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Download.Cse.Ucsc.Edu/Goldenpath/ Knowngene Mm7/Database/ Refgene All Mrna Knowntoensembl BMC Genomics BioMed Central Methodology article Open Access Comparison of gene coverage of mouse oligonucleotide microarray platforms Ricardo A Verdugo and Juan F Medrano* Address: Department of Animal Science, University of California Davis, One Shields Avenue, Davis, CA 95616-8521, USA Email: Ricardo A Verdugo - [email protected]; Juan F Medrano* - [email protected] * Corresponding author Published: 21 March 2006 Received: 24 September 2005 Accepted: 21 March 2006 BMC Genomics2006, 7:58 doi:10.1186/1471-2164-7-58 This article is available from: http://www.biomedcentral.com/1471-2164/7/58 © 2006Verdugo and Medrano; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: The increasing use of DNA microarrays for genetical genomics studies generates a need for platforms with complete coverage of the genome. We have compared the effective gene coverage in the mouse genome of different commercial and noncommercial oligonucleotide microarray platforms by performing an in-house gene annotation of probes. We only used information about probes that is available from vendors and followed a process that any researcher may take to find the gene targeted by a given probe. In order to make consistent comparisons between platforms, probes in each microarray were annotated with an Entrez Gene id and the chromosomal position for each gene was obtained from the UCSC Genome Browser Database. Gene coverage was estimated as the percentage of Entrez Genes with a unique position in the UCSC Genome database that is tested by a given microarray platform. Results: A MySQL relational database was created to store the mapping information for 25,416 mouse genes and for the probes in five microarray platforms (gene coverage level in parenthesis): Affymetrix430 2.0 (75.6%), ABI Genome Survey (81.24%), Agilent (79.33%), Codelink (78.09%), Sentrix (90.47%); and four array-ready oligosets: Sigma (47.95%), Operon v.3 (69.89%), Operon v.4 (84.03%), and MEEBO (84.03%). The differences in coverage between platforms were highly conserved across chromosomes. Differences in the number of redundant and unspecific probes were also found among arrays. The database can be queried to compare specific genomic regions using a web interface. The software used to create, update and query the database is freely available as a toolbox named ArrayGene. Conclusion: The software developed here allows researchers to create updated custom databases by using public or proprietary information on genes for any organisms. ArrayGene allows easy comparisons of gene coverage between microarray platforms for any region of the genome. The comparison presented here reveals that the commercial microarray Sentrix, which is based on the MEEBO public oligoset, showed the best mouse genome coverage currently available. We also suggest the creation of guidelines to standardize the minimum set of information that vendors should provide to allow researchers to accurately evaluate the advantages and disadvantages of using a given platform. Page 1 of 14 (page number not for citation purposes) BMC Genomics 2006, 7:58 http://www.biomedcentral.com/1471-2164/7/58 Background choosing the platform that best fits their needs. We have The wide use of DNA microarrays to query expression of developed a platform for microarray annotation that not genes has created the need for updated, consistent and only provides gene annotations for probes but also meaningful annotations on the probes included in the genomic positions for tested genes in the mouse genome. microarrays. We refer to gene annotation as a recognizable Coverage comparisons can be obtained for any genomic label or gene id identifying the gene that is targeted by a region of the last available mouse assembly build. The given probe. Gene ids should be stable, widely used and level of coverage of five whole mouse genome microarrays allow reliable associations among genomic databases. and four oligosets was compared in the present study. Several microarray annotation systems are available for Microarrays and oligosets will be referenced here by the investigators, aiming to address specific user demands. short name provided in Table 3. The results were stored in For instance, the KARMA [1] web server provides periodi- a relational database that can readily be queried for cover- cally updated gene annotations of Keck arrays [2] and age comparisons based on genome position. Figure 1 Affymetrix® GeneChips® [3], and can also annotate user- shows a flowchart diagram for the databases and methods provided lists of accession numbers for pair-wise compar- used for the annotation system and for querying gene cov- isons, even for different species. However, providing a erage comparisons. gene list is not always a straight forward process given the large heterogeneity in the format that vendors provide Results sequence identifiers for probes. For instance, one platform Number of genes in the genome can include identifiers in a Genbank header format such The total number of genes in the genome was defined as as GB|AY073000.1|AAL60663.1 and others may include the number of Entrez Genes with a unique genomic posi- different types of ids separated by commas or some other tion at the UCSC Genome Browser Database [14] (see character within a single column. In addition, different methods). A total of 198,155 mapped sequences from the sequence identifiers in several columns may be provided Known Gene, RefGene, and mRNA tracks were associated by vendors and choosing only one of them may not be the with Entrez Genes. A total of 521 genes could not be used best solution. The Resourcerer database [4] tackles this because they are located in unordered scaffolds in Build problem by pre-computing gene annotations on a more 35.1 of the mouse genome assembly. Multiple sequence exhaustive list of microarrays and oligosets for a number alignments in the genomes were found for a total of 1,766 of species [5]. This database is centered on 'tentative con- sequences. For example, the M10062 cDNA aligns with sensus' (TC) sequences which are used as gene definitions. chromosomes 1, 2, 3, 4, 6, 10, 11, 13, 15, 17, 19, X, and TCs group EST sequences that can be aligned and clus- Un_random (not chromosome assigned contigs) chro- tered in distinct groups, and these are periodically mosomes. This cDNA is identified as the Iap gene in the updated as new ESTs from GenBank become available. Entrez Gene database. This is a retrotransposon that can Functional annotations on these TCs generate the Gene be found in several chromosomes and does not have a Indices resource available from the TGI website [6]. TCs unique position. Genes like this, and other not so extreme allow for cross species comparisons through the Tentative cases, cannot be considered in region-specific coverage Orthologue Groups (TOGs) database. However, Gene comparisons and were therefore discarded. Table 2 shows Indices are not stable and cross referencing to other the number of genes that could be assigned to specific genomic databases is not easy. A different approach has position in the genome in each of the source files. The file been taken by Mattes[7] who created a set of Perl scripts Mm.gb_cid_lid in Table 1 was used to incorporate associ- that use UniGene and LocusLink as gene identifiers, pro- ations between sequences and Unigene ids in the genexref viding a more universal gene definition that can be cross table. Although we do not use Unigene annotations of referenced with other databases. Unfortunately, the recent probes to identify the targeted genes (see discussion sec- shift of NCBI from LocusLink to the Entrez Gene database tion for explanation) this allowed us to associate Entrez format [8] has limited the functionality of these scripts Gene ids with EST accession numbers, which are com- and rendered them obsolete. The DRAGON [9] database monly used in microarray genes lists. A total of 25,416 [10,11], and the DAVID [12] software [13] provide web genes could be found having a unique position in the based services of gene annotation with similar objectives. August 2005 mouse genome assembly (Build 35.1). The None of them, however, allows for chromosome or distribution of these genes in the genome is shown in Fig- genomic-region specific comparisons of gene coverage. ure 2. The objective of this study was to compare gene coverage Microarrays probe annotations from currently available whole mouse genome microar- The Resourcerer database provides gene annotations for rays for any region of the genome. We only used the infor- most of the available microarrays and oligosets for mouse mation about probes provided to researchers by vendors and other organisms [4]. However, database updates are before the purchase of a microarray for the purpose of done at four-month intervals, and in our experience, gene Page 2 of 14 (page number not for citation purposes) BMC Genomics 2006, 7:58 http://www.biomedcentral.com/1471-2164/7/58 FlowchartFigure 1 diagram for the construction and query of the ArrayGene and Aligndb databases Flowchart diagram for the construction and query of the ArrayGene and Aligndb databases. Perl scripts are used to parse input files from other databases and upload the processed information to the ArrayGene and Aligndb databases. The ma_compare CGI (Common Gateway Interface) script written in Perl is used to process queries through the web and produce online reports for gene coverage. Page 3 of 14 (page number not for citation purposes) BMC Genomics 2006, 7:58 http://www.biomedcentral.com/1471-2164/7/58 annotations change periodically and many Entrez Gene dant being the Sigma platform (1.08 probes per gene on ids in the Resourcerer annotations are obsolete.
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