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The Sterolgene v0 cDNA microarray: a systemic approach to studies of cholesterol homeostasis and drug metabolism.

Rezen T, Juvan P, Fon Tacer K, Kuzman D, Roth A, Pompon D, Aggerbeck LP, Meyer UA, Rozman D - BMC Genomics (2008)

Bottom Line: Additionally, the performance of the Sterolgene v0 was compared to the two commercial high density microarray platforms: the Agilent cDNA (G4104A) and the Affymetrix MOE430A GeneChip.Together with its next generations the Sterolgene microarrays represent original and dedicated tools enabling focused and cost effective studies of cholesterol homeostasis and drug metabolism.These microarrays have the potential of being further developed into screening or diagnostic tools.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for Functional Genomics and Bio-Chips, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Zaloska 4, SI-1000 Ljubljana, Slovenia. tadeja.rezen@mf.uni-lj.si

ABSTRACT

Background: Cholesterol homeostasis and xenobiotic metabolism are complex biological processes, which are difficult to study with traditional methods. Deciphering complex regulation and response of these two processes to different factors is crucial also for understanding of disease development. Systems biology tools as are microarrays can importantly contribute to this knowledge and can also discover novel interactions between the two processes.

Results: We have developed a low density Sterolgene v0 cDNA microarray dedicated to studies of cholesterol homeostasis and drug metabolism in the mouse. To illustrate its performance, we have analyzed mouse liver samples from studies focused on regulation of cholesterol homeostasis and drug metabolism by diet, drugs and inflammation. We observed down-regulation of cholesterol biosynthesis during fasting and high-cholesterol diet and subsequent up-regulation by inflammation. Drug metabolism was down-regulated by fasting and inflammation, but up-regulated by phenobarbital treatment and high-cholesterol diet. Additionally, the performance of the Sterolgene v0 was compared to the two commercial high density microarray platforms: the Agilent cDNA (G4104A) and the Affymetrix MOE430A GeneChip. We hybridized identical RNA samples to the commercial microarrays and showed that the performance of Sterolgene is comparable to commercial arrays in terms of detection of changes in cholesterol homeostasis and drug metabolism.

Conclusion: Using the Sterolgene v0 microarray we were able to detect important changes in cholesterol homeostasis and drug metabolism caused by diet, drugs and inflammation. Together with its next generations the Sterolgene microarrays represent original and dedicated tools enabling focused and cost effective studies of cholesterol homeostasis and drug metabolism. These microarrays have the potential of being further developed into screening or diagnostic tools.

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Scatterplots of log2 ratios between Sterolgene, Agilent and Affymetrix. Scatterplots of log2 ratios of genes that are present in Agilent and Sterolgene arrays (A), and Affymetrix and Sterolgene arrays (B). Values from both experiments performed for each cross-platform comparison were combined in a single plot.
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Figure 5: Scatterplots of log2 ratios between Sterolgene, Agilent and Affymetrix. Scatterplots of log2 ratios of genes that are present in Agilent and Sterolgene arrays (A), and Affymetrix and Sterolgene arrays (B). Values from both experiments performed for each cross-platform comparison were combined in a single plot.

Mentions: Low correspondence in differential expression may be due to the fact that of 54 genes in common only 20 showed significant signal on the Agilent arrays. For these genes we calculated Pearson's product moment correlation coefficient between log2 ratios in both experiments. Figure 5A shows a scatterplot of that data. Though the correspondence in differential expression is low, we observed a significant correlation between the platforms (r = 0.508, p = 0.001, N = 40), which is comparable to correlations reported by other cross-platform comparison studies [12,17-19].


The Sterolgene v0 cDNA microarray: a systemic approach to studies of cholesterol homeostasis and drug metabolism.

Rezen T, Juvan P, Fon Tacer K, Kuzman D, Roth A, Pompon D, Aggerbeck LP, Meyer UA, Rozman D - BMC Genomics (2008)

Scatterplots of log2 ratios between Sterolgene, Agilent and Affymetrix. Scatterplots of log2 ratios of genes that are present in Agilent and Sterolgene arrays (A), and Affymetrix and Sterolgene arrays (B). Values from both experiments performed for each cross-platform comparison were combined in a single plot.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2262072&req=5

Figure 5: Scatterplots of log2 ratios between Sterolgene, Agilent and Affymetrix. Scatterplots of log2 ratios of genes that are present in Agilent and Sterolgene arrays (A), and Affymetrix and Sterolgene arrays (B). Values from both experiments performed for each cross-platform comparison were combined in a single plot.
Mentions: Low correspondence in differential expression may be due to the fact that of 54 genes in common only 20 showed significant signal on the Agilent arrays. For these genes we calculated Pearson's product moment correlation coefficient between log2 ratios in both experiments. Figure 5A shows a scatterplot of that data. Though the correspondence in differential expression is low, we observed a significant correlation between the platforms (r = 0.508, p = 0.001, N = 40), which is comparable to correlations reported by other cross-platform comparison studies [12,17-19].

Bottom Line: Additionally, the performance of the Sterolgene v0 was compared to the two commercial high density microarray platforms: the Agilent cDNA (G4104A) and the Affymetrix MOE430A GeneChip.Together with its next generations the Sterolgene microarrays represent original and dedicated tools enabling focused and cost effective studies of cholesterol homeostasis and drug metabolism.These microarrays have the potential of being further developed into screening or diagnostic tools.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for Functional Genomics and Bio-Chips, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Zaloska 4, SI-1000 Ljubljana, Slovenia. tadeja.rezen@mf.uni-lj.si

ABSTRACT

Background: Cholesterol homeostasis and xenobiotic metabolism are complex biological processes, which are difficult to study with traditional methods. Deciphering complex regulation and response of these two processes to different factors is crucial also for understanding of disease development. Systems biology tools as are microarrays can importantly contribute to this knowledge and can also discover novel interactions between the two processes.

Results: We have developed a low density Sterolgene v0 cDNA microarray dedicated to studies of cholesterol homeostasis and drug metabolism in the mouse. To illustrate its performance, we have analyzed mouse liver samples from studies focused on regulation of cholesterol homeostasis and drug metabolism by diet, drugs and inflammation. We observed down-regulation of cholesterol biosynthesis during fasting and high-cholesterol diet and subsequent up-regulation by inflammation. Drug metabolism was down-regulated by fasting and inflammation, but up-regulated by phenobarbital treatment and high-cholesterol diet. Additionally, the performance of the Sterolgene v0 was compared to the two commercial high density microarray platforms: the Agilent cDNA (G4104A) and the Affymetrix MOE430A GeneChip. We hybridized identical RNA samples to the commercial microarrays and showed that the performance of Sterolgene is comparable to commercial arrays in terms of detection of changes in cholesterol homeostasis and drug metabolism.

Conclusion: Using the Sterolgene v0 microarray we were able to detect important changes in cholesterol homeostasis and drug metabolism caused by diet, drugs and inflammation. Together with its next generations the Sterolgene microarrays represent original and dedicated tools enabling focused and cost effective studies of cholesterol homeostasis and drug metabolism. These microarrays have the potential of being further developed into screening or diagnostic tools.

Show MeSH
Related in: MedlinePlus