A Polynomial Delay Algorithm for the Enumeration of Bubbles with Length Constraints in Directed Graphs and Its Application to the Detection of Alternative Splicing in RNA-seq Data

  • Gustavo Sacomoto
  • Vincent Lacroix
  • Marie-France Sagot
Part of the Lecture Notes in Computer Science book series (LNCS, volume 8126)

Abstract

We present a new algorithm for enumerating bubbles with length constraints in directed graphs. This problem arises in transcriptomics, where the question is to identify all alternative splicing events present in a sample of mRNAs sequenced by RNA-seq. This is the first polynomial-delay algorithm for this problem and we show that in practice, it is faster than previous approaches. This enables us to deal with larger instances and therefore to discover novel alternative splicing events, especially long ones, that were previously overseen using existing methods.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    KisSplice’s manual (2013), http://kissplice.prabi.fr/documentation
  2. 2.
    Ahuja, R.K., Mehlhorn, K., Orlin, J.B., Tarjan, R.E.: Faster algorithms for the Shortest Path Problem. J. ACM 37, 213–223 (1990)MathSciNetMATHCrossRefGoogle Scholar
  3. 3.
    Birmelé, E., Crescenzi, P., Ferreira, R.A., Grossi, R., Lacroix, V., Marino, A., Pisanti, N., Sacomoto, G.A.T., Sagot, M.-F.: Efficient bubble enumeration in directed graphs. In: Calderón-Benavides, L., González-Caro, C., Chávez, E., Ziviani, N. (eds.) SPIRE 2012. LNCS, vol. 7608, pp. 118–129. Springer, Heidelberg (2012)CrossRefGoogle Scholar
  4. 4.
    Chen, M., Chowdhury, R.A., Ramachandran, V., Roche, D.L., Tong, L.: Priority Queues and Dijkstra’s Algorithm. Technical Report TR-07-54 (2007)Google Scholar
  5. 5.
    Chikhi, R., Rizk, G.: Space-efficient and exact de bruijn graph representation based on a bloom filter. In: Raphael, B., Tang, J. (eds.) WABI 2012. LNCS, vol. 7534, pp. 236–248. Springer, Heidelberg (2012)CrossRefGoogle Scholar
  6. 6.
    Cormen, T.H., Stein, C., Rivest, R.L., Leiserson, C.E.: Introduction to Algorithms, 2nd edn. McGraw-Hill Higher Education (2001)Google Scholar
  7. 7.
    Grabherr, M.G., Haas, B.J., Yassour, M., Levin, J.Z., Thompson, D.A., et al.: Full-length transcriptome assembly from RNA-seq data without a reference genome. Nat. Biotechnol. 29, 644–652 (2011)CrossRefGoogle Scholar
  8. 8.
    Iqbal, Z., Caccamo, M., Turner, I., Flicek, P., McVean, G.: De novo assembly and genotyping of variants using colored de Bruijn graphs. Nat. Genetics (2012)Google Scholar
  9. 9.
    Li, C.-L., McCormick, S.T., Simchi-Levi, D.: The complexity of finding two disjoint paths with min-max objective function. Disc. Appl. Math. (1990)Google Scholar
  10. 10.
    Mortazavi, A., Williams, B., McCue, K., Schaeffer, L., Wold, B.: Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nat. Methods 5, 621–628 (2008)CrossRefGoogle Scholar
  11. 11.
    Pruitt, K., Tatusova, T., Klimke, W., Maglott, D.: NCBI reference sequences: current status, policy and new initiatives. Nucleic Acids Research 37(Database-Issue), 32–36 (2009)CrossRefGoogle Scholar
  12. 12.
    Robertson, G., Schein, J., Chiu, R., Corbett, R., et al.: De novo assembly and analysis of RNA-seq data. Nat. Methods 7, 909–912 (2010)CrossRefGoogle Scholar
  13. 13.
    Sacomoto, G.A.T., Kielbassa, J., Chikhi, R., Uricaru, R., Antoniou, P., Sagot, M.-F., Peterlongo, P., Lacroix, V.: Kissplice: de-novo calling alternative splicing events from RNA-seq data. BMC Bioinformatics 13, S5 (2012)Google Scholar
  14. 14.
    Schulz, M.H., Zerbino, D.R., Vingron, M., Birney, E.: Oases: robust de novo RNA-seq assembly across the dynamic range of expression levels. Bioinformatics 28, 1086–1092 (2012)CrossRefGoogle Scholar
  15. 15.
    Wang, E., Sandberg, R., Luo, S., Khrebtukova, I., Zhang, L., Mayr, C., Kingsmore, S., Schroth, G.P., Burge, C.: Alternative isoform regulation in human tissue transcriptomes. Nature 456(7221), 470–476 (2008)CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Gustavo Sacomoto
    • 1
    • 2
    • 3
  • Vincent Lacroix
    • 1
    • 2
    • 3
  • Marie-France Sagot
    • 1
    • 2
    • 3
  1. 1.INRIA Rhône-AlpesMontbonnot Saint-MartinFrance
  2. 2.Université de LyonLyonFrance
  3. 3.CNRS, UMR5558, Laboratoire de Biométrie et Biologie ÉvolutiveUniversité Lyon 1VilleurbanneFrance

Personalised recommendations