There has been growing interest in investigating epigenetic mechanisms as related to regulation of gene expression. DNA methylation and histone modifications are two types of epigenetic modifications that are highly correlated with regulation of gene expression, genome imprinting and gene silencing. Although epigenomic research has added to our understanding of biological phenomena, little work has been done to establish statistical methods that exploit the relationship between epigenetic modifications and gene expression. Here, we discuss the individual statistical hypotheses for differential expression, methylation and chromatin modification, and then suggest a simple statistical approach that integrates the results from each individual epigenomic experiment.
KeywordsEpigenetics Epigenomics Methylation Histone modification Tiling array Statistical bioinformatics ANOVA model Meta-analysis
Unable to display preview. Download preview PDF.
- Benjamini, Y. and Hochberg Y., 1995. Controlling the false discovery rate: a practical and powerful approach to multiple testing. Journal of the Royal Statistical Society, Series B 57:289–300.Google Scholar
- Black, M. A., 2002. Statistical issues in the design and analysis of spotted microarray experiments. Ph.D. Thesis, Department of Statistics, Purdue University, West Lafayette, IN, USA.Google Scholar
- Dudoit, S., Yang, Y. H., Speed, T. P. and Callow, M. J., 2002. Statistical methods for identifying differentially expressed genes in replicated cDNA microarray experiments. Statistica Sinica 12(1): 111–139.Google Scholar
- Emanuelsson, O., Nagalakshmi, U., Zheng D., Rozowsky, J. S., Urban, A. E., Du, J., Lian, Z., Stolc, V., Weissman, S., Snyder, M. and Gerstein, M. B., 2007. Assessing the performance of different high-density tiling microarray strategies for mapping transcribed regions of the human genome. Genome Research 17:886–897.PubMedCrossRefGoogle Scholar
- Finnegan, J.E., Kovac, K.A., Jaligot, E., Sheldon, C.C., Peacock, W.J. and Dennis, E.S., 2005. The downregulation of FLOWERING LOCUS C (FLC) expression in plants with low levels of DNA methylation and by vernalization occurs by distinct mechanisms Plant Journal 44(3): 420–432, doi: 10.1111/j.1365-313X.2005.02541.xCrossRefGoogle Scholar
- Gibbons, J. D., Olkin, I. and Sobel, M., 1977. Selecting and ordering populations: a new statistical methodology. New York, Wiley.Google Scholar
- Hedges, L. V. and Olkin, I., 1985. Statistical methods for meta-analysis. New York, Academic Press.Google Scholar
- Jiao, Y., Jia, P., Wang, X., Su, N., Yu, S., Zhang, D., Ma, L., Feng, Q., Jin, Z., Li, L., Xue, Y., Cheng, Z., Zhao, H., Han, B. and Deng, X. W., 2005. A tiling microarray expression analysis of rice chromosome 4 suggests a chromosome-level regulation of transcription. The Plant Cell 17:1641-15-657.PubMedCrossRefGoogle Scholar
- Li, W., Meyer, C. A. and Liu, X. S., 2006. A hidden Markov model for analyzing ChIP-chip experiments on genome tiling arrays and its application to p53 binding sequences. Bioinformatics 21(Suppl.1):i274–i282.Google Scholar
- Lippman, Z., Gendrel, A-V., Black, M., Vaughn, M. W., Dedhia, N., McCombie, W. R., Lavine, K., Mittal, V., May, B., Kasschau, K. D., Carrington, J. C., Doerge, R. W., Colot, V. and Martienssen, R., 2004. Role of transposable elements in heterochromatin and epigenetic control. Nature 430:471–476.PubMedCrossRefGoogle Scholar
- Vaughn, M., Tanurdzic, M., Lippman, Z., Jiang, H., Carrasquillo, R., Colot, V., Doerge, R.W., and Martienssen, R.A. 2007. Epigenetic natural variation in Arabidopsis thaliana. Public Library of Science (PLoS) Biology. 5(7): e174.Google Scholar
- Yoo, S-Y. 2008. A two-stage statistical approach for integrating epigenomic results with gene expression data using tiling array technology. Ph.D. Dissertation. Purdue University. West Lafayette, IN, USA.Google Scholar
- Zhang, X., Yazaki, J., Sundaresan, A., Cokus, S., Chan, S. W.-L., Chen, H., Henderson, I. R., Shinn, P., Pellegrini, M., Jacobsen, S. E., and Ecker, J. R., 2006 Genome-wide high-resolution mapping and functional analysis of DNA methylation in Arabidopsis. Cell 126:1189–1201.PubMedCrossRefGoogle Scholar