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      Microarray platform consistency is revealed by biologically functional analysis of gene expression profiles

      research-article
      1 , 2 , 2 , 2 , 1 ,
      BMC Bioinformatics
      BioMed Central
      Sixth Annual MCBIOS Conference. Transformational Bioinformatics: Delivering Value from Genomes
      20-21 February 2009

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          Abstract

          Background

          Several different microarray platforms are available for measuring gene expression. There are disagreements within the microarray scientific community for intra- and inter-platform consistency of these platforms. Both high and low consistencies were demonstrated across different platforms in terms of genes with significantly differential expression. Array studies for gene expression are used to explore biological causes and effects. Therefore, consistency should eventually be evaluated in a biological setting to reveal the functional differences between the examined samples, not just a list of differentially expressed genes (DEG). In this study, we investigated whether different platforms had a high consistency from the biologically functional perspective.

          Results

          DEG data without filtering the different probes in microarrays from different platforms generated from kidney samples of rats treated with the kidney carcinogen, aristolochic acid, in five test sites using microarrays from Affymetrix, Applied Biosystems, Agilent, and GE health platforms (two sites using Affymetrix for intra-platform comparison) were input into the Ingenuity Pathway Analysis (IPA) system for functional analysis. The functions of the DEG lists determined by IPA were compared across the four different platforms and two test sites for Affymetrix platform. Analysis results showed that there is a very high level of consistency between the two test sites using the same platform or among different platforms. The top functions determined by the different platforms were very similar and reflected carcinogenicity and toxicity of aristolochic acid in the rat kidney.

          Conclusion

          Our results demonstrate that highly consistent biological information can be generated from different microarray platforms.

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          Most cited references15

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          Urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi)

          Chinese-herb nephropathy is a progressive form of renal fibrosis that develops in some patients who take weight-reducing pills containing Chinese herbs. Because of a manufacturing error, one of the herbs in these pills (Stephania tetrandra) was inadvertently replaced by Aristolochia fangchi, which is nephrotoxic and carcinogenic. The diagnosis of a neoplastic lesion in the native urinary tract of a renal-transplant recipient who had Chinese-herb nephropathy prompted us to propose regular cystoscopic examinations and the prophylactic removal of the native kidneys and ureters in all our patients with end-stage Chinese-herb nephropathy who were being treated with either transplantation or dialysis. Surgical specimens were examined histologically and analyzed for the presence of DNA adducts formed by aristolochic acid. All prescriptions written for Chinese-herb weight-reducing compounds during the period of exposure (1990 to 1992) in these patients were obtained, and the cumulative doses were calculated. Among 39 patients who agreed to undergo prophylactic surgery, there were 18 cases of urothelial carcinoma (prevalence, 46 percent; 95 percent confidence interval, 29 to 62 percent): 17 cases of carcinoma of the ureter, renal pelvis, or both and 1 papillary bladder tumor. Nineteen of the remaining patients had mild-to-moderate urothelial dysplasia, and two had normal urothelium. All tissue samples analyzed contained aristolochic acid-related DNA adducts. The cumulative dose of aristolochia was a significant risk factor for urothelial carcinoma, with total doses of more than 200 g associated with a higher risk of urothelial carcinoma. The prevalence of urothelial carcinoma among patients with end-stage Chinese-herb nephropathy (caused by aristolochia species) is a high.
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            Evaluation of gene expression measurements from commercial microarray platforms.

            P. Tan (2003)
            Multiple commercial microarrays for measuring genome-wide gene expression levels are currently available, including oligonucleotide and cDNA, single- and two-channel formats. This study reports on the results of gene expression measurements generated from identical RNA preparations that were obtained using three commercially available microarray platforms. RNA was collected from PANC-1 cells grown in serum-rich medium and at 24 h following the removal of serum. Three biological replicates were prepared for each condition, and three experimental replicates were produced for the first biological replicate. RNA was labeled and hybridized to microarrays from three major suppliers according to manufacturers' protocols, and gene expression measurements were obtained using each platform's standard software. For each platform, gene targets from a subset of 2009 common genes were compared. Correlations in gene expression levels and comparisons for significant gene expression changes in this subset were calculated, and showed considerable divergence across the different platforms, suggesting the need for establishing industrial manufacturing standards, and further independent and thorough validation of the technology.
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              Rat toxicogenomic study reveals analytical consistency across microarray platforms

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                Author and article information

                Conference
                BMC Bioinformatics
                BMC Bioinformatics
                BioMed Central
                1471-2105
                2009
                8 October 2009
                : 10
                : Suppl 11
                : S12
                Affiliations
                [1 ]Division of Genetic and Reproductive Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, 3900 NCTR Rd., Jefferson, Arkansas 72079, USA
                [2 ]Division of Systems Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, 3900 NCTR Rd., Jefferson, Arkansas 72079, USA
                Article
                1471-2105-10-S11-S12
                10.1186/1471-2105-10-S11-S12
                3226184
                19811677
                39ae9a3a-3698-4bdb-bc50-c748cc8edd98
                Copyright ©2009 Li et al; 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.

                Sixth Annual MCBIOS Conference. Transformational Bioinformatics: Delivering Value from Genomes
                Starkville, MS, USA
                20-21 February 2009
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                Proceedings

                Bioinformatics & Computational biology
                Bioinformatics & Computational biology

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