Skip to main content

Finding long protein products of alternatively spliced genes

Background

In eukaryotes, pre-mRNA molecules undergo splicing, which is the removal of sequences called introns to produce mature mRNA transcripts whose open reading frames (ORFs) may then be translated to proteins. Often this splicing step may be performed in many ways - a situation known as alternative splicing [1, 2] that can be described by structures such as splice graphs [3]. Alternative splicings, even those that differ only slightly, may result in proteins with substantially different biological properties [4, 5].

Materials and methods

We have developed an algorithm for finding the longest ORFs of alternatively spliced transcripts described by splice graphs. Our algorithm executes in time linear in the size of the splice graph (and therefore optimal), determining the splicings that result in an open reading frame encoding a maximal-length protein for that gene. We show how our algorithm may be used to help identify biologically interesting protein products from RNA-seq data.

References

  1. Sammeth M, Foissac S, Guigó R: A general definition and nomenclature for alternative splicing events. PLoS Computational Biology 2008., 4(8):

    Google Scholar 

  2. Sugnet CW, Kent WJ, Ares M, Haussler D: Transcriptome and genome conservation of alternative splicing events in humans and mice. In Pacific Symposium on Biocomputing Edited by: Altman RB, Dunker AK, Hunter L, Jung TA, Klein TE, World Scientific. 2004, 66–77.

    Google Scholar 

  3. Heber S, Alekseyev M, Sze SH, Tang H, Pevzner PA: Splicing graphs and EST assembly problem. Bioinformatics 2002, 18(suppl 1):S181-S188. 10.1093/bioinformatics/18.suppl_1.S181

    Article  PubMed  Google Scholar 

  4. Harrow J, Nagy A, Reymond A, Alioto T, Patthy L, Antonarakis S, Guigo R: Identifying protein-coding genes in genomic sequences. Genome Biology 2009, 10: 201. 10.1186/gb-2009-10-1-201

    Article  PubMed Central  PubMed  Google Scholar 

  5. Xing Y, Yu T, Wu YN, Roy M, Kim J, Lee C: An expectation-maximization algorithm for probabilistic reconstructions of full-length isoforms from splice graphs. Nucleic Acids Research 2006, 34(10):3150–3160. 10.1093/nar/gkl396

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Moore N, Jaromczyk JW: Finding a longest open reading frame of an alternatively spliced gene. Proc. IEEE Intl Conf. on Bioinformatics and Biomedicine 2011 (BIBM 2011) Workshops, Workshop on Integrative Data Analysis in Systems Biology (IDASB) 2011, 215–222.

    Chapter  Google Scholar 

Download references

Acknowledgements

This work was partially supported by NIGMS Grant 1R01GM086888-01, Kentucky NSF-EPSCoR Grant 0814194, NSF Grant EF-0523661, and USDA-NRA Grant 2005-35319-16141.

An earlier version of this work [6] was presented at presented at the Workshop on Integrative Data Analysis in Systems Biology in 2011.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jerzy W Jaromczyk.

Rights and permissions

Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and permissions

About this article

Cite this article

Moore, N., Jaromczyk, J.W. & Schardl, C.L. Finding long protein products of alternatively spliced genes. BMC Bioinformatics 13 (Suppl 12), A12 (2012). https://doi.org/10.1186/1471-2105-13-S12-A12

Download citation

  • Published:

  • DOI: https://doi.org/10.1186/1471-2105-13-S12-A12

Keywords