| 研究生: |
張琬琦 Chang, Wan-Chi |
|---|---|
| 論文名稱: |
藉由變異數倒數加權法進行 cDNA 微陣列影像中基因表現比值之穩健估計量 A Robust Ratio Estimator of Gene Expression via Inverse-Variance Weighting for cDNA Microarray Images |
| 指導教授: |
詹世煌
Chan, Shih-Huang |
| 學位類別: |
博士 Doctor |
| 系所名稱: |
管理學院 - 統計學系 Department of Statistics |
| 論文出版年: | 2008 |
| 畢業學年度: | 96 |
| 語文別: | 英文 |
| 論文頁數: | 73 |
| 中文關鍵詞: | 點品質(Spot quality) 、變異數倒數加權法(Inverse-variance weighting) 、微陣列影像(Microarray image) 、型態分割(Segmentation) |
| 外文關鍵詞: | Microarray image, Inverse-variance weighting, Segmentation, Spot quality |
| 相關次數: | 點閱:79 下載:1 |
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本文主要是對 cDNA 微陣列影像,提供一個基因表現比值的穩健估計方法,稱為META。目前文獻在微陣列影像處理上,在經過格線劃分後,多數著重在基因點影像位元素之型態分割, 藉以得到前景光與背景光的強度值估計,再推算基因表現值。但在型態分割的過程中,往往因為雜訊干擾造成分割不完全,以致所估算的前景光訊息比背景光微弱,所得到的基因表現值亦因而不可靠。本論文嘗試不經過既定的前、背景光型態分割過程,而是以各個位元素上 (pixel-by-pixel) 的基因表現值,藉由同心圓區域分組方式,依各區變異給予相對應之權數,再估算出整個點之基因表現值。透過七種點影像模式設定下,分別進行2000次模擬。 META在多數情況下,都能有令人滿意的表現比值估計。進一步經過實例分析,不論有無雜訊干擾,META 所得到的基因表現值,比已知的方法(如 k-means 分割法、GTMM,或是紅綠光迴歸係數斜率值法) 所得到的 MSE 都還要小。本文另提出點品質指標 (spot quality metric),以進一步確認較佳的基因表現估計值進入後端分析,提供 cDNA 微陣列更可靠的結果。
In microarray processing, the appearance of artifacts, donuts, and irregularly shaped spots is a problem. In current microarray analysis, most approaches stress the segmentation of pixel intensities rather than emphasizing ratio estimators. To avoid segmenting spot target areas and to minimize sensitivity to aberrant pixels, we propose a robust ratio estimator of gene expression via inverse-variance weighting. Moreover, a metric is proposed to evaluate the spot quality. Image simulations present that most of setting artifact spots can be estimated satisfactorily by META.
Results from numerical examples explored reveal that the proposed algorithm is superior to existing approaches with respect to mean square error. The acceptance quality measure recommended confirms the validity of the proposed ratio estimator.
Adams, R. and Bischof, L., 1994. Seeded region growing. IEEE Trans. Pattern Anal. Machine Intell. 16, 641-647.
Axon Instruments Inc., 2005. GenePix Pro 6.0, User’s Guide, Axon Instruments Inc. (http://www.axon.com)
Baek, J., Son, Y. S., and McLachlan. G. J., 2007. Segmentation and intensity estimation of microarray images using a gamma-t mixture model. Bioinformatics 23, 458-465.
Becker, W. and Kennedy, P., 1992. A lesson in least squares and R squared. Am Stat. 46, 282-283.
Blekas, K., Galatsanos, N. P., Likas, A., and Lagaris, I. E., 2005. Mixture Model Analysis of DNA Microarrya Images. IEEE Tran. Med. Imaging 24, 901-919.
Brown, C. S., Goodwin, P. C., and Sorger, P. K., 2001. Image metrics in the statistical analysis of DNA microarray data. Proc. Natl. Acad. Sci. USA 98, 8944- 8949.
Bozinov, D. and Rahnenfűhrer, J., 2002. Unsupervised technique for robust target separation and analysis of DNA microarray spots through adaptive pixel clustering. Bioinformatics 18, 747-756.
Brändle, N., Bischof, H., Lapp, H., 2003. Robust DNA microarray image analysis. Machine Vision and Applications 15, 11-28.
Buhler, J., Ideker, T., Haynor, D., 2000. Dapper: Improved Techniques for Finding Spots on DNA Microarrays. UW CSE Technical Report UWTR.
Chen, Y., Kamat, V., Dougherty, E. R., Bittner M. L., Meltzer P. S. and Trent J. M., 2002. Ratio statistics of gene expression levels and applications to microarray data analysis. Bioinformatics 18, 1207-1215.
Demirkaya, O., Asyali, M. H., and Shoukri, M. M., 2005. Segmentation of cDNA microarray spots using Markov random filed modeling. Bioinformatics 21, 2994-3000.
Ekstrøm, C. T., Bak, S., Kristensen, C., and Rudemo, M., 2004. Spot shape modeling and data transformations for microarrays. Bioinformatics 20, 2270-2278.
Ekstrøm, C. T., Bak, S., Kristensen, C., and Rudemo, M., 2005. Pixel-level signal modeling with spatial correlation for two-colour microarrays. Stat. Appl. in Genet. Mol. Biol. 4, Article6.
Eisen, M. B., 1999. http://rana.stanford.edu/software/ for software and documentation.
Glasbey, C. A., and Ghazal. P., 2003. Combinatorial image analysis of DNA microarray features. Bioinformatics 19, 194-203.
Gottardo, R., Besag, J., Stephens, M. and Murua, A., 2006. Probabilistic segmentation and intensity estimation for microarray images. Biostatistics 7, 85-99.
GSI Lumonics, 1999. QuantArray Analysis Software, Operator’s Manual.
Kosinski, C., Li, V. S., Chan, A. S. Zhang, J., Ho, C., Tsui, W. Y., Chan, T. L., Mifflin, R.C. , Powell, D. W., Yuen, S. T., Leung, S. Y., and Chen, X. 2007. Gene expression patterns of human colon tops and basal crypts and BMP antagonists as intestinal stem cell niche factors. Proc Natl Acad Sci U S A. 104, 15418-23.
Kvålseth, T., 1985. Cautionary note about R2. Am Stat., 39, 279-285.
Kim, J. H., Kim, H. Y., and Lee, Y. S., 2001. A novel method using edge detection for signal extraction from cDNA microarray image analysis. Exp. Mol. Med., 33: 83-88.
Li, Q., Fraley, C., Bumgarner, R. E., Yeung, K. Y., and Raftery A. E., 2005. Donuts, scratches and blanks: robust model-based segmentation of microarray images. Bioinformatics 21, 2875-2882.
Lukac, R., Plataniotis, K. N., Smolka, B., and Venetsanopoulos, A. N., 2004. A multichannel order-statistic technique for cDNA microarray image processing. IEEE Trans. Nanobioscience 3, 272-285.
Moran, P. A. P., 1950. Notes on continuous stochastic phenomena. Biometrika 37, 17-23.
Nagarajan, R. and Peterson, C. A., 2002. Identifying spots in microarray images. IEEE Trans. Nanobioscience 1, 78-84.
Novikov, E. and Barillot, E., 2005a. A robust algorithm for ratio estimation in two-color microarray experiments. J Bioinform Comput Biol. 3, 1411-1428.
Novikov, E. and Barillot, E., 2005b. An algorithm for automatic evaluation of the spot quality in two-color DNA microarray experiments. BMC Bioinformatics 6(293).
Rahnenfűhrer, J. and Bozinov, D., 2004. Hybrid clustering for microarray image analysis combining intensity and shape features. BMC Bioinformatics 5(47).
Sauer, U. and Preininger, C. and Hany-Schmatzberger, R. 2005. Quick and simple: quality control of microarray data. Bioinformatics 21, 1572-1578.
Schena, M., Shalon, D., Davis, R. W., Brown, P. O. 1995. Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 270, 467-470.
Steinfath, M., Wruch, W., Seidel, H., Lehrach, H., Radelof, U., and O’Brien, J., 2001. Automated image analysis for array hybridization experiments. Bioinformatics 17, 634-641.
Tran, P. H., Peiffer D. A., Shin, Y., Meek, L. M., Brody, J. P., and Cho, K. W. Y., 2002. Microarray optimizations: increasing spot accuracy and automation identification of true microarray signals. Nucleic Acids Research 30, e54.
Tseng, G. C., Oh, M. K., Rohlin, L., Liao, J. C. and Wong, W. H., 2001. Issues in cDNA microarray analysis: quality filtering, channel normalization, models of variations and assessment of gene effects. Nucleic Acids Research 29, 2549-2557.
Wang, X., Ghosh, S. and Guo S. W., 2001. Quantitative quality control in microarray image processing and data acquisition. Nucleic Acids Res. 29(e75).
Wang, X., Hessner, M. J. Wu, Y. Pati, N. and Ghosh S., 2003. Quantitative quality control in microarray experiments and the application in data filtering, normalization and false positive rate prediction. Bioinformatics 19, 1341-1347.
Wierling, C. K., Steinfath, M., Elge, T., Schulze-Kremer, D., Aanstad, P., Clark, M., Lehrach, H., and Herwig, R., 2002. Simulation of DNA array hybridization experiments and evaluation of critical parameters during subsequent image and data analysis. BMC Bioinformatics 3(29).
Yang, Y. H., Buckley, M.J., and Speed T.P., 2001. Analysis of cDNA microarray images. Briefings in Bioinformatics, 2, 341-349.