Toxicogenomics using microarray technology offers the ability to conduct large-scale detections and quantifications of mRNA transcripts, particularly those associated with alterations in mRNA stability or gene regulation. In this study, we developed the HazChem Human Array V2 using the Agilent Sure-...
Toxicogenomics using microarray technology offers the ability to conduct large-scale detections and quantifications of mRNA transcripts, particularly those associated with alterations in mRNA stability or gene regulation. In this study, we developed the HazChem Human Array V2 using the Agilent Sure-Print technology-based custom array, which is expected to facilitate the identification of environmental toxicants. The array was manufactured using 600 VOCs and PAHs-specific genes identified in previous studies. In order to evaluate the viability of the manufactured HazChem human array V2, we analyzed the gene expression profiles of 9 environmental toxicants (6 VOCs chemicals and 3 PAHs chemicals). As a result, nine toxicants were separated into two chemical types-VOCs and PAHs. After the chip validations with VOCs and PAHs, we conducted an expression profiling comparison of additional chemical groups (POPs and EDCs) using data analysis methods such as hierarchical clustering, 1-way ANOVA, SAM, and PCA. We selected 58 genes that could be classified into four chemical types via statistical methods. Additionally, we selected 63 genes that evidenced significant alterations in expression with all 13 environmental toxicants. These results suggest that the HazChem Human Array V2 will expedite the development of a screening system for environmentally hazardous materials at the level of toxicogenomics in the future.
Toxicogenomics using microarray technology offers the ability to conduct large-scale detections and quantifications of mRNA transcripts, particularly those associated with alterations in mRNA stability or gene regulation. In this study, we developed the HazChem Human Array V2 using the Agilent Sure-Print technology-based custom array, which is expected to facilitate the identification of environmental toxicants. The array was manufactured using 600 VOCs and PAHs-specific genes identified in previous studies. In order to evaluate the viability of the manufactured HazChem human array V2, we analyzed the gene expression profiles of 9 environmental toxicants (6 VOCs chemicals and 3 PAHs chemicals). As a result, nine toxicants were separated into two chemical types-VOCs and PAHs. After the chip validations with VOCs and PAHs, we conducted an expression profiling comparison of additional chemical groups (POPs and EDCs) using data analysis methods such as hierarchical clustering, 1-way ANOVA, SAM, and PCA. We selected 58 genes that could be classified into four chemical types via statistical methods. Additionally, we selected 63 genes that evidenced significant alterations in expression with all 13 environmental toxicants. These results suggest that the HazChem Human Array V2 will expedite the development of a screening system for environmentally hazardous materials at the level of toxicogenomics in the future.
* AI 자동 식별 결과로 적합하지 않은 문장이 있을 수 있으니, 이용에 유의하시기 바랍니다.
문제 정의
The principal objective of this study was the biomarker identification of environmental toxicant groups and common expression gene discovery in environmental chemical-treated cells using a manufactured HazChem Human array V2. In this study, we assessed 6 of VOCs, 3 PAHs, 2 POPs and 2 EDCs 아lemi- cals.
The principal objective of this study was to validate the HazChem Human Array V2 on environmental toxicants. The HazChem Human Array V2 design was based on VOCs and PAHs groups of environmental toxicants.
제안 방법
Firstly, we assessed the whole geexpression profile, and used the data for a definitive classification of VOCs and PAHs (Figure 1). This indicates that the gene contents on HazChem human array V2 are appropriate for the classification of the two groups.
We found 63 common expressed genes associated with all types of environmental toxicants, on the basis of the gene expression profiles and genetic distances (Figure 3). Furthermore, different analysis methods such as 1-way ANOVA, SAM, and PCA were also utilized for the validation and classification of the HazChem Hman Array chip.
humans7. In this study, we used a HazChem human array to identify the significantly differentially expressed genes induced by several chemicals in human cell lines. The results of our microarray data analysis demonstrated differentially expressed gene patterns resulting from exposure to VOCs (benzene, o-xylene, toluene, ethylbenzene, dichloromethane, trichloroethylene), PAHs (dibenzo [a, h] anthracene, 3-methylchlo- lanthrene, benzo[k]fluoranthene), POPs (chlordane, toxaphene), and EDCs (bisphenol A, 17b-estradiol) in a human cell line.
The hybridized slides were scanned with an Axon Instruments GenePix 4000B scanner and the scanned images were analyzed using the GenePix Pro 5.1 program (Axon, CA) and GeneSpring GX 7.3.1 (Agilent Technologies, CA). Spots that were adjudged as substandard via the visual examination of each slide were flagged and excluded from further analysis.
데이터처리
Classification of two chemical group using genes selected by 1-way ANOVA. 135 genes selected by statistical method, 1-way ANOVA (p-value cutoff 0.05, multiple testing correction: Benjamini and Hochberg False Discovery Rate). Expression profile of these genes more clearly clustered to two chemical types relative to the total gene expression profile.
Classification of 4 chemical groups using gene selected by 1-way ANOVA. 58 genes selected by statistical method, 1-way ANOVA (p-value cutoff 0.05, multiple testing correction: Benjamini and Hochberg False Discovery Rate). 13 chemicals accurately classified to 4 chemical types using 58 selected genes.
Figure 4. Classification of 4 chemical groups using gene selected by 1-way ANOVA. 58 genes selected by statistical method, 1-way ANOVA (p-value cutoff 0.
Figure 2. Classification of two chemical group using genes selected by 1-way ANOVA. 135 genes selected by statistical method, 1-way ANOVA (p-value cutoff 0.
This indicates that the gene contents on HazChem human array V2 are appropriate for the classification of the two groups. In order to conduct a more accurate classification, 135 genes were selected by the statistical method, 1-way ANOVA (p-value cutoff 0.05, mItiple testing correction: Ben- jamini and Hochberg False Discovery Rate). The expression profiles of these genes were more clearly clustered to two chemical types than the total gene expression profile.
analysis. We selected 58 genes that could be classified into four chemical types using statistical methods such as 1- way ANOVA. Genes from all genes with statistically significant differences when grouped by chemical type; parametric test.
성능/효과
In this study, we used a HazChem human array to identify the significantly differentially expressed genes induced by several chemicals in human cell lines. The results of our microarray data analysis demonstrated differentially expressed gene patterns resulting from exposure to VOCs (benzene, o-xylene, toluene, ethylbenzene, dichloromethane, trichloroethylene), PAHs (dibenzo [a, h] anthracene, 3-methylchlo- lanthrene, benzo[k]fluoranthene), POPs (chlordane, toxaphene), and EDCs (bisphenol A, 17b-estradiol) in a human cell line. In this study, the data were compiled from authentic sHees through the added or changed chemicals from the previous data.
참고문헌 (17)
Wogan, G. N., Hecht, S. S., Felton, J. S., Conney, A. H. & Loeb, L. A. Environmental and chemical carcinogenesis. Semin Cancer Biol 14:473-486 (2004)
Teuschler, L. K., Groten, J. P., Hertzberg, R. C., Mumtaz, M. M. & Rice, G. Environmental chemical mixtures risk assessment: current approaches and emerging issues. Comments on Toxicology 7:453-493 (2001)
Witsman, F. A. et al. Toxicity of chemical mixtures: proteomic analysis of persisting liver and kidney pro-tein alterations induced by repeated exposure of rats to JP-8 jet fuel vapor. Electrophoresis 21:2138-2147 (2000)
Nuwaysir, E. F., Bittmer, M., Trent, J., Barrett, J. C. & Afshari, C. A. Microarray and toxicology: The advent of toxicogenomics. Mol Calcinog 24:153-159 (1999)
Chung, H. et al. Comprehensive analysis of differential gene expression profiles on carbon tetrachlorideinduced rat liver injury and regeneration. Toxicol Appl Pharmacol 206:27-42 (2004)
Oda, H. et al. Microarray analysis of the genes induced by tetracycline-regulated expression of NDRF/NeuroD2 in P19 cells. Biochem Biophys Res Commun 335:458-468 (2005)
Powell, C. L. et al. Phenotypic anchoring of acetaminophen-induced oxidative stress with gene expression profiles in rat liver. Toxicol Sci 93:213-222 (2006)
Waters, M. et al. Systems toxicology and the Chemical Effects in BiologicalSystems (CEBS) knowledgebase. EHP Toxicogenomics 111:15-28 (2003)
Fostel, J. et al. Chemical effects in biological systemsdata dictionary (CEBS-DD): a compendium of terms for the capture and integration of biological study design description, conventional phenotypes, and omics data. Toxicol Sci 88:585-601 (2005)
De Rosa, C. T., El-Masri, H. A., Pohl, H., Cibulas, W. & Mumtaz, M. M. Implications of chemical mixtures in public health pratice. J Toxicol Environ Health Part B Crit Rev 7:339-350 (2004)
Sarma, S. N., Kim, Y. J. & Ryu, J. C. Differential gene expression profiling in human promyelocytic leukemia cells treated with benzene and ethylbenzene. Mol Cell Toxicol 4:267-277 (2008)
※ AI-Helper는 부적절한 답변을 할 수 있습니다.