Abstract
In this paper we present a novel expectation-maximization algorithm for inference of alternative splicing isoform frequencies from high-throughput transcriptome sequencing (RNA-Seq) data. Our algorithm exploits disambiguation information provided by the distribution of insert sizes generated during sequencing library preparation, and takes advantage of base quality scores, strand and read pairing information if available. Empirical experiments on synthetic datasets show that the algorithm significantly outperforms existing methods of isoform and gene expression level estimation from RNA-Seq data. The Java implementation of IsoEM is available at http://dna.engr.uconn.edu/software/IsoEM/.
Work supported in part by NSF awards IIS-0546457, IIS-0916401, and IIS-0916948.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Anton, M., Gorostiaga, D., Guruceaga, E., Segura, V., Carmona-Saez, P., Pascual-Montano, A., Pio, R., Montuenga, L., Rubio, A.: SPACE: an algorithm to predict and quantify alternatively spliced isoforms using microarrays. Genome Biology 9(2), R46 (2008)
Birol, I., Jackman, S.D., Nielsen, C.B., Qian, J.Q., Varhol, R., Stazyk, G., Morin, R.D., Zhao, Y., Hirst, M., Schein, J.E., Horsman, D.E., Connors, J.M., Gascoyne, R.D., Marra, M.A., Jones, S.J.M.: De novo transcriptome assembly with ABySS. Bioinformatics 25(21), 2872–2877 (2009)
Carninci, P., et al.: The Transcriptional Landscape of the Mammalian Genome. Science 309(5740), 1559–1563 (2005)
Feng, J., Li, W., Jiang, T.: Inference of isoforms from short sequence reads. In: Berger, B. (ed.) RECOMB 2010. LNCS, vol. 6044, pp. 138–157. Springer, Heidelberg (2010)
Hansen, K.D., Brenner, S.E., Dudoit, S.: Biases in Illumina transcriptome sequencing caused by random hexamer priming. Nucl. Acids Res. p. gkq224 (2010) (advance access)
Hiller, D., Jiang, H., Xu, W., Wong, W.H.: Identifiability of isoform deconvolution from junction arrays and RNA-Seq. Bioinformatics 25(23), 3056–3059 (2009)
Jackson, B., Schnable, P., Aluru, S.: Parallel short sequence assembly of transcriptomes. BMC Bioinformatics 10(suppl. 1), S14+ (2009)
Jiang, H., Wong, W.H.: Statistical inferences for isoform expression in RNA-Seq. Bioinformatics 25(8), 1026–1032 (2009)
Lacroix, V., Sammeth, M., Guigo, R., Bergeron, A.: Exact transcriptome reconstruction from short sequence reads. In: Crandall, K.A., Lagergren, J. (eds.) WABI 2008. LNCS (LNBI), vol. 5251, pp. 50–63. Springer, Heidelberg (2008)
Langmead, B., Trapnell, C., Pop, M., Salzberg, S.: Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biology 10(3), R25 (2009)
Li, B., Ruotti, V., Stewart, R.M., Thomson, J.A., Dewey, C.N.: RNA-Seq gene expression estimation with read mapping uncertainty. Bioinformatics 26(4), 493–500 (2010)
Mortazavi, A., Williams, B.A.A., McCue, K., Schaeffer, L., Wold, B.: Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nature methods (2008)
Paşaniuc, B., Zaitlen, N., Halperin, E.: Accurate estimation of expression levels of homologous genes in RNA-seq experiments. In: Berger, B. (ed.) RECOMB 2010. LNCS, vol. 6044, pp. 397–409. Springer, Heidelberg (2010)
Richard, H., Schulz, M.H., Sultan, M., Nurnberger, A., Schrinner, S., Balzereit, D., Dagand, E., Rasche, A., Lehrach, H., Vingron, M., Haas, S.A., Yaspo, M.-L.: Prediction of alternative isoforms from exon expression levels in RNA-Seq experiments. Nucl. Acids Res. 38(10), e112+ (2010)
She, Y., Hubbell, E., Wang, H.: Resolving deconvolution ambiguity in gene alternative splicing. BMC Bioinformatics 10(1), 237 (2009)
Temple, G., et al.: The completion of the Mammalian Gene Collection (MGC). Genome Research 19(12), 2324–2333 (2009)
Trapnell, C., Pachter, L., Salzberg, S.L.: TopHat: discovering splice junctions with RNA-Seq. Bioinformatics 25(9), 1105–1111 (2009)
Trapnell, C., Williams, B.A., Pertea, G., Mortazavi, A., Kwan, G., van Baren, M.J., Salzberg, S.L., Wold, B.J., Pachter, L.: Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nature biotechnology 28(5), 511–515 (2010)
Wang, E.T., Sandberg, R., Luo, S., Khrebtukova, I., Zhang, L., Mayr, C., Kingsmore, S.F., Schroth, G.P., Burge, C.B.: Alternative isoform regulation in human tissue transcriptomes. Nature 456(7221), 470–476 (2008)
Wang, Z., Gerstein, M., Snyder, M.: RNA-Seq: a revolutionary tool for transcriptomics. Nat. Rev. Genet. 10(1), 57–63 (2009)
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Nicolae, M., Mangul, S., Măndoiu, I., Zelikovsky, A. (2010). Estimation of Alternative Splicing isoform Frequencies from RNA-Seq Data. In: Moulton, V., Singh, M. (eds) Algorithms in Bioinformatics. WABI 2010. Lecture Notes in Computer Science(), vol 6293. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-15294-8_17
Download citation
DOI: https://doi.org/10.1007/978-3-642-15294-8_17
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-15293-1
Online ISBN: 978-3-642-15294-8
eBook Packages: Computer ScienceComputer Science (R0)