Abstract
In recent years, genome-wide detection of alternative splicing based on Expressed Sequence Tag (EST) sequence alignments with mRNA and genomic sequences has dramatically expanded our understanding of the role of alternative splicing in functional regulation. This chapter reviews the data, methodology, and technical challenges of these genome-wide analyses of alternative splicing, and briefly surveys some of the uses to which such alternative splicing databases have been put. For example, with proper alternative splicing database schema design, it is possible to query genome-wide for alternative splicing patterns that are specific to particular tissues, disease states (e.g., cancer), gender, or developmental stages. EST alignments can be used to estimate exon inclusion or exclusion level of alternatively spliced exons and evolutionary changes for various species can be inferred from exon inclusion level. Such databases can also help automate design of probes for RT-PCR and microarrays, enabling high throughput experimental measurement of alternative splicing.
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References
Gilbert, W. (1978) Nature 271, 501.
Black, D. L. (2003) Annu Rev Biochem 72, 291–336.
Black, D. L., Grabowski, P. J. (2003) Prog Mol Subcell Biol 31, 187–216.
Brett, D., Pospisil, H., Valcarcel, J., et al. (2002) Nat Genet 30, 29–30.
Burke, J., Wang, H., Hide, W., et al. (1998) Genome Res 8, 276–290.
Croft, L., Schandorff, S., Clark, F., et al. (2000) Nat Genet 24, 340–341.
Grabowski, P. J., Black, D. L. (2001) Prog Neurobiol 65, 289–308.
8.Graveley, B. R. (2001) Trends Genet 17, 100–107.
Gupta, S., Zink, D., Korn, B., et al. (2004) Bioinformatics 20, 2579–2585.
Huang, H. D., Horng, J. T., Lee, C. C., et al. (2003) Genome Biol 4, R29.
Huang, Y. H., Chen, Y. T., Lai, J. J., et al. (2002) Nucleic Acids Res 30, 186–190.
Kan, Z., Rouchka, E. C., Gish, W. R., et al. (2001) Genome Res 11, 889–900.
Kim, N., Shin, S., Lee, S. (2004) Nucleic Acids Res 32, W181–186.
Kim, N., Shin, S., Lee, S. (2005) Genome Res 15, 566–576.
Kim, P., Kim, N., Lee, Y., et al. (2005) Nucleic Acids Res 33, D75–79.
Kochiwa, H., Suzuki, R., Washio, T., et al. (2002) Genome Res 12, 1286–1293.
Lee, C., Atanelov, L., Modrek, B., et al. (2003) Nucleic Acids Res 31, 101–105.
Lee, C., Wang, Q. (2005) Brief Bioinform 6, 23–33.
Maniatis, T., Tasic, B. (2002) Nature 418, 236–243.
Mironov, A. A., Fickett, J. W., Gelfand, M. S. (1999) Genome Res 9, 1288–1293.
Modrek, B., Lee, C. J. (2003) Nat Genet 34, 177–180.
Modrek, B., Resch, A., Grasso, C., et al. (2001) Nucleic Acids Res 29, 2850–2859.
Thanaraj, T. A., Stamm, S., Clark, F., et al. (2004) Nucleic Acids Res 32 Database issue, D64–69.
Wang, B. B., Brendel, V. (2006) Proc Natl Acad Sci U S A 103, 7175–7180.
Caceres, J. F., Kornblihtt, A. R. (2002) Trends Genet 18, 186–193.
Levanon, E. Y., Sorek, R. (2003) TARGETS 2, 109–114.
Li, C., Kato, M., Shiue, L., et al. (2006) Cancer Res 66, 1990–1999.
Bailey, L. C., Jr., Searls, D. B., Overton, G. C. (1998) Genome Res 8, 362–376.
Boue, S., Vingron, M., Kriventseva, E., et al. (2002) Bioinformatics 18 Suppl 2, S65–S73.
Gelfand, M. S., Dubchak, I., Dralyuk, I., et al. (1999) Nucleic Acids Res 27, 301–302.
Gopalan, V., Tan, T. W., Lee, B. T., et al. (2004) Nucleic Acids Res 32 Database issue, D59–63.
Heber, S., Alekseyev, M., Sze, S. H., et al. (2002) Bioinformatics 18 Suppl 1, S181–188.
Kan, Z., States, D., Gish, W. (2002) Genome Res 12, 1837–1845.
Kawamoto, S., Yoshii, J., Mizuno, K., et al. (2000) Genome Res 10, 1817–1827.
Krause, A., Haas, S. A., Coward, E., et al. (2002) Nucleic Acids Res 30, 299–300.
Pospisil, H., Herrmann, A., Bortfeldt, R. H., et al. (2004) Nucleic Acids Res 32 Database issue, D70–74.
Xie, H., Zhu, W. Y., Wasserman, A., et al. (2002) Genomics 80, 326–330.
Xu, Q., Modrek, B., Lee, C. (2002) Nucleic Acids Res 30, 3754–3766.
Yeo, G., Holste, D., Kreiman, G., et al. (2004) Genome Biol 5, R74.
Zavolan, M., Kondo, S., Schonbach, C., et al. (2003) Genome Res 13, 1290–300.
Zavolan, M., van Nimwegen, E., Gaaster-land, T. (2002) Genome Res 12, 1377–1385.
Nagasaki, H., Arita, M., Nishizawa, T., et al. (2006) Bioinformatics 22, 1211–1216.
Kent, W. J. (2002) Genome Res 12, 656–664.
Wu, T. D., Watanabe, C. K. (2005) Bioin-formatics 21, 1859–1875.
Boguski, M. S., Lowe, T. M., Tolstoshev, C. M. (1993) Nat Genet 4, 332–333.
Maglott, D. R., Katz, K. S., Sicotte, H., et al. (2000) Nucleic Acids Res 28, 126–128.
Pruitt, K. D., Katz, K. S., Sicotte, H., et al. (2000) Trends Genet 16, 44–47.
Pruitt, K. D., Maglott, D. R. (2001) Nucleic Acids Res 29, 137–140.
Pruitt, K. D., Tatusova, T., Maglott, D. R. (2005) Nucleic Acids Res 33, D501–504.
Pruitt, K. D., Tatusova, T., Maglott, D. R. (2003) Nucleic Acids Res 31, 34–37.
Burge, C., Karlin, S. (1997) J Mol Biol 268, 78–94.
Korf, I., Flicek, P., Duan, D., et al. (2001) Bioinformatics 17 Suppl 1, S140–148.
Salamov, A. A., Solovyev, V. V. (2000) Genome Res 10, 516–522.
Yeh, R. F., Lim, L. P., Burge, C. B. (2001) Genome Res 11, 803–816.
Shomer, B. (1997) Comput Appl Biosci 13, 545–547.
Kersey, P., Hermjakob, H., Apweiler, R. (2000) Bioinformatics 16, 1048–1049.
Boguski, M. S., Schuler, G. D. (1995) Nat Genet 10, 369–371.
Burke, J., Davison, D., Hide, W. (1999) Genome Res 9, 1135–1142.
Cariaso, M., Folta, P., Wagner, M., et al. (1999) Bioinformatics 15, 965–973.
Christoffels, A., van Gelder, A., Greyling, G., et al. (2001) Nucleic Acids Res 29, 234–238.
Liang, F., Holt, I., Pertea, G., et al. (2000) Nat Genet 25, 239–240.
Liang, F., Holt, I., Pertea, G., et al. (2000) Nucleic Acids Res 28, 3657–3665.
Miller, R. T., Christoffels, A. G., Gopalakrishnan, C., et al. (1999) Genome Res 9, 1143–1155.
Pertea, G., Huang, X., Liang, F., et al. (2003) Bioinformatics 19, 651–652.
Quackenbush, J., Cho, J., Lee, D., et al. (2001) Nucleic Acids Res 29, 159–164.
Quackenbush, J., Liang, F., Holt, I., et al. (2000) Nucleic Acids Res 28, 141–145.
Schuler, G. D. (1997) J Mol Med 75, 694–698.
Schuler, G. D., Boguski, M. S., Stewart, E. A., et al. (1996) Science 274, 540–546.
Bono, H., Kasukawa, T., Furuno, M., et al. (2002) Nucleic Acids Res 30, 116–118.
Carter, M. G., Piao, Y., Dudekula, D. B., et al. (2003) C R Biol 326, 931–940.
Gerhard, D. S., Wagner, L., Feingold, E. A., et al. (2004) Genome Res 14, 2121–2127.
Hayashizaki, Y. (2003) C R Biol 326, 923–929.
Lamesch, P., Milstein, S., Hao, T., et al. (2004) Genome Res 14, 2064–2069.
Sasaki, D., Kawai, J. (2004) Tanpakushitsu Kakusan Koso 49, 2627–2634.
Benson, D. A., Karsch-Mizrachi, I., Lipman, D. J., et al. (2000) Nucleic Acids Res 28, 15–18.
Benson, D. A., Karsch-Mizrachi, I., Lipman, D. J., et al. (2002) Nucleic Acids Res 30, 17–20.
Benson, D. A., Karsch-Mizrachi, I., Lipman, D. J., et al. (2003) Nucleic Acids Res 31, 23–27.
Benson, D. A., Karsch-Mizrachi, I., Lipman, D. J., et al. (2006) Nucleic Acids Res 34, D16–20.
Benson, D. A., Karsch-Mizrachi, I., Lipman, D. J., et al. (2004) Nucleic Acids Res 32 Database issue, D23–26.
Burks, C., Fickett, J. W., Goad, W. B., et al. (1985) Comput Appl Biosci 1, 225–233.
Arnold, J., Hilton, N. (2003) Nature 422, 821–822.
Carroll, S. B. (2003) Nature 422, 849–857.
Collins, F. S., Green, E. D., Guttmacher, A. E., et al. (2003) Nature 422, 835–847.
Collins, F. S., Morgan, M., Patrinos, A. (2003) Science 300, 286–290.
Frazier, M. E., Johnson, G. M., Thomassen, D. G., et al. (2003) Science 300, 290–293.
Bernal, A., Ear, U., Kyrpides, N. (2001) Nucleic Acids Res 29, 126–127.
Kyrpides, N. C. (1999) Bioinformatics 15, 773–774.
Liolios, K., Tavernarakis, N., Hugenholtz, P., et al. (2006) Nucleic Acids Res 34, D332–334.
Jenuth, J. P. (2000) Methods Mol Biol 132, 301–312.
Hinrichs, A. S., Karolchik, D., Baertsch, R., et al. (2006) Nucleic Acids Res 34, D590–598.
Karolchik, D., Baertsch, R., Diekhans, M., et al. (2003) Nucleic Acids Res 31, 51–54.
Kent, W. J., Sugnet, C. W., Furey, T. S., et al. (2002) Genome Res 12, 996–1006.
Birney, E. (2003) Cold Spring Harb Symp Quant Biol 68, 213–215.
Birney, E., Andrews, D., Bevan, P., et al. (2004) Nucleic Acids Res 32, D468–470.
Birney, E., Andrews, D., Caccamo, M., et al. (2006) Nucleic Acids Res 34, D556–561.
Birney, E., Andrews, T. D., Bevan, P., et al. (2004) Genome Res 14, 925–928.
Butler, D. (2000) Nature 406, 333.
Clamp, M., Andrews, D., Barker, D., J., et al. (2003) Nucleic Acids Res 31, 38–42.
Hammond, M. P., Birney, E. (2004) Trends Genet 20, 268–272.
Hubbard, T., Andrews, D., Caccamo, M., et al. (2005) Nucleic Acids Res 33, D447–453.
Hubbard, T., Barker, D., Birney, E., et al. (2002) Nucleic Acids Res 30, 38–41.
Blanchette, M., Kent, W. J., Riemer, C., et al. (2004) Genome Res 14, 708–715.
Altschul, S. F., Gish, W., Miller, W., et al. (1990) J Mol Biol 215, 403–410.
Altschul, S. F., Madden, T. L., Schaffer, A. A., et al. (1997) Nucleic Acids Res 25, 3389–3402.
Gish, W., States, D. J. (1993) Nat Genet 3, 266–272.
Madden, T. L., Tatusov, R. L., Zhang, J. (1996) Methods Enzymol 266, 131–141.
Zhang, J., Madden, T. L. (1997) Genome Res 7, 649–656.
Zhang, Z., Schwartz, S., Wagner, L., et al. (2000) J Comput Biol 7, 203–214.
van Nimwegen, E., Paul, N., Sheridan, A., et al. (2006) PLoS Genetics 2, 587–605.
Florea, L., Hartzell, G., Zhang, Z., et al. (1998) Genome Res 8, 967–974.
Bedell, J. A., Korf, I., Gish, W. (2000) Bioinformatics 16, 1040–1041.
Lee, W. H., Vega, V. B. (2004) Bioinfor-matics 20, 2863–2864.
Lopez, R., Silventoinen, V., Robinson, S., et al. (2003) Nucleic Acids Res 31, 3795–3798.
Jurka, J. (2000) Trends Genet 16, 418–420.
Jurka, J., Kapitonov, V. V., Pavlicek, A., et al. (2005) Cytogenet Genome Res 110, 462–467.
Aiyar, A. (2000) Methods Mol Biol 132, 221–241.
Thompson, J. D., Higgins, D. G., Gibson, T. J. (1994) Nucleic Acids Res 22, 4673–4680.
Olson, S. A. (2002) Brief Bioinform 3, 87–91.
Rice, P., Longden, I., Bleasby, A. (2000) Trends Genet 16, 276–277.
Hamelryck, T., Manderick, B. (2003) Bioinformatics 19, 2308–2310.
Mangalam, H. (2002) Brief Bioinform 3, 296–302.
Grasso, C., Lee, C. (2004) Bioinformatics 20, 1546–1556.
Grasso, C., Modrek, B., Xing, Y., et al. (2004) Pac Symp Biocomput 29–41.
Grasso, C., Quist, M., Ke, K., et al. (2003) Bioinformatics 19, 1446–1448.
Lee, C. (2003) Bioinfor matics 19, 999–1008.
Lee, C., Grasso, C., Sharlow, M. F. (2002) Bioinformatics 18, 452–464.
Xing, Y., Resch, A., Lee, C. (2004) Genome Res 14, 426–441.
Hollenberg, N. K. (2002) Curr Hypertens Rep 4, 267.
Wilson, F. H., Disse-Nicodeme, S., Cho-ate, K. A., et al. (2001) Science 293, 1107–1112.
Huang, X., Li, J., Lu, L., et al. (2005) J Androl 26, 189–196.
Le, K., Mitsouras, K., Roy, M., et al. (2004) Nucleic Acids Res 32, e180.
Pan, Q., Saltzman, A. L., Kim, Y. K., et al. (2006) Genes Dev 20, 153–158.
Pan, Q., Shai, O., Misquitta, C., et al. (2004) Mol Cell 16, 929–941.
Shai, O., Morris, Q. D., Blencowe, B. J., et al. (2006) Bioinformatics 22, 606–613.
Wang, H., Hubbell, E., Hu, J. S., et al. (2003) Bioinformatics 19 Suppl 1, i315–322.
Zheng, C. L., Kwon, Y. S., Li, H. R., et al. (2005) Rna 11, 1767–1776.
Kim, N., Lim, D., Lee, S., et al. (2005) Nucleic Acids Res 33, W681–685.
Rozen, S., Skaletsky, H. (2000) Methods Mol Biol 132, 365–386.
Karolchik, D., Hinrichs, A. S., Furey, T. S., et al. (2004) Nucleic Acids Res 32 Database issue, D493–496.
Sorek, R., Safer, H. M. (2003) Nucleic Acids Res 31, 1067–1074.
Edwalds-Gilbert, G., Veraldi, K. L., Mil-carek, C. (1997) Nucleic Acids Res 25, 2547–2561.
Gautheret, D., Poirot, O., Lopez, F., et al. (1998) Genome Res 8, 524–530.
Pauws, E., van Kampen, A. H., van de Graaf, S. A., et al. (2001) Nucleic Acids Res 29, 1690–1694.
Legendre, M., Gautheret, D. (2003) BMC Genomics 4, 7.
Mignone, F., Grillo, G., Licciulli, F., et al. (2005) Nucleic Acids Res 33, D141–146.
Pesole, G., Liuni, S., Grillo, G., et al. (1999) Nucleic Acids Res 27, 188–191.
Pesole, G., Liuni, S., Grillo, G., et al. (2000) Nucleic Acids Res 28, 193–196.
Pesole, G., Liuni, S., Grillo, G., et al. (2002) Nucleic Acids Res 30, 335–340.
Pesole, G., Liuni, S., Grillo, G., et al. (1998) Nucleic Acids Res 26, 192–195.
Beaudoing, E., Freier, S., Wyatt, J. R., et al. (2000) Genome Res 10, 1001–1010.
Beaudoing, E., Gautheret, D. (2001) Genome Res 11, 1520–1526.
Ner-Gaon, H., Halachmi, R., Savaldi-Goldstein, S., et al. (2004) Plant J 39, 877–885.
Galante, P. A., Sakabe, N. J., Kirschbaum-Slager, N., et al. (2004) Rna 10, 757–765.
Hiller, M., Huse, K., Platzer, M., et al. (2005) Nucleic Acids Res 33, 5611–5621.
Michael, I. P., Kurlender, L., Memari, N., et al. (2005) Clin Chem 51, 506–515.
Mauro, M. J., Druker, B. J. (2001) Curr Oncol Rep 3, 223–227.
Mauro, M. J., Druker, B. J. (2001) Oncologist 6, 233–238.
Mauro, M. J., O'Dwyer, M., Heinrich, M. C., et al. (2002) J Clin Oncol 20, 325–334.
Mauro, M. J., O'Dwyer, M. E., Druker, B. J. (2001) Cancer Chemother Pharmacol 48 Suppl 1, S77–78.
Rowley, J. D. (2001) Nat Rev Cancer 1, 245–250.
Finta, C., Warner, S. C., Zaphiropou-los, P. G. (2002) Histol Histopathol 17, 677–682.
Finta, C., Zaphiropoulos, P. G. (2002) J Biol Chem 277, 5882–5890.
Flouriot, G., Brand, H., Seraphin, B., et al. (2002) J Biol Chem 277, 26244–26251.
Communi, D., Suarez-Huerta, N., Dus-sossoy, D., et al. (2001) J Biol Chem 276, 16561–16566.
Magrangeas, F., Pitiot, G., Dubois, S., et al. (1998) J Biol Chem 273, 16005–16010.
Roux, M., Leveziel, H., Amarger, V. (2006) BMC Genomics 7, 71.
Dandekar, T., Sibbald, P. R. (1990) Nucleic Acids Res 18, 4719–4725.
Kim, N., Kim, P., Nam, S., et al. (2006) Nucleic Acids Res 34, D21–24.
Kim, N., Shin, S., Cho, K.-H., et al. (2004) Genomics & Informatics 2, 61–66.
Romani, A., Guerra, E., Trerotola, M., et al. (2003) Nucleic Acids Res 31, e17.
Shao, X., Shepelev, V., Fedorov, A. (2006) Bioinformatics 22, 692–698.
Modrek, B., Lee, C. (2002) Nat Genet 30, 13–19.
Acknowledgments
This work was funded by a Dreyfus Foundation Teacher-Scholar Award to C.J.L., and by the National Institutes of Health through the NIH Roadmap for Medical Research, Grant U54 RR021813 entitled Center for Computational Biology (CCB). Information on the National Centers for Biomedical Computing can be obtained from http://nihroadmap.nih.gov/bioinformatics.
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Kim, N., Lee, C. (2008). Bioinformatics Detection of Alternative Splicing. In: Keith, J.M. (eds) Bioinformatics. Methods in Molecular Biology™, vol 452. Humana Press. https://doi.org/10.1007/978-1-60327-159-2_9
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