Abstract
During the last decade, analytical methods for the detection and quantification of proteins and peptides in biological samples have been considerably improved. It is therefore now possible to compare simultaneously the expression levels of hundreds or thousands of proteins in different types of tissue, for example, normal and cancerous, or in different cell lines. In this chapter, we illustrate statistical designs for such proteomics experiments as well as methods for the analysis of resulting data. In particular, we focus on the preprocessing and analysis of protein expression levels recorded by the use of either two-dimensional gel electrophoresis or mass spectrometry.
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References
Nesvizhskii, A. I., Keller, A., Kolker, E., and Aebersold, R. (2002) A statistical model for identifying proteins by tandem mass spectrometry. Anal Chem 75, 4646–4658.
Urfer, W., Grzegorczyk, M., and Jung, K. (2006) Statistics for proteomics: a review of tools for analyzing experimental data. Pract Proteomics 1, 48–55.
Klose, J., and Kobalz, U. (1995) Two-dimensional electrophoresis of proteins: and updated protocol and implications for functional analysis of the genome. Electrophoresis 4, 1034–1059.
Ünlü, M., Morgan, M. E., and Minden, J. S. (1997) Difference gel electrophoresis: A single gel method for detecting changes in protein extracts. Electrophoresis 18, 2071–2077.
Aebersold, R., and Goodlett, D. R. (2001) Mass spectrometry in proteomics. Chem Rev 101, 269–295.
Stühler, K., Pfeiffer, K., Joppich, C., Stephan, C., Jung, K., Müller, M., Schmidt, O., van Hall, A., Hamacher, M., Urfer, W., Meyer, H. E., and Marcus, K. (2006) Pilot study of the Human Proteome Organisation Brain Proteome Project: Applying different 2-DE techniques to monitor proteomic changes during murine brain development. Proteomics 6, 4899–4913.
Karp, N. A., McCormick, P. S., Russell, M. R., and Lilley, K. S. (2007) Experimental and statistical considerations to avoid false conclusions in proteomic studies using differential in-gel electrophoresis. Mol Cell Proteomics 6, 1354–1364.
Fodor, I. K., Nelson, D. O., Alegria-Hartman, M., Robbins, K., Langlois, R. G., Turteltaub, K. W., Corzett, T.H., and McCutchen-Maloney, S.L. (2005) Statistical challenges in analysis of two-dimensional difference gel electrophoresis experiments using DeCyder. Bioinformatics 21, 3733–3740.
Chich, J.-F., David, O., Villers, F., Schaeffer, B., Lutomski, D., and Huet, S. (2007) Statistics for proteomics: Experimental design and 2-DE differential analysis. J Chromatogr B 849, 261–272.
Kreil, D. P., Karp, N. A., and Lilley, K. S. (2004) DNA microarray normalization methods can remove bias from differential protein expression analysis of 2D difference gel electrophoresis results. Bioinformatics 20, 2026–3740.
Huber, W., Heydebreck, A., von Sültmann, H., Poustka, A., and Vingron, M. (2002) Variance stabilization applied to microarray data calibration and the quantification of differential expression. Bioinformatics 18, S96–S104.
Bolstad, B. M., Irizarry R. A., Astrand, M., and Speed, T. P. (2003) A comparison of normalization methods for high density oligonucleotide array data based on bias and variance. Bioinformatics 19, 185–193.
Jung, K., Gannoun, A., Sitek, B., Meyer, H. E., Stühler, K., and Urfer, W. (2005) Analysis of dynamic protein expression data. RevStat-Stat J 3, 99–111.
Jung, K., Gannoun, A., Sitek, B., Apostolov, O., Schramm, A., Meyer, H. E., Stühler, K., and Urfer, W. (2006) Statistical evaluation of methods for the analysis of dynamic protein expression data from a tumor study. RevStat-Stat J 4, 67–80.
Smyth, G. K. (2004) Linear models and empirical Bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol 3, Article 3.
Dudoit, S., Shaffer, J. P., and Boldrick, J. C. (2003) Multiple hypothesis testing in microarray experiments. Stat Sci 18, 71–103.
Jung, K., Poschmann, G., Podwojski, K., Eisenacher, M., Kohl, M., Pfeiffer, K., Meyer, H. E., Stühler, K., and Stephan, C. (2009) adjusted confidence intervals for the expression change of proteins observed in 2-dimensional difference gel electrophoresis. J Proteomics Bioinform 2, 78–87.
Gygi, S. P., Rist, B., Gerber, S. A., Turecek, F., Gelb, M. H., and Aebersold, R. (1999) Quantitative analysis of complex protein mixtures using isotope-coded affinity tags. Nat Biotechnol 17, 994–999.
Ross, P. L., Huang, Y. N., Marchese, J. N., et al. (2004) Multiplexed protein quantitation in Saccharomyces cerevisiae using aminereactive isobaric tagging reagents. Mol Cell Proteomics 3, 1154–1169.
Boehm, A. M., Pütz, S., Altenhöfer, D., Sickmann, A., and Falk, M. (2007) Precise protein quantification based on peptide quantification using iTRAQ™. BMC Bioinformatics 8, 214.
Jeffries, N. (2005) Algorithms for alignment of mass spectrometry proteomic data. Bioinformatics 21, 3066–3073.
Pusch, W., Flocco, M. T., Leung, S.-M., Thiele, H., and Kostrzewa, M. (2003) Mass spectrometry-based clinical proteomics. Pharmacogenomics 4, 463–476.
Jeffries, N. O. (2004) Performance of a genetic algorithm for mass spectrometry proteomics. BMC Bioinformatics 5, 180.
Lilien, R. H., Farid, H., and Donald, B. R. (2003) Probabilistic disease classification of expression dependent proteomic data from mass spectrometry of human serum. J Comput Biol 10, 925–946.
Zhang, X., Lu, X., Shi, Q., Xu, X., Leung, H., Harris, L. N., Iglehart, J. D., Miron, A., Liu, J. S., and Wong, W. H. (2006) Recursive SVM feature selection and sample classification for mass-spectrometry and microarray data. BMC Bioinformatics 7, 197.
Cairns, D. A., Barrett, J. H., Billingham, L. J., Stanley, A. J., Xinarianos, G., Field, J. K., Johnson, P. J., Selby, P. J., and Banks, R. E. (2009) Sample size determination in clinical proteomic profiling experiments using mass spectrometry for class comparison. Proteomics 9, 74–86.
Fu, W. J., Dougherty, E. R., Mallick, B., and Carrol, R. (2005) How many samples are needed to build a classifier: A general sequential approach. Bioinformatics 21, 63–70.
Sitek, B., Apostolov, O., K. S., Pfeiffer, K., Meyer, H. E., Eggert, A., and Schramm, A. (2005) Identification of dynamic proteome changes upon ligand activation of trk-receptors using two-dimensional fluorescence difference gel electrophoresis and mass spectrometry. Mol Cell Proteomics 4, 291–299.
Brunner, E., Domhof, S., and Langer, F. (2002) Nonparametric Analysis of Longitudinal Data in Factorial Experiments. John Wiley & Sons, New York.
Grzegorczyk, M. (2007) Extracting protein regulatory networks with graphical models. Proteomics 7(S1), 51–59.
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Jung, K. (2010). Statistical Methods for Proteomics. In: Bang, H., Zhou, X., van Epps, H., Mazumdar, M. (eds) Statistical Methods in Molecular Biology. Methods in Molecular Biology, vol 620. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-580-4_18
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DOI: https://doi.org/10.1007/978-1-60761-580-4_18
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