Abstract
Scaffolding, the problem of ordering and orienting contigs, typically using paired-end reads, is a crucial step in the assembly of high-quality draft genomes. Even as sequencing technologies and mate-pair protocols have improved significantly, scaffolding programs still rely on heuristics, with no gaurantees on the quality of the solution. In this work we explored the feasibility of an exact solution for scaffolding and present a first fixed-parameter tractable solution for assembly (Opera). We also describe a graph contraction procedure that allows the solution to scale to large scaffolding problems and demonstrate this by scaffolding several large real and synthetic datasets. In comparisons with existing scaffolders, Opera simultaneously produced longer and more accurate scaffolds demonstrating the utility of an exact approach. Opera also incorporates an exact quadratic programming formulation to precisely compute gap sizes.
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References
Ng, P., Tan, J.J., Ooi, H.S., et al.: Multiplex sequencing of paired-end ditags (MS-PET): A strategy for the ultra-high-throughput analysis of transcriptomes and genomes. Nucleic Acids Research 34, e84 (2006)
Eid, J., Fehr, A., Gray, J., et al.: Real-time DNA sequencing from single polymerase molecules. Science 323(5910), 133–138 (2009)
Dayarian, A., Michael, T.P., Sengupta, A.M.: SOPRA: Scaffolding algorithm for paired reads via statistical optimization. BMC Bioinformatics 11(345) (2010)
Chaisson, M.J., Brinza, D., Pevzner, P.A.: De novo fragment assembly with short mate-paired reads: does the read length matter? Genome Research 19, 336–346 (2009)
Zerbino, D.R., McEwen, G.K., Marguiles, E.H., Birney, E.: Pebble and rock band: heuristic resolution of repeats and scaffolding in the velvet short-read de novo assembler. PLoS ONEÂ 4(12) (2009)
Huson, D.H., Reinert, K., Myers, E.W.: The greedy path-merging algorithm for contig scaffolding. Journal of the ACM 49(5), 603–615 (2002)
Myers, E.W., Sutton, G.G., Delcher, A.L., et al.: A whole-genome assembly of Drosophila. Science 287(5461), 2196–2204 (2000)
Kent, W.J., Haussler, D.: Assembly of the working draft of the human genome with GigAssembler. Genome Research 11, 1541–1548 (2001)
Pevzner, P.A., Tang, H.: Fragment assembly with double-barreled data. Bioinformatics 17(S1), 225–233 (2001)
Pop, M., Kosack, S.D., Salzberg, S.L.: Hierarchical scaffolding with bambus. Genome Research 14, 149–159 (2004)
Mullikin, J.C., Ning, Z.: The phusion assembler. Genome Research 13, 81–90 (2003)
Jaffe, D.B., Butler, J., Gnerre, S., et al.: Whole-genome sequence assembly for mammalian genomes: Arachne 2. Genome Research 13, 91–96 (2003)
Aparicio, S., Chapma, J., Stupka, E., et al.: Whole-genome shotgun assembly and analysis of the genome of Fugu rubripes. Science 297, 1301–1310 (2002)
Pop, M., Phillipy, A., Delcher, A.L., Salzberg, S.L.: Comparative genome assembly. Briefings in Bioinformatics 5(3), 237–248 (2004)
Richter, D.C., Schuster, S.C., Huson, D.H.: OSLay: optimal syntenic layout of unfinished assemblies. Bioinformatics 23(13), 1573–1579 (2007)
Husemann, P., Stoye, J.: Phylogenetic comparative assembly. Algorithms for Molecular Biology 5(3) (2010)
Nagarajan, N., Read, T.D., Pop, M.: Scaffolding and validation of bacterial genome assemblies using optical restriction maps. Bioinformatics 24(10), 1229–1235 (2008)
Pop, M.: Shotgun sequence assembly. Advances in Computers 60 (2004)
Saxe, J.: Dynamic programming algorithms for recognizing small-bandwidth graphs in polynomial time. SIAM J. on Algebraic and Discrete Methodd 1(4), 363–369 (1980)
Goldfarb, D., Idnani, A.: A numerically stable dual method for solving strictly convex quadratic programs. Mathematical Programming 27 (1983)
Richter, D.C., Ott, F., Schmid, R., Huson, D.H.: Metasim: a sequencing simulator for genomics and metagenomics. PloS One 3(10) (2008)
MacCallum, I., Przybylksi, D., Gnerre, S., et al.: ALLPATHS2: small genomes assembled accurately and with high continuity from short paired reads. Genome Biology 10, R103 (2009)
Nandi, T., Ong, C., Singh, A.P., et al.: A genomic survey of positive selection in Burkholderia pseudomallei provides insights into the evolution of accidental virulence. PLoS Pathogens 6(4) (2010)
Kurtz, S.A., Phillippy, A., Delcher, A.L., et al.: Versatile and open software for comparing large genomes. Genome Biology 5, R12 (2004)
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Gao, S., Nagarajan, N., Sung, WK. (2011). Opera: Reconstructing Optimal Genomic Scaffolds with High-Throughput Paired-End Sequences. In: Bafna, V., Sahinalp, S.C. (eds) Research in Computational Molecular Biology. RECOMB 2011. Lecture Notes in Computer Science(), vol 6577. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-20036-6_40
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DOI: https://doi.org/10.1007/978-3-642-20036-6_40
Publisher Name: Springer, Berlin, Heidelberg
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