Abstract
Glycosylphosphatidylinositol (GPI) lipid modification is an important protein posttranslational modification found in many organisms, and GPI-anchoring is confined to the C-terminus of the target protein. We have developed a novel computational protocol for identifying GPI-anchored proteins, which is more accurate than previously proposed protocols. It uses an optimized support vector machine (SVM) classifier to recognize the C-terminal sequence pattern and uses a voting system based on SignalP version 3.0 to determine the presence or absence of the N-terminal signal of a typical GPI-anchored protein. The SVM classifier shows an accuracy of 96%, and the area under the receiver operating characteristic (ROC) curve is 0.97 under a 5-fold cross-validation test. Fourteen of 15 proteins in our sensitivity test dataset and 19 of the 20 proteins experimentally identified by Hamada et al. that were not included in the training dataset were identified correctly. This suggests that our protocol is considerably effective on unseen data. A proteome-wide survey applying the protocol to S. cerevisiae identified 88 proteins as putative GPI-anchored proteins.
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References
Powell, S.K., Cunningham, B.A., Edelman, G.M., Rodriguez-Boulan, E.: Targeting of transmembrane and GPI-anchored forms of N-CAM to opposite domains of a polarized epithelial cell. Nature 353, 76–77 (1991)
Ikezawa, H., Yamanegi, M., Taguchi, R., Miyashita, T., Ohyabu, T.: Studies on phosphatidylinositol phosphodiesterase (phospholipase C type) of Bacillus cereus. I. purification, properties and phosphatase-releasing activity. Biochim. Biophys. Acta. 450, 154–164 (1976)
Rijnboutt, S., Jansen, G., Posthuma, G., Hynes, J.B., Schornagel, J.H., Strous, G.J.: Endocytosis of GPI-linked membrane folate receptor-alpha. J. Cell Biol. 132, 35–47 (1996)
Stahl, N., Baldwin, M.A., Hecker, R., Pan, K.M., Burlingame, A.L., Prusiner, S.B.: Glycosylinositol phospholipid anchors of the scrapie and cellular prion proteins contain sialic acid. Biochemistry 31, 5043–5053 (1992)
Cashman, N.R., Loertscher, R., Nalbantoglu, J., Shaw, I., Kascsak, R.J., Bolton, D.C., Bendheim, P.E.: Cellular isoform of the scrapie agent protein participates in lymphocyte activation. Cell 61, 185–192 (1990)
Udenfriend, S., Kodukula, K.: Prediction of omega site in nascent precursor of glycosylphosphatidylinositol protein. Methods Enzymol. 250, 571–582 (1995)
Udenfriend, S., Kodukula, K.: How glycosylphosphatidylinositol-anchored membrane proteins are made. Annu. Rev. Biochem. 64, 563–591 (1995)
Caro, L.H., Tettelin, H., Vossen, J.H., Ram, A.F., van den Ende, H., Klis, F.M.: In silicio identification of glycosyl-phosphatidylinositol-anchored plasma-membrane and cell wall proteins of Saccharomyces cerevisiae. Yeast 13, 1477–1489 (1997)
von Heijne, G.: A new method for predicting signal sequence cleavage sites. Nucleic Acids Res. 14, 4683–4690 (1986)
Nuoffer, C., Horvath, A., Riezman, H.: Analysis of the sequence requirements for glycosylphosphatidylinositol anchoring of Saccharomyces cerevisiae Gas1 protein. J. Biol. Chem. 268, 10558–10563 (1993)
De Groot, P.W., Hellingwerf, K.J., Klis, F.M.: Genome-wide identification of fungal GPI proteins. Yeast 20, 781–796 (2003)
Nielsen, H., Engelbrecht, J., Brunak, S., von Heijne, G.: Identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites. Protein Eng. 10, 1–6 (1997)
Nakai, K., Kanehisa, M.: A knowledge base for predicting protein localization sites in eukaryotic cells. Genomics 14, 897–911 (1992)
Eisenhaber, B., Schneider, G., Wildpaner, M., Eisenhaber, F.: A sensitive predictor for potential GPI lipid modification sites in fungal protein sequences and its application to genome-wide studies for Aspergillus nidulans, Candida albicans, Neurospora crassa, Saccharomyces cerevisiae and Schizosaccharomyces pombe. J. Mol. Biol. 337, 243–253 (2004)
Fankhauser, N., Maser, P.: Identification of GPI anchor attachment signals by a Kohonen self-organizing map. Bioinformatics 21, 1846–1852 (2005)
Caras, I.W., Weddell, G.N.: Signal Peptide for Protein Secretion Directing Glycophospholipid Membrane Anchor Attachment. Science 243, 1196–1198 (1989)
Eisenhaber, B., Bork, P., Eisenhaber, F.: Prediction of potential GPI-modification sites in proprotein sequences. J. Mol. Biol. 292, 741–758 (1999)
Vapnik, V.N.: The Nature of Statistical Learning Theory. Springer, New York (1995)
Vapnik, V.N.: Statistical Learning Theory. John Wiley & Sons, Inc., Chichester (1998)
Zien, A., Ratsch, G., Mika, S., Scholkopf, B., Lengauer, T., Muller, K.R.: Engineering support vector machine kernels that recognize translation initiation sites. Bioinformatics 16, 799–807 (2000)
Ding, C.H., Dubchak, I.: Multi-class protein fold recognition using support vector machines and neural networks. Bioinformatics 17, 349–358 (2001)
Hua, S.J., Sun, Z.R.: Support vector machine approach for protein subcellular localization prediction. Bioinformatics 17, 721–728 (2001)
Chang, C.C., Lin, C.J.: LIBSVM: a library for support vector machines. Software (2001), http://www.csie.ntu.edu.tw/~cjlin/libsvm
Kyte, J., Doolittle, R.F.: A Simple Method for Displaying the Hydropathic Character of a Protein. J. Mol. Biol. 157, 105–132 (1982)
Shi, Y., Eberhart, R.C.: A modified particle swarm optimizer. In: Proceedings of the IEEE Congress on Evolutionary Computation (CEC 1998), Piscataway, NJ, pp. 69–73 (1998)
Bendtsen, J.D., Nielsen, H., von Heijne, G., Brunak, S.: Improved prediction of signal peptides: SignalP 3.0. J. Mol. Biol. 340, 783–795 (2004)
Menne, K.M., Hermjakob, H., Apweiler, R.: A comparison of signal sequence prediction methods using a test set of signal peptides. Bioinformatics 16, 741–742 (2000)
Hamada, K., Terashima, H., Arisawa, M., Yabuki, N., Kitada, K.: Amino acid residues in the omega-minus region participate in cellular localization of yeast glycosylphosphatidylinositol-attached proteins. J. Bacteriol. 181, 3886–3889 (1999)
Caras, I.W., Weddell, G.N., Williams, S.R.: Analysis of the Signal for Attachment of a Glycophospholipid Membrane Anchor. J. Cell Biol. 108, 1387–1396 (1989)
Moran, P., Caras, I.W.: A nonfunctional sequence converted to a signal for glycophosphatidylinositol membrane anchor attachment. J. Cell Biol. 115, 329–336 (1991)
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Cao, W., Sumikoshi, K., Terada, T., Nakamura, S., Kitamoto, K., Shimizu, K. (2009). Computational Protocol for Screening GPI-anchored Proteins. In: Rajasekaran, S. (eds) Bioinformatics and Computational Biology. BICoB 2009. Lecture Notes in Computer Science(), vol 5462. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-00727-9_17
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DOI: https://doi.org/10.1007/978-3-642-00727-9_17
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