes. The microarray technique [4] is one of thespatio-temporal characteristics of the gene expression pattern.Therefore, visual integration of gene expression data from major experimental breakthroughs enabling high throughputboth techniques with a digital atlas data of a model-organism measurement and analysis of the expression patterns of (tenscan help identifying not only spatial and temporal but also of) thousands of genes simultaneously [5]. However, in multi-quantitative aspects of gene expression in different stages of cellular organism such as zebrafish, gene expressiondevelopment. In this paper, we present an approach using web influences the development of a cell or group of cells.services to provide an integrative online visualization of gene Therefore whole-specimen microarray analysis cannot fullyexpression patterns in within a digital atlas of zebrafish in document the spatio-temporal relations. Whole mount in situdifferent stages of development. We developed SOAP web hybridization, on the other hand, can be used to obtain suchservices that provide programmatic access to the 3D data and information. To this end, we built the Gene Expressionspatial-temporal whole mount gene expression data to ourreadily developed information systems; the 3D digital atlas of Management System (GEMS) [6] as an information systemzebrafish development and the Gene Expression Management for 3D spatio-temporal gene expression patterns which areSystem (GEMS). We also created web applications that exploit generated through Fluorescent In Situ Hybridizationthe newly developed web services to retrieve data from our (zebraFISH) [7] protocol.repositories. The web applications also uses the web services There are a number of information systems providingto retrieve relevant quantitative microarray analysis gene information on zebrafish anatomy and/or gene expressionexpression data from community resources; i.e. the data such as the Zebrafish Information Network (ZFIN) [8],ArrayExpress Atlas. All the gene expression patterns data and ArrayExpress [9], Entrez Gene [10] and Ensembl [11]. However,the 3D atlas data are subsequently integrated using ontology the anatomical data and gene expression data are typicallybased mapping. In order to deliver the integrated visualizationto end users, we developed a Java based 3D-viewer client that not integrated nor represented in such a way that they cancan be integrated in a web interface allowing users to visualize be visualized jointly in a 3D context. To help understandingthe information over Internet. the spatio-temporal context of genes expression and the involvement in changing anatomical structures, it is importantIndex Terms—Visualization, Web services, Zebrafish Atlas, 3D to have a visualization system that integrates data from thesereconstruction, Gene expression patterns different domains. For example, in the mouse (Mus musculus), there are the e-Mouse Atlas Project (EMAP) [12], the e-Mouse I. INTRODUCTION Atlas of Gene Expression (EMAGE) [13] and the Digital 3D imaging and graphical models have been used Atlasing and Standardization in the Mouse Brain [14]. Theeffectively as a common technical framework for representing Berkeley Drosophila Transcription Network Project (BDTNP)spatial information in biomedical research. Among the well- provides resources and visualization tools for viewing 3Dknown techniques for capturing 3D data are the serial gene expression patterns in early Drosophila embryo at cellularsectioning methods [1, 2]. These methods are used to produce resolution [15, 16]. However, there is no such thing available3D contour information from multiple regions of interest for zebrafish.(ROIs) in 3D data and thereby allowing reconstructing 3D In this paper, we describe an approach to provide websurface models. Earlier, we created the 3D digital atlas of services that helps visualizing gene expression informationzebrafish development [3] which provides an online 3D within 3D graphical models of zebrafish atlas. This way,visualization of the anatomy in the zebrafish embryo. It serves detailed information about gene expression in zebrafishas a framework of reference for researchers. Therefore in the becomes available embedded into their 3D spatial context.context of the atlas, ROIs are anatomical domains in zebrafish To provide programming interfaces to access our 3Dembryo. One of the crucial challenges in developmental reconstruction data and gene expression patterns data, webiology and molecular genetics is to determine how genes have created the 3D reconstruction (TDR) and the GEMS web services. Even though GEMS provides semantic© 2011 ACEEE 69DOI: 0.IJIT.01.03. 28
  2. 2. ACEEE Int. J. on Information Technology, Vol. 01, No. 03, Dec 2011information on spatio-temporal gene expression, it is yet to histological section images of a zebrafish embryo using ourprovide quantitative gene expression data. Hence we need dedicated acquisition station [2]. to retrieve this related information from a microarray gene The image datasets for spatial gene expression patterns,expression resource, the ArrayExpress Atlas [17, 18]. The on the other hand, are produced using the zebraFISH protocol.ArrayExpress Atlas of Gene Expression contains a subset of The patterns are acquired with the confocal laser scannercurated and re-annotated archive data from the ArrayExpress microscope as multi-channel 3D images containing the outlineRepository which is one of the recommended international of the embryo and the spatial patterns of gene expression inrepositories to archive publication related functional separated channels. The next step is to create 3Dgenomics data [19]. It can be queried for individual gene reconstruction models from both atlas and gene expressionexpression under different biological conditions across image datasets using our reconstruction software, TDR-experiments. 3Dbased [2] (Fig. 1). The reconstruction software is basically In order to integrate these data correctly we need to a tool for 3D annotation and surface reconstruction. We usedprovide a basis for cross-domain communication. In this work, a graphical annotation to specify domains of interest which,we used controlled vocabularies from standard ontologies in this context, are the boundaries of anatomical domainsto annotate the anatomical domains and genes domains on and/or patterns of gene expression. Textual annotation isboth atlas and gene expression patterns data. This allows accomplished by attaching a term to each graphicalour data to be linked together and also enables interoperability annotation. Anatomical domains are annotated withand communication with external community resources as anatomical terms from the Developmental Anatomy Ontologywell. (DAOZ) [21] and gene expression patterns data are annotated To this end, we have developed the Bio-Visualization web with proper gene terms from GEMS. In fact, all controlledservice as an intermediate component that is responsible for vocabularies in both DAOZ and GEMS are extracted fromretrieving related information from the underlying web the standard ontologies, i.e.,services, including the ArrayExpress Atlas web service. TheBio-Visualization filters and integrates all related geneexpression data from external information source(s) onto theexisting reconstruction model in order to generate a newvisualization model. The web service is designed to beextensible to support more external information source in thefuture. In support of this work, we developed web applicationsbased on the web services that provide the underlying datarequired. The web applications provide an overview and allowusers to query on our 3D digital atlas along with related geneexpression data. In order to deliver the data to end users, weintegrate our Java based 3D-viewer (TDRViewer) with theweb applications allowing users to visualize the integratedvisualization over Internet. II. CONSTRUCTING INFORMATON MODEL In this section the acquisition of the raw data for creatingboth reconstruction models and patterns of gene expressionwill be discussed. The 3D reconstruction models and 3D geneexpression patterns data in GEMS are created from 3D-imagedataset, however, from different modalities. The input data inboth cases need to be annotated using terms from standardontologies. The only difference is that the annotation forreconstruction models is done before submitting the modelsto the TDR repository whereas annotation for the geneexpression data in GEMS has to be done as part of thesubmission process.A. The 3D Reconstruction Models Figure 1. The TDR-3Dbase reconstruction software. This figure In the past few years, we have produced a number of 3D- shows how to create a 3D reconstruction model of 24 hpf zebrafishmodels of for the zebrafish atlas as well as spatial patterns of embryo. The 3D reconstruction dataset consists of a modelgene expression, in a range of developmental stages; 24, 36, description (TDRML) file, section images, contour information and 3D surface information.48, 72 hours post-fertilisation (hpf ) [20]. The first step is toacquire raw data. The 3D image datasets for atlas were ZFIN Anatomical Ontology and the Gene Ontology (GO) [22]acquired in both a normal and high resolution from respectively. A reconstruction model also contains metadata© 2011 ACEEE 70DOI: 01.IJIT.01.03. 28
  3. 3. ACEEE Int. J. on Information Technology, Vol. 01, No. 03, Dec 2011that need to be annotated correctly with terms from our as YOLK, DIENCEPHALON and ECTODERM, while weontologies, e.g., the stage of development. Annotation for annotate 3D gene expression domains with standard genereconstruction models has to be done in the reconstruction symbols derived from GO, such as fgf8a and hoxa9a. We software and therefore completes before submitting the annotate all of the 3D models together with the stage ofmodel to the atlas repository. Each 3D reconstruction model developmental. Annotating the datasets with terms derivedis considered as a single instance of data and is described by from standard ontologies provides us the capability toa model description, 3D Reconstruction Markup Language integrate our data with a broad range of external(TDRML), which provides scalability and extensibility, both bioinformatics resources, i.e., ZFIN, Ensembl, ArrayExpressof which are very important for a project that is subject to Atlas. Therefore, mapping the gene expression data fromupdates in order to improve quality of the data. Moreover, GEMS and ArrayExpress Atlas onto the 3D reconstructionTDRML facilitates easy exchange between different models is relatively straightforward. This mapping helpsplatforms. Each model description contains information about answering the question in which anatomical structures inmetadata, section images and annotated domains. Each zebrafish a gene of interest is expressed at a particulardomain is attached with its contour information and 3D developmental stage of the embryo. For example, “Whichsurface data. All of the information described in the model anatomical structures of zebrafish that the gene fgf8a isdescription file will be extracted and subsequently aggregated expressed at the developmental stage of High-pec?”into a relational database management system, i.e., MySQL. The result from mapping is the list of structures whereThis process is realized by submitting the reconstruction the gene of interest is expressed, along with other relatedinstance to the TDR data repository through a web quantitative experimental data such as P-value and theapplication. significant of gene expression. This result will be used later on by the web services to generate proper 3D visualization.B. The Gene Expression Patterns Data Other than providing controlled vocabulary for textual III. VISUALIZATION OF GENE EXPRESSION INannotation, GEMS aims to be an integrative information 3D GRAPHICAL MODELsystem and repository for 3D spatio-temporal patterns ofgene expression. It provides links to related gene expression A. Mapping Gene Expression Data to Geometrydata on other external gene expression resources [6]. GEMS In this context, the gene expression data can be classifiedis capable of organizing and comparing multiple spatial into geometric and non-geometric data. Geometric genepatterns of gene expression at tissue level. GEMS uses the expression data refers to the 3D graphical representation ofsame 3D gene expression patterns image datasets as those the locations where a gene is expressed, which, in our case,for creating reconstruction model for input data. For each 3D are the surface data of 3D gene expression patterns derivedimage dataset, we used the DAOZ to provide common terms from 3D image datasets. This type of gene expression datato describe anatomical features and the developmental stages, can be mapped directly into the 3D visualization scenee.g., list of anatomical structures and developmental stage together with other 3D anatomical structures data from thewhere a particular gene is expressed. We used terms from GO zebrafish atlas. Non-geometric gene expression data, i.e., theto describe the expressed gene in the image datasets. In semantic and quantitative analysis microarray geneaddition, the input image datasets are annotated with imaging expression data, is represented by 3D annotations which canconditions and preparation protocol as well. All data be visualized by using 2D/3D texts and symbols and areannotations have to be done during data submission process. integrated into the 3D scene. Typically, there is a lot ofDue to the lacking of array-based functional genomics data quantitative and semantic gene expression informationin our local resources, we retrieve this information from an compare to the limited area in the visualization scene, thereforeexternal microarray analysis gene expression resource, the pop-up table and dialog box containing links to furtherArrayExpress Atlas [18]. ArrayExpress Atlas is a curated set information on external information resources will be used.of gene expression datasets that are publicly available B. Emphasized Visualizationthrough a web services. The query results from the webservices are the corresponding experiments and p-values for One approach for visualization gene expression data is tothe differentially expressed genes. WikiPathways Atlas hide and emphasize the geometric data of 3D gene expressionMapper [23] is an example of online biological pathway and 3D anatomical structures. Important objects, or even justresource that provides visualization of an integrative pathway a certain object of interest, are highlighted whereas lessinteractions data and gene expression data from ArrayExpress important objects are hidden, removed or reduced inAtlas. perceptibility. Apart from the removal case, this technique can be accomplished using only color, transparency andC. Ontology Based Data Mapping outlines for the visualization. For the visualization of the gene expression data within3D reconstruction model, both data models have to be IV. VISUALIZATION SERVICE ARCHITECTUREintegrated. In the 3D reconstruction models, we annotate 3D In this section we will discuss the service architecture ofanatomical domains with anatomical terms from DAOZ, such our visualization service (Fig. 2). Various information sources© 2011 ACEEE 71DOI: 0.IJIT.01.03. 28
  4. 4. ACEEE Int. J. on Information Technology, Vol. 01, No. 03, Dec 2011are accessed to retrieve the required data. The reconstruction [17]. The result is in Microarray Gene Expression Markupdata repository of 3D atlas data and the 3D patterns of gene Language (MAGE-ML) [25] (Fig. 4). The XML-based formatexpression are stored in a MySQL database server and the has been developed by The Functional Genomics Data (FGED)server file system. In addition, in to facilitate access to our society [26] and Object Management Group (OMG) [27].repositories, TDR and GEMS web services have beenimplemented. These web services can be used to developclient applications providing users a functionality to retrieveand modify the reconstruction and gene expression patternsdata in the repositories. The Bio-Visualization web service isan intermediate component that provides standard interfacesfor retrieving data from local and external web services. Inthis work, we developed web applications that allow users tobrowse and query 3D models in the zebrafish atlas and relatedpatterns of gene expression. The web application uses theBio-Visualization web service to get related microarray datafrom external information sources, i.e. the ArrayExpress Atlas,and deliver an online visualization of gene expression datawithin 3D reconstruction models to end users using Javaapplets.A. Web Services The TDR web service is implemented to enable queryaccess to the 3D reconstruction data in the zebrafish atlasrepository. In similar fashion, the GEMS web service isimplemented to provide access to data in GEMS. Both webservices can be accessed through the Simple Object Accessprotocol (SOAP), and the data structure and availablefunctions are described in Web Service Description Language(WSDL). Both SOAP and WSDL are commonly supportedstandards [24]. With TDR web service, a complete or partial Figure 2. System architecture of visualization service.reconstruction model description can be downloaded in After receiving XML results from all of the underlyingTDRML format (Fig. 3). It provides also interfaces to retrieve web services, the Bio-Visualization web service filters outbinary data of a particular reconstruction model, for instance, the unnecessary information received from the ArrayExpresssection images, contour and surface reconstruction Atlas such as the data that is related to the anatomical partsinformation. Together, a client obtains all necessary data to which do not exist in the 3D reconstruction model of interest.create a 3D visualization of a reconstruction model. GEMS The filtered microarray data will be mapped onto the 3Dweb service provides a query interface for the client to retrieve reconstruction data received from TDR web service and thegene expression data based on annotated information, for extended version of TDRML will be generated. This versioninstance, gene of interest, stage of development and location of TDRML contains not only the original 3D reconstructionwhere the gene is expressed. All the text-based results are data but also contains the quantitative microarray data relatedreturned in XML format. Both web services also allow the each anatomical structure existing in the 3D model of interest.client software to publish information to their underlying data In the end, the output TDRML will be delivered to therepository as well. visualization client, the TDRViewer, over Internet along with The Bio-Visualization web service is implemented as the the related binary data, i.e., section images, 3D contour andintermediate component for a client. The web service uses surface information.TDR and GEMS web services to get access to data in local The Bio-Visualization web service is designed to berepositories. In addition, Bio-Visualization web service also extensible in order to support more external informationuses the ArrayExpress Atlas web service to retrieve related resources in the future. From the client point-of-view, theexperimental array-based gene expression data from the Bio-Visualization web service provides a consistentArrayExpress Repository. The web service allows the user to programming interface for client to retrieve data fromquery for condition-specific based on set of genes by name, heterogeneous sources.organism, and developmental stage. What is returned fromArrayExpress Atlas web service is an XML containing the B. Web Applicationslist of corresponding experimental data related to the gene of The web applications provide query web interfaceinterest, each with P-values and an up/down characterizing allowing users to search for the reconstruction model ofthe significance and direction of differentially expressed genes interest based on anatomical structures, developmental© 2011 ACEEE 72DOI: 01.IJIT.01.03. 28
  5. 5. ACEEE Int. J. on Information Technology, Vol. 01, No. 03, Dec 2011 the visualization to users.Figure 3. An example of TDRML resulted from TDR web service: a complete model description for 3D reconstruction model of spatial gene expression patterns: 14-3-3 in 48 hpf zebrafishembryo. The geometrical gene expression data is outlined with red box. Figure 5. The first page of the web application shows the list of available reconstruction models of atlas and 3D gene expression. Figure 6. The model information page shows links to the related 3D gene expression model and the related whole mount in situFigure 4. An example of XML result from ArrayExpress Atlas web hybridization data in GEMS. More information about eachservice. The first part of the result contains gene information such anatomical structure can also be found by following the link to as GO and Ensembl identifiers, organism and gene name. The external resource, ZFINsecond part contains a list of microarray gene expression data from different experiments. C. The TDRViewerstages (Fig. 5). For each reconstruction model, the web appli- In order to provide 3D interactive visualization over thecations also provide the links, based on the developmental Internet, we have been developing and improving a highlystage, to the related 3D gene expression patterns models and portable 3D reconstruction model viewer, TDRViewer (Fig.the related whole mount in situ hybridization experimental 7). This viewer is an improved version of the atlas viewer wedata from GEMS (Fig. 6). The data access layer of the web developed earlier for the digital atlas of zebrafish development.applications was implemented to adopt the newly introduced TDRViewer is implemented using Java technology and canBio-Visualization web service. The query performed by user be used as a stand-alone application or can be integratedis subsequently executed using the underlying web services. with a web interface as a Java applet allowing online interactiveThe web applications allow users to publish new 3D data of visualization.atlas and gene expression to the corresponding repository as The TDRViewer allows users to visualize our datasets inwell. As the web applications receive all required 3D visual- both 2D and 3D views. The 2D view shows a particular sectionization data from the Bio-Visualization web service, they pass image together with its 2D graphical annotations of thethe data to the client, a Java-based 3D viewer applet to deliver domains of interest; anatomical structures for atlas dataset© 2011 ACEEE 73DOI: 0.IJIT.01.03. 28
  6. 6. ACEEE Int. J. on Information Technology, Vol. 01, No. 03, Dec 2011and the areas where a gene is expressed for spatial gene The viewer uses the available geometric data to construct 3Dexpression data. The user has options to change the zooming scene and overlaying the gene expression data onto the 3Dlevel and the section image. The 3D view provides 3D graphical model of the reconstruction data. As previously visualization in one of the three view modes: contour view, mentioned, the geometric gene expression data can besolid view, and surface view. In the 3D view, user has options visualized directly into the 3D scene while the non-geometricto visualize section plane and section images in 3D scene as data can be visualized as 3D annotations using texts andwell. In this paper, we integrate the TDRViewer with our web symbols. More information on each microarray experimentapplication. After receiving the (extended version of) TDRML and results can be found by following the available link whichfrom the server, the TDRViewer parses all the data and requests redirects user to the ArrayExpress Repository web site.for additional binary data described in TDRML; sectionimages, 3D contour and surface information. Aside from the V. CONCLUSIONSTDRML file, all binary data are compressed on the server We have developed a visualization system that providesbefore sending and decompressed after receiving at the online visualization of gene expression information withinviewer. 3D reconstruction model for the early developmental stages of zebrafish; i.e., 24, 36, 48 and 72 hpf. To support this, we have implemented TDR and GEMS web services that provide interfaces for a client to access our 3D reconstruction and 3D gene expression patterns data in the repositories. We also implemented an intermediate web service, the Bio- Visualization, as a client for retrieving data from local and external web services, i.e., TDR, GEMS and ArrayExpress Atlas. The Bio-Visualization is responsible for filtering unrelated experimental data received from the ArrayExpress Atlas and mapping the result onto the 3D reconstruction model. Mapping all aspects of related gene expression patterns data is accomplished by using an ontology based mapping; using annotated ontology terms to query related gene expression data from local and external resources. The Bio-Visualization web service generates an extended model description, TDRML, which contains not only the originalFigure 7. TDRViewer in the digital atlas of zebrafish: a surface view reconstruction data but also the related gene expression data. of 3D digital atlas of a 48 hpf zebrafish embryo. The web service is designed to be extensible to support more information resources in the future. It also provides a standard data interface to retrieve data from underlying web services. In order to deliver the visualization to end users, a web application is developed. The web application provides a query web interface allowing users to search for the reconstruction model of interest based on anatomical structures and developmental stages. The web application also incorporates the TDRViewer applet allowing users to visualize the graphically combined data interactively over the Internet. The geometric representation of the gene expression data such as the area where the gene is expressed can be directly integrated into a 3D scene with 3D anatomical domains but other gene expression data that do not have a geometric representation (i.e. microarray data) can be visualized as 3D annotations. To limit the amount of annotated information in the 3D scene, a pop-up menu or Figure 8. A surface visualization with a 3D section image of gene dialog box containing links to further information on externalexpression patterns: 14-3-3 gamma2 in a 48 hpf embryo; the gene information resources will be used. In this way, users are able expression is annotated in white together with some reference to derive relations between the spatial information of 3D anatomical structures. Related microarray gene expression data on reconstruction models and patterns of gene expression in a the gene 14-3-3 from ArrayExpress Atlas are annotated in the lower left corner of the 3D scene. This information indicates the 3D context.anatomical structures that this gene is expressed and how much it is expressed. The annotation also provides links to all related experimental data in the ArrayExpress Atlas.© 2011 ACEEE 74DOI: 01.IJIT.01.03. 28
  7. 7. ACEEE Int. J. on Information Technology, Vol. 01, No. 03, Dec 2011 ACKNOWLEDGMENTS [10] D. Maglott, J. Ostell, K. D. Pruitt, and T. Tatusova, “Entrez Gene: gene-centered information at NCBI,” Nucleic acids research, The authors wish to express their gratitude to Gerda vol. 39(suppl 1), pp. D52, 2011.Lamers, Esther Dondorp, Rebecca Schoon, Laura Bertens, [11] P. Flicek, et al., “Ensembl 2011,” Nucleic acids research, vol.Monique Welten, Willemijn Spoor and Aimy Sels for 39(suppl 1), pp. D800, 2011.providing the experimental data and creating 3D [12] “The Edinburgh Mouse Atlas Project.” Available from: http:/reconstruction models from atlas and 3D gene expression /genex.hgu.mrc.ac.uk.patterns datasets. This work is partially supported by [13] “The Edinburgh Mouse Gene Expression Atlas.” AvailableNetherlands’ council for Scientific Research (NWO) and a from: http://genex.hgu.mrc.ac.uk. [14] M. Hawrylycz, et al., “Digital Atlasing and Standardizationpersonal grant from the Ministry of Science and Technology, in the Mouse Brain,” PLoS Comput Biol, vol. 7(2), pp. e1001065,Thai Government. 2011. [15] G. H. Weber, et al., “Visual exploration of three-dimensional REFERENCES gene expression using physical views and linked abstract views,” IEEE IEEE/ACM Transactions on Computational Biology and[1] J. Streicher, M. Donat, B. Strauss, R. Sporle, and G. Muller, Bioinformatics, pp. 296-309, 2007.“Computer-Based Three-Dimensional Visualization of [16] O. R¸bel, et al. “PointCloudXplore: Visual analysis of 3DDevelopmental Gene Expression,” Nature Genetics, vol. 25(2), pp. gene expression data using physical views and parallel coordinates,”147 - 52, 2000. 2006. Citeseer.[2] F. J. Verbeek and P. J. Boon, “High-resolution 3D [17] H. Parkinson, et al., “ArrayExpress update-from an archivereconstruction from serial sections: microscope instrumentation, of functional genomics experiments to the atlas of gene expression,”software design, and its implementations,” in Three-Dimensional Nucleic acids research, vol. 37(suppl 1), pp. D868, 2009.and Multidimensional Microscopy: Image Acquisition and [18] “ArrayExpress: Gene Expression Atlas.” Available from: http:/Processing IX, J.-A. Conchello, C.J. Cogswell, and T. Wilson, /www.ebi.ac.uk/gxa/.Editors. 2002, SPIE: San Jose, CA, USA. pp. 65-76. [19] C. A. Ball, et al., “Submission of microarray data to public[3] F. J. Verbeek, P. J. Boon, H. Sloetjes, R. van der Velde, and N. repositories,” PLoS Biology, vol. 2(9), pp. e317, 2004.Vos, “Visualization of complex data sets over Internet: 2D and 3D [20] C. B. Kimmel, W. W. Ballard, S. R. Kimmel, B. Ullmann, andvisualization of the 3D digital atlas of zebrafish development,” in T. F. Schilling, “Stages of embryonic development of the zebrafish,”Internet Imaging III, G.B. Beretta and R. Schettini, Editors. 2001, Am. J. Anat., vol. 203(3), pp. 253-310, 1995.SPIE: San Jose, CA, USA. pp. 20-29. [21] M. Belmamoune and F. J. Verbeek, “Developmental Anatomy[4] A. Butte, “The use and analysis of microarray data,” Nature Ontology of Zebrafish: an Integrative semantic framework,” Journalreviews drug discovery, vol. 1(12), pp. 951-960, 2002. of Integrative Bioinformatics, vol. 4(3), pp. 65, 2007.[5] D. E. Bassett, M. B. Eisen, and M. S. Boguski, “Gene [22] M. Ashburner, et al., “Gene Ontology: tool for the unificationexpression informaticsóit’s all in your mine,” Nature Genetics, vol. of biology,” Nature Genetics, vol. 25(1), pp. 25-29, 2000.21, pp. 51-55, 1999. [23] T. Kelder, et al., “Mining Biological Pathways Using[6] M. Belmamoune and F. J. Verbeek, “Data Integration for WikiPathways Web Services,” PLoS ONE, vol. 4(7), pp. e6447,Spatio-Temporal Patterns of Gene Expression of Zebrafish 2009.development: the GEMS database,” Journal of Integrative [24] “Web Services Architecture.” Available from: http://Bioinformatics, vol. 5(2), pp. 92, 2008. www.w3.org/TR/2004/NOTE-ws-arch-20040211/.[7] M. C. M. Welten, et al., “ZebraFISH: Fluorescent In Situ [25] P. T. Spellman, et al., “Design and implementation ofHybridization Protocol and Three-Dimensional Imaging of Gene microarray gene expression markup language (MAGE-ML),”Expression Patterns,” Zebrafish, vol. 3(4), pp. 465-476, 2006. Genome biology, vol. 3(9), pp. research0046, 2002.[8] J. Sprague, et al., “The Zebrafish Information Network: the [26] “The Functional Genomics Data Society.” Available from:zebrafish model organism database,” Nucleic acids research, vol. http://www.mged.org/.34(suppl 1), pp. D581, 2006. [27] “Object Management Group.” Available from: http://[9] A. Brazma, et al., “ArrayExpress-a public repository for www.omg.org/.microarray gene expression data at the EBI,” Nucleic acids research,vol. 31(1), pp. 68, 2003.© 2011 ACEEE 75DOI: 0.IJIT.01.03. 28

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