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Handbook of Statistical Bioinformatics pp 31–53Cite as

Statistical and Computational Studies on Alternative Splicing

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Abstract

The accumulating genome sequences and other high-throughput data have shed light on the extent and importance of alternative splicing in functional regulation. Alternative splicing dramatically increases the transcriptome and proteome diversity of higher organisms by producing multiple splice variants from different combinations of exons. It has an important role in many biological processes including nervous system development and programmed cell death. Many human diseases including cancer arise from defects in alternative splicing and its regulation. This chapter reviews statistical and computational methods on genome-wide alternative splicing studies.

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References

  1. Wang, E. T., Sandberg, R., Luo, S., Khrebtukova, I., Zhang, L., Mayr, C., Kingsmore, S. F., Schroth, G. P., & Burge, C. B. (2008). Alternative isoform regulation in human tissue transcriptomes. Nature, 456, 470–476.

    Article  Google Scholar 

  2. Pan, Q., Shai, O., Lee, L. J., Frey, B. J., & Blencowe, B. J. (2008). Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing. Nature Genetics, 40, 1413–1415.

    Article  Google Scholar 

  3. Gilbert, W. (1978). Why genes in pieces? Nature, 271, 501.

    Article  Google Scholar 

  4. Breitbart, R. E., Andreadis, A., & Nadal-Ginard, B. (1987). Alternative splicing: A ubiquitous mechanism for the generation of multiple protein isoforms from single genes. Annual Review of Biochemistry, 56, 467–495.

    Article  Google Scholar 

  5. Johnson, J. M., Castle, J., Garrett-Engele, P., Kan, Z., Loerch, P. M., Armour, C. D., Santos, R., Schadt, E. E., Stoughton, R., & Shoemaker, D. D. (2003). Genome-wide survey of human alternative pre-mRNA splicing with exon junction microarrays. Science, 302, 2141–2144.

    Article  Google Scholar 

  6. Kan, Z., Rouchka, E. C., Gish, W. R., & States, D. J. (2001). Gene structure prediction and alternative splicing analysis using genomically aligned ESTs. Genome Research, 11, 889–900.

    Article  Google Scholar 

  7. Mironov, A. A., Fickett, J. W., & Gelfand, M. S. (1999). Frequent alternative splicing of human genes. Genome Research, 9, 1288–1293.

    Article  Google Scholar 

  8. Modrek, B., Resch, A., Grasso, C., & Lee, C. (2001). Genome-wide detection of alternative splicing in expressed sequences of human genes. Nucleic Acids Research, 29, 2850–2859.

    Article  Google Scholar 

  9. Graveley, B. R., Kaur, A., Gunning, D., Zipursky, S. L., Rowen, L., & Clemens, J. C. (2004). The organization and evolution of the dipteran and hymenopteran Down syndrome cell adhesion molecule (Dscam) genes. RNA, 10, 1499–1506.

    Article  Google Scholar 

  10. Missler, M., & Sudhof, T. C. (1998). Neurexins: Three genes and 1001 products. Trends in Genetics, 14, 20–26.

    Article  Google Scholar 

  11. Zdobnov, E. M., von Mering, C., Letunic, I., Torrents, D., Suyama, M., Copley, R. R., Christophides, G. K., Thomasova, D., Holt, R. A., Subramanian, G. M., Mueller, H. M., Dimopoulos, G., Law, J. H., Wells, M. A., Birney, E., Charlab, R., Halpern, A. L., Kokoza, E., Kraft, C. L., Lai, Z., Lewis, S., Louis, C., Barillas-Mury, C., Nusskern, D., Rubin, G. M., Salzberg, S. L., Sutton, G. G., Topalis, P., Wides, R., Wincker, P., Yandell, M., Collins, F. H., Ribeiro, J., Gelbart, W. M., Kafatos, F. C., & Bork, P. (2002). Comparative genome and proteome analysis of Anopheles gambiae and Drosophila melanogaster. Science, 298, 149–159.

    Article  Google Scholar 

  12. Kent, W. J. (2002). BLAT – the BLAST-like alignment tool. Genome Research, 12, 656–664.

    MathSciNet  Google Scholar 

  13. Florea, L., Hartzell, G., Zhang, Z., Rubin, G. M., & Miller, W. (1998). A computer program for aligning a cDNA sequence with a genomic DNA sequence. Genome Research, 8, 967–974.

    Google Scholar 

  14. Wu, T. D., & Watanabe, C. K. (2005). GMAP: A genomic mapping and alignment program for mRNA and EST sequences. Bioinformatics, 21, 1859–1875.

    Article  Google Scholar 

  15. van Nimwegen, E., Paul, N., Sheridan, R., & Zavolan, M. (2006). SPA: A probabilistic algorithm for spliced alignment. PLoS Genetics, 2, e24.

    Article  Google Scholar 

  16. Florea, L., Di Francesco, V., Miller, J., Turner, R., Yao, A., Harris, M., Walenz, B., Mobarry, C., Merkulov, G. V., Charlab, R., Dew, I., Deng, Z., Istrail, S., Li, P., & Sutton, G. (2005). Gene and alternative splicing annotation with AIR. Genome Research, 15, 54–66.

    Article  Google Scholar 

  17. Heber, S., Alekseyev, M., Sze, S. H., Tang, H., & Pevzner, P. A. (2002). Splicing graphs and EST assembly problem. Bioinformatics, 18(Suppl 1), S181–S188.

    Article  Google Scholar 

  18. Kim, N., Shin, S., & Lee, S. (2005). ECgene: Genome-based EST clustering and gene modeling for alternative splicing. Genome Research, 15, 566–576.

    Article  Google Scholar 

  19. Xing, Y., Yu, T., Wu, Y. N., Roy, M., Kim, J., & Lee, C. (2006). An expectation-maximization algorithm for probabilistic reconstructions of full-length isoforms from splice graphs. Nucleic Acids Research, 34, 3150–3160.

    Article  Google Scholar 

  20. Leparc, G. G., & Mitra, R. D. (2007). Non-EST-based prediction of novel alternatively spliced cassette exons with cell signaling function in Caenorhabditis elegans and human. Nucleic Acids Research, 35, 3192–3202.

    Article  Google Scholar 

  21. Sorek, R., & Ast, G. (2003). Intronic sequences flanking alternatively spliced exons are conserved between human and mouse. Genome Research, 13, 1631–1637.

    Article  Google Scholar 

  22. Sorek, R., Shemesh, R., Cohen, Y., Basechess, O., Ast, G., & Shamir, R. (2004). A non-EST-based method for exon-skipping prediction. Genome Research, 14, 1617–1623.

    Article  Google Scholar 

  23. Yeo, G. W., Van Nostrand, E., Holste, D., Poggio, T., & Burge, C. B. (2005). Identification and analysis of alternative splicing events conserved in human and mouse. Proceedings of the National Academy of Sciences of the United States of America, 102, 2850–2855.

    Article  Google Scholar 

  24. Chen, L., & Zheng, S. (2008). Identify alternative splicing events based on position-specific evolutionary conservation. PLoS One, 3, e2806.

    Article  Google Scholar 

  25. Breiman, L. (2001). Random forests. Machine Learning, 45, 5–32.

    Article  MATH  Google Scholar 

  26. Parmley, J. L., Urrutia, A. O., Potrzebowski, L., Kaessmann, H., & Hurst, L. D. (2007). Splicing and the evolution of proteins in mammals. PLoS Biology, 5, e14.

    Article  Google Scholar 

  27. Fairbrother, W. G., Holste, D., Burge, C. B., & Sharp, P. A. (2004). Single nucleotide polymorphism-based validation of exonic splicing enhancers. PLoS Biology, 2, e268.

    Article  Google Scholar 

  28. Boutz, P. L., Stoilov, P., Li, Q., Lin, C. H., Chawla, G., Ostrow, K., Shiue, L., Ares, M., Jr., & Black, D. L. (2007). A post-transcriptional regulatory switch in polypyrimidine tract-binding proteins reprograms alternative splicing in developing neurons. Genes & Development, 21, 1636–1652.

    Article  Google Scholar 

  29. Clark, T. A., Schweitzer, A. C., Chen, T. X., Staples, M. K., Lu, G., Wang, H., Williams, A., & Blume, J. E. (2007). Discovery of tissue-specific exons using comprehensive human exon microarrays. Genome Biology, 8, R64.

    Article  Google Scholar 

  30. Yeo, G. W., Xu, X., Liang, T. Y., Muotri, A. R., Carson, C. T., Coufal, N. G., & Gage, F. H. (2007). Alternative splicing events identified in human embryonic stem cells and neural progenitors. PLoS Computational Biology, 3, 1951–1967.

    Article  Google Scholar 

  31. Castle, J. C., Zhang, C., Shah, J. K., Kulkarni, A. V., Kalsotra, A., Cooper, T. A., & Johnson, J. M. (2008). Expression of 24,426 human alternative splicing events and predicted cis regulation in 48 tissues and cell lines. Nature Genetics, 40, 1416–1425.

    Article  Google Scholar 

  32. Clark, T. A., Sugnet, C. W., & Ares, M., Jr. (2002). Genomewide analysis of mRNA processing in yeast using splicing-specific microarrays. Science, 296, 907–910.

    Article  Google Scholar 

  33. Cline, M. S., Blume, J., Cawley, S., Clark, T. A., Hu, J. S., Lu, G., Salomonis, N., Wang, H., & Williams, A. (2005). ANOSVA: A statistical method for detecting splice variation from expression data. Bioinformatics, 21(Suppl. 1), i107–i115.

    Article  Google Scholar 

  34. Purdom, E., Simpson, K. M., Robinson, M. D., Conboy, J. G., Lapuk, A. V., & Speed, T. P. (2008). FIRMA: A method for detection of alternative splicing from exon array data. Bioinformatics, 24, 1707–1714.

    Article  Google Scholar 

  35. Wang, H., Hubbell, E., Hu, J. S., Mei, G., Cline, M., Lu, G., Clark, T., Siani-Rose, M. A., Ares, M., Kulp, D. C., & Haussler, D. (2003). Gene structure-based splice variant deconvolution using a microarray platform. Bioinformatics, 19(Suppl. 1), i315–i322.

    Article  Google Scholar 

  36. Li, C., & Wong, W. H. (2001). Model-based analysis of oligonucleotide arrays: Expression index computation and outlier detection. Proceedings of the National Academy of Sciences of the United States of America, 98, 31–36.

    Article  MATH  Google Scholar 

  37. Anton, M. A., Gorostiaga, D., Guruceaga, E., Segura, V., Carmona-Saez, P., Pascual-Montano, A., Pio, R., Montuenga, L. M., & Rubio, A. (2008). SPACE: An algorithm to predict and quantify alternatively spliced isoforms using microarrays. Genome Biology, 9, R46.

    Article  Google Scholar 

  38. Shai, O., Morris, Q. D., Blencowe, B. J., & Frey, B. J. (2006). Inferring global levels of alternative splicing isoforms using a generative model of microarray data. Bioinformatics, 22, 606–613.

    Article  Google Scholar 

  39. Pan, Q., Shai, O., Misquitta, C., Zhang, W., Saltzman, A. L., Mohammad, N., Babak, T., Siu, H., Hughes, T. R., Morris, Q. D., Frey, B. J., & Blencowe, B. J. (2004). Revealing global regulatory features of mammalian alternative splicing using a quantitative microarray platform. Molecular Cell, 16, 929–941.

    Article  Google Scholar 

  40. Fagnani, M., Barash, Y., Ip, J. Y., Misquitta, C., Pan, Q., Saltzman, A. L., Shai, O., Lee, L., Rozenhek, A., Mohammad, N., Willaime-Morawek, S., Babak, T., Zhang, W., Hughes, T. R., van der Kooy, D., Frey, B. J., & Blencowe, B. J. (2007). Functional coordination of alternative splicing in the mammalian central nervous system. Genome Biology, 8, R108.

    Article  Google Scholar 

  41. Nagalakshmi, U., Wang, Z., Waern, K., Shou, C., Raha, D., Gerstein, M., & Snyder, M. (2008). The transcriptional landscape of the yeast genome defined by RNA sequencing. Science, 320, 1344–1349.

    Article  Google Scholar 

  42. Wilhelm, B. T., Marguerat, S., Watt, S., Schubert, F., Wood, V., Goodhead, I., Penkett, C. J., Rogers, J., & Bahler, J. (2008). Dynamic repertoire of a eukaryotic transcriptome surveyed at single-nucleotide resolution. Nature, 453, 1239–1243.

    Article  Google Scholar 

  43. Lister, R., O’Malley, R. C., Tonti-Filippini, J., Gregory, B. D., Berry, C. C., Millar, A. H., & Ecker, J. R. (2008). Highly integrated single-base resolution maps of the epigenome in Arabidopsis. Cell, 133, 523–536.

    Article  Google Scholar 

  44. Cloonan, N., Forrest, A. R., Kolle, G., Gardiner, B. B., Faulkner, G. J., Brown, M. K., Taylor, D. F., Steptoe, A. L., Wani, S., Bethel, G., Robertson, A. J., Perkins, A. C., Bruce, S. J., Lee, C. C., Ranade, S. S., Peckham, H. E., Manning, J. M., McKernan, K. J., & Grimmond, S. M. (2008). Stem cell transcriptome profiling via massive-scale mRNA sequencing. Nature Methods, 5, 613–619.

    Article  Google Scholar 

  45. Mortazavi, A., Williams, B. A., McCue, K., Schaeffer, L., & Wold, B. (2008). Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nature Methods, 5, 621–628.

    Article  Google Scholar 

  46. Marioni, J. C., Mason, C. E., Mane, S. M., Stephens, M., & Gilad, Y. (2008). RNA-seq: An assessment of technical reproducibility and comparison with gene expression arrays. Genome Research, 18, 1509–1517.

    Article  Google Scholar 

  47. Sultan, M., Schulz, M. H., Richard, H., Magen, A., Klingenhoff, A., Scherf, M., Seifert, M., Borodina, T., Soldatov, A., Parkhomchuk, D., Schmidt, D., O’Keeffe, S., Haas, S., Vingron, M., Lehrach, H., & Yaspo, M. L. (2008). A global view of gene activity and alternative splicing by deep sequencing of the human transcriptome. Science, 321, 956–960.

    Article  Google Scholar 

  48. Jiang, H., & Wong, W. H. (2009). Statistical inferences for isoform expression in RNA-Seq. Bioinformatics,25, 1026–1032.

    Google Scholar 

  49. Zheng, S., & Chen, L. (2009). A hierarchical Bayesian model for comparing transcriptomes at the individual transcript isoform level. Nucleic Acids Research, 37,e75.

    Article  Google Scholar 

  50. Stamm, S., Riethoven, J. J., Le Texier, V., Gopalakrishnan, C., Kumanduri, V., Tang, Y., Barbosa-Morais, N. L., & Thanaraj, T. A. (2006). ASD: A bioinformatics resource on alternative splicing. Nucleic Acids Research, 34, D46–D55.

    Article  Google Scholar 

  51. Zhou, Z., Licklider, L. J., Gygi, S. P., & Reed, R. (2002). Comprehensive proteomic analysis of the human spliceosome. Nature, 419, 182–185.

    Article  Google Scholar 

  52. Jurica, M. S., & Moore, M. J. (2003). Pre-mRNA splicing: Awash in a sea of proteins. Molecular Cell, 12, 5–14.

    Article  Google Scholar 

  53. Wang, Z., & Burge, C. B. (2008). Splicing regulation: From a parts list of regulatory elements to an integrated splicing code. RNA, 14, 802–813.

    Article  Google Scholar 

  54. Huh, G. S., & Hynes, R. O. (1994). Regulation of alternative pre-mRNA splicing by a novel repeated hexanucleotide element. Genes & Development, 8, 1561–1574.

    Article  Google Scholar 

  55. McCullough, A. J., & Berget, S. M. (1997). G triplets located throughout a class of small vertebrate introns enforce intron borders and regulate splice site selection. Molecular Cell Biology, 17, 4562–4571.

    Google Scholar 

  56. Chou, M. Y., Underwood, J. G., Nikolic, J., Luu, M. H., & Black, D. L. (2000). Multisite RNA binding and release of polypyrimidine tract binding protein during the regulation of c-src neural-specific splicing. Molecular Cell, 5, 949–957.

    Article  Google Scholar 

  57. Wang, Z., Rolish, M. E., Yeo, G., Tung, V., Mawson, M., & Burge, C. B. (2004). Systematic identification and analysis of exonic splicing silencers. Cell, 119, 831–845.

    Article  Google Scholar 

  58. Zhang, X. H., & Chasin, L. A. (2004). Computational definition of sequence motifs governing constitutive exon splicing. Genes & Development, 18, 1241–1250.

    Article  Google Scholar 

  59. Black, D. L. (2003). Mechanisms of alternative pre-messenger RNA splicing. Annual Review of Biochemistry, 72, 291–336.

    Article  Google Scholar 

  60. Matlin, A. J., Clark, F., & Smith, C. W. (2005). Understanding alternative splicing: Towards a cellular code. Nature Review. Molecular Cell Biology, 6, 386–398.

    Article  Google Scholar 

  61. Fu, X. D. (2004). Towards a splicing code. Cell, 119, 736–738.

    Article  Google Scholar 

  62. Chen, L., & Zheng, S. (2009). Studying alternative splicing regulatory networks through partial correlation analysis. Genome Biology, 10, R3.

    Article  Google Scholar 

  63. Efron, B. (2007). Correlation and large-scale simultaneous significance testing. Journal of the American Statistical Association, 102, 93–103.

    Article  MathSciNet  MATH  Google Scholar 

  64. Faustino, N. A., & Cooper, T. A. (2003). Pre-mRNA splicing and human disease. Genes & Development, 17, 419–437.

    Article  Google Scholar 

  65. Garcia-Blanco, M. A., Baraniak, A. P., & Lasda, E. L. (2004). Alternative splicing in disease and therapy. Nature Biotechnology, 22, 535–546.

    Article  Google Scholar 

  66. Blencowe, B. J. (2000). Exonic splicing enhancers: Mechanism of action, diversity and role in human genetic diseases. Trends in Biochemical Sciences, 25, 106–110.

    Article  Google Scholar 

  67. Krawczak, M., Thomas, N. S., Hundrieser, B., Mort, M., Wittig, M., Hampe, J., & Cooper, D. N. (2007). Single base-pair substitutions in exon-intron junctions of human genes: Nature, distribution, and consequences for mRNA splicing. Human Mutation, 28, 150–158.

    Article  Google Scholar 

  68. Blencowe, B. J. (2006). Alternative splicing: New insights from global analyses. Cell, 126, 37–47.

    Article  Google Scholar 

  69. Li, H. R., Wang-Rodriguez, J., Nair, T. M., Yeakley, J. M., Kwon, Y. S., Bibikova, M., Zheng, C., Zhou, L., Zhang, K., Downs, T., Fu, X. D., & Fan, J. B. (2006). Two-dimensional transcriptome profiling: Identification of messenger RNA isoform signatures in prostate cancer from archived paraffin-embedded cancer specimens. Cancer Research, 66, 4079–4088.

    Article  Google Scholar 

  70. Li, C., Kato, M., Shiue, L., Shively, J. E., Ares, M., Jr., & Lin, R. J. Cell type and culture condition-dependent alternative splicing in human breast cancer cells revealed by splicing-sensitive microarrays. Cancer Research, 66, 1990–1999 (2006).

    Article  Google Scholar 

  71. Relogio, A., Ben-Dov, C., Baum, M., Ruggiu, M., Gemund, C., Benes, V., Darnell, R. B., & Valcarcel, J. (2005). Alternative splicing microarrays reveal functional expression of neuron-specific regulators in Hodgkin lymphoma cells. The Journal of Biological Chemistry, 280, 4779–4784.

    Article  Google Scholar 

  72. Kwan, T., Benovoy, D., Dias, C., Gurd, S., Serre, D., Zuzan, H., Clark, T. A., Schweitzer, A., Staples, M. K., Wang, H., Blume, J. E., Hudson, T. J., Sladek, R., & Majewski, J. (2007). Heritability of alternative splicing in the human genome. Genome Research, 17, 1210–1218.

    Article  Google Scholar 

  73. Huang, Y. H., Chen, Y. T., Lai, J. J., Yang, S. T., & Yang, U. C. (2002). PALS db: Putative Alternative Splicing database. Nucleic Acids Research, 30, 186–190.

    Article  Google Scholar 

  74. Huang, H. D., Horng, J. T., Lin, F. M., Chang, Y. C., & Huang, C. C. (2005). SpliceInfo: An information repository for mRNA alternative splicing in human genome. Nucleic Acids Research, 33, D80–D85.

    Article  Google Scholar 

  75. Kim, N., Shin, S., & Lee, S. (2004). ASmodeler: Gene modeling of alternative splicing from genomic alignment of mRNA, EST and protein sequences. Nucleic Acids Research, 32,W181–W186.

    Article  Google Scholar 

  76. Kim, P., Kim, N., Lee, Y., Kim, B., Shin, Y., & Lee, S. (2005). ECgene: Genome annotation for alternative splicing. Nucleic Acids Research, 33, D75–D79.

    Article  Google Scholar 

  77. Leipzig, J., Pevzner, P., & Heber, S. (2004). The Alternative Splicing Gallery (ASG): Bridging the gap between genome and transcriptome. Nucleic Acids Research, 32, 3977–3983.

    Article  Google Scholar 

  78. Lee, B. T., Tan, T. W., & Ranganathan, S. (2004). DEDB: A database of Drosophila melanogaster exons in splicing graph form. BMC Bioinformatics, 5, 189.

    Article  Google Scholar 

  79. Bhasi, A., Pandey, R. V., Utharasamy, S. P., & Senapathy, P. (2007). EuSplice: A unified resource for the analysis of splice signals and alternative splicing in eukaryotic genes. Bioinformatics, 23, 1815–1823.

    Article  Google Scholar 

  80. Castrignano, T., D’Antonio, M., Anselmo, A., Carrabino, D., D’Onorio De Meo, A., D’Erchia, A. M., Licciulli, F., Mangiulli, M., Mignone, F., Pavesi, G., Picardi, E., Riva, A., Rizzi, R., Bonizzoni, P., & Pesole, G. (2008). ASPicDB: A database resource for alternative splicing analysis. Bioinformatics, 24, 1300–1304.

    Article  Google Scholar 

  81. Holste, D., Huo, G., Tung, V., & Burge, C. B. (2006). HOLLYWOOD: A comparative relational database of alternative splicing. Nucleic Acids Research, 34, D56–D62.

    Article  Google Scholar 

  82. Shionyu, M., Yamaguchi, A., Shinoda, K., Takahashi, K., & Go, M. (2009). AS-ALPS: A database for analyzing the effects of alternative splicing on protein structure, interaction and network in human and mouse. Nucleic Acids Research, 37, D305–D309.

    Article  Google Scholar 

  83. Ryan, M. C., Zeeberg, B. R., Caplen, N. J., Cleland, J. A., Kahn, A. B., Liu, H., & Weinstein, J. N. (2008). SpliceCenter: A suite of web-based bioinformatic applications for evaluating the impact of alternative splicing on RT-PCR, RNAi, microarray, and peptide-based studies. BMC Bioinformatics, 9, 313.

    Article  Google Scholar 

  84. Floris, M., Orsini, M., & Thanaraj, T. A. (2008). Splice-mediated Variants of Proteins (SpliVaP) – data and characterization of changes in signatures among protein isoforms due to alternative splicing. BMC Genomics, 9, 453.

    Article  Google Scholar 

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  1. Molecular and Computational Biology, Department of Biological Sciences, University of Southern California, 1050 Childs Way, Los Angeles, California, 90089, USA

    Liang Chen

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  1. Liang Chen
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Correspondence to Liang Chen .

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  1. , Institute of Statistics, National Chiao Tung University, Ta Hsueh Road 1001, Hsinchu, 30050, Taiwan, Taiwan R.O.C.

    Henry Horng-Shing Lu

  2. , Department of Empirical Inference, MPI for Intelligent Systems, Spemannstraße 38, Tübingen, 72076, Germany

    Bernhard Schölkopf

  3. School of Medicine, Dept. Epidemiology & Public Health, Yale University, College Street 60, New Haven, 06520, Connecticut, USA

    Hongyu Zhao

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Chen, L. (2011). Statistical and Computational Studies on Alternative Splicing. In: Lu, HS., Schölkopf, B., Zhao, H. (eds) Handbook of Statistical Bioinformatics. Springer Handbooks of Computational Statistics. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-16345-6_2

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