Abstract
Next Generation Sequencing (NGS) technologies are capable of reading millions of short DNA sequences both quickly and cheaply. While these technologies are already being used for resequencing individuals once a reference genome exists, it has not been shown if it is possible to use them for ab initio genome assembly. In this paper, we give a novel network flow-based algorithm that, by taking advantage of the high coverage provided by NGS, accurately estimates the copy counts of repeats in a genome. We also give a second algorithm that combines the predicted copy-counts with mate-pair data in order to assemble the reads into contigs. We run our algorithms on simulated read data from E. Coli and predict copy-counts with extremely high accuracy, while assembling long contigs.
This is a preview of subscription content, log in via an institution to check access.
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Ahuja, R.K., Magnanti, T.L., Orlin, J.B.: Network flows: theory, algorithms, and applications. Prentice-Hall, Inc., Upper Saddle River, NJ, USA (1993)
Appa, G., Kotnyek, B.: A bidirected generalization of network matrices. Networks 47(4), 185–198 (2006)
Batzoglou, S., Jaffe, D.B., Stanley, K., Butler, J., Gnerre, S., Mauceli, E., Berger, B., Mesirov, J.P., Lander, E.S.: Arachne: a whole-genome shotgun assembler. Genome Res. 12(1), 177–189 (2002)
Chaisson, M., Pevzner, P.A., Tang, H.: Fragment assembly with short reads. Bioinformatics 20(13), 2067–2074 (2004)
Chaisson, M.J., Pevzner, P.A.: Short read fragment assembly of bacterial genomes. Genome. Published online before print Doi:10.1101/gr.7088808 (2007)
Dohm, J., Lottaz, C., Borodina, T., Himmelbauer, H.: SHARCGS, a fast and highly accurate short-read assembly algorithm for de novo genomic sequencing. Genome Res. 17, 1697–1706 (2007)
Edmonds, J.: An introduction to matching. In: Notes of engineering summer conference, University of Michigan, Ann Arbor (1967)
Gabow, H.N.: An efficient reduction technique for degree-constrained subgraph and bidirected network flow problems. In: STOC, pp. 448–456 (1983)
Goldberg, A.V.: An efficient implementation of a scaling minimum-cost flow algorithm. J. Algorithms 22(1), 1–29 (1997)
Hochbaum, D.S.: Monotonizing linear programs with up to two nonzeroes per column. Oper. Res. Lett. 32(1), 49–58 (2004)
Chen, J., Skiena, S.: Assembly For Double-Ended Short-Read Sequencing Technologies. In: Mardis, E., Kim, S., Tang, H. (eds.) Advances in Genome Sequencing Technology and Algorithms, pp. 123–141. Artech House Publishers (2007)
Jeck, W.R., Reinhardt, J.A., Baltrus, D.A., Hickenbotham, M.T., Magrini, V., Mardis, E.R., Dangl, J.L., Jones, C.D.: Extending assembly of short DNA sequences to handle error. Bioinformatics 23, 2942–2944 (2007)
Kececioglu, J.D.: Exact and approximation algorithms for DNA sequence reconstruction. PhD thesis, University of Arizona, Tucson, AZ, USA (1992)
Medvedev, P., Georgiou, K., Myers, G., Brudno, M.: Computability of models for sequence assembly. In: WABI, pp. 289–301 (2007)
Myers, E.W.: The fragment assembly string graph. In: ECCB/JBI, p. 85 (2005)
Myers, E.W., Sutton, G.G., Delcher, A.L., Dew, I.M., Fasulo, D.P., Flanigan, M.J., Kravitz, S.A., Mobarry, C.M., Reinert, K.H.J., Remington, K.A., Anson, E.L., Bolanos, R.A., Chou, H.-H., Jordan, C.M., Halpern, A.L., Lonardi, S., Beasley, E.M., Brandon, R.C., Chen, L., Dunn, P.J., Lai, Z., Liang, Y., Nusskern, D.R., Zhan, M., Zhang, Q., Zheng, X., Rubin, G.M., Adams, M.D., Venter, J.C.: A Whole-Genome Assembly of Drosophila. Science 287, 2196–2204 (2000)
Pevzner, P.A., Tang, H., Waterman, M.S.: An Eulerian path approach to DNA fragment assembly. Proceedings of the National Academy of Sciences 98, 9748–9753 (2001)
Pevzner, P.A., Tang, H.: Fragment assembly with double-barreled data. In: ISMB (Supplement of Bioinformatics), pp. 225–233 (2001)
Pevzner, P.A., Tang, H., Tesler, G.: De novo repeat classification and fragment assembly. In: RECOMB, pp. 213–222 (2004)
Warren, R.L., Sutton, G.G., Jones, S.J., Holt, R.A.: Assembling millions of short DNA sequences using SSAKE. Bioinformatics 23, 500–501 (2007)
Author information
Authors and Affiliations
Editor information
Rights and permissions
Copyright information
© 2008 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Medvedev, P., Brudno, M. (2008). Ab Initio Whole Genome Shotgun Assembly with Mated Short Reads. In: Vingron, M., Wong, L. (eds) Research in Computational Molecular Biology. RECOMB 2008. Lecture Notes in Computer Science(), vol 4955. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-78839-3_5
Download citation
DOI: https://doi.org/10.1007/978-3-540-78839-3_5
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-78838-6
Online ISBN: 978-3-540-78839-3
eBook Packages: Computer ScienceComputer Science (R0)