Abstract
The de novo assembly of genomes from high-throughput short reads is an active area of research. Several promising methods have been recently developed, with applicability largely restricted to the smaller and less complex bacterial genomes. In this paper, we present a method for assembling large genomes from high-coverage paired short reads. Our method exploits large distributed memory and parallelism available on multiprocessor systems to handle memory-intensive phases of the algorithm, effectively allowing scaling to large genomes. We present parallel algorithms to construct a bidirected string graph that is several orders of magnitude smaller than the raw sequence data and to extract features from paired reads. We also present a heuristic method that uses these features to guide the extension of partial graph traversals corresponding to large genomic contigs. In addition, we propose a simple model for error correction and derive a lower bound on the coverage needed for its use. We present a validation of our framework with short reads from D. melanogaster and S. cervisiae synthetically generated at 300-fold coverage. Assembly of the D. melanogaster genome resulted in large contigs (50% of the genome covered by contigs larger than 102Kb), accurate to 99.9% of the bases, in under 4 hours of wall clock time on a 512-node Blue Gene/L.
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References
Bennet, S.: Solexa ltd. Pharmacogenomics 5(4), 433–438 (2004)
Bentley, D.R., Balasubramanian, S., Swerdlow, H.P., Smith, G.P.: Accurate whole human genome sequencing using reversible terminator chemistry. Nature 456, 53–59 (2008)
Butler, J., MacCallum, I., Kleber, M., Shlyakhter, I.A., Belmonte, M.K., Lander, E.S., Nusbaum, C.N., Jaffe, D.B.: ALLPATHS: De novo assembly of whole-genome shotgun microreads. Genome Research 18, 810–820 (2008)
Chaisson, M.J., Pevzner, P.A.: Short fragment assembly of bacterial genomes. Genome Research 18, 324–330 (2008)
Dohm, J.C., Lottaz, C., Borodina, T., Himmelbauer, H.: SHARCGS, a fast and highly accurate short-read assembly algorithm for de novo genomic sequencing. Genome Research 17, 1697–1706 (2007)
Helman, D.R., Ja’Ja’, J., Bader, D.A.: A new deterministic parallel sorting algorithm with an experimental evaluation. Journal of Experimental Algorithms 3, 4 (1998)
Hernandez, D., Francois, P., Farinelli, L., Osteras, M., Schrenzel, J.: De novo bacterial genome sequencing: Millions of very short reads assembled on a desktop computer. Genome Research 18, 802–809 (2008)
Hossain, S., Azimi, N., Skiena, S.: Crystallizing short-read assemblies around lone Sanger reads. Bioinformatics (2009)
Idury, R.M., Waterman, M.S.: A new algorithm for DNA sequence assembly. Journal of Computational Biology 2, 291–306 (1995)
Jackson, B.G., Aluru, S.: Parallel construction of bidirected string graphs for genome assembly. In: Proceedings of the International Conference on Parallel Processsing, pp. 346–353 (2008)
Jackson, B.G., Schanble, P.S., Aluru, S.: Parallel short sequence assembly of transcriptomes. BMC Bioinformatics 10, S14 (2009)
Kurtz, S., Phillippy, A., Delcher, A.L., Smoot, M., Shumway, M., Antonescu, C., Salzberg, S.L.: Versatile and open software for comparing large genomes. Genome Biology 5 (2004)
Margulies, M., Egholm, M.: Genome sequencing in open microfabricated high density picoliter reactors. Nature 437(7054), 376–380 (2005)
Medvedev, P., Brudno, M.: Ab initio whole genome shotgun assembly with mated short reads. In: Vingron, M., Wong, L. (eds.) RECOMB 2008. LNCS (LNBI), vol. 4955, pp. 50–64. Springer, Heidelberg (2008)
Myers, E.W.: The fragment assembly string graph. Bioinformatics 21, ii79–ii85 (2005)
Ossowski1, S., Schneeberger1, K., Clark, R.M., Lanz, C., Warthmann, N., Weigel, D.: Sequencing of natural strains of arabidopsis thaliana with short reads. Genome Research (preprint) (2008)
Pandey, V., Nutter, R.C., Prediger, E.: Applied Biosystems SOLiD System: Ligation-Based Sequencing. Wiley, Chichester (2008)
Pevzner, P.A., Tang, H., Waterman, M.S.: Fragment assembly with double-barreled data. Proceedings of the National Academy of Sciences 98(17), 9748–9753 (2001)
Wang, J., Wang, W., Li, R., Li, Y.: The diploid genome sequence of an Asian individual. Nature 456, 60–65 (2008)
Warren, R.L., Sutton, G.G., Jones, S.J.M., Holt, R.A.: Assembling millions of short DNA sequences using SSAKE. Bioinformatics 23, 500–501 (2007)
Wicker, T., Narechania, A., Sabot, F., Vu, G.T.H., Graner, A., Ware, D., Stein, N.: Low-pass shotgun sequencing of the barley genome facilitates rapid identification of genes, conserved non-coding sequences and novel repeats. BMC Genomics 9, 518 (2008)
Business Wire. Helicos biosciences enters molecular diagnostics collaboration with renowned research center to sequence cancer-associated genes. Genetic Engineering and Biotechnology News (2008)
Zerbino, D., Birney, E.: Velvet: Algorithms for de novo short read assembly using de Bruijn graphs. Genome Research 18, 821–829 (2008)
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Jackson, B.G., Schnable, P.S., Aluru, S. (2009). Assembly of Large Genomes from Paired Short Reads. In: Rajasekaran, S. (eds) Bioinformatics and Computational Biology. BICoB 2009. Lecture Notes in Computer Science(), vol 5462. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-00727-9_5
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DOI: https://doi.org/10.1007/978-3-642-00727-9_5
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