Abstract
In mass spectrometry-based de novo protein sequencing, it is hard to complete the sequence of the whole protein. Motivated by this we study the (one-sided) problem of filling a protein scaffold \(\mathcal{S}\) with some missing amino acids, given a sequence of contigs none of which is allowed to be altered, with respect to a complete reference protein \(\mathcal{P}\) of length n, such that the BLOSUM62 score between \(\mathcal{P}\) and the filled sequence \(\mathcal{S}'\) is maximized. We show that this problem is polynomial-time solvable in \(O(n^{26})\) time. We also consider the case when the contigs are not of high quality and they are concatenated into an (incomplete) sequence \(\mathcal{I}\), where the missing amino acids can be inserted anywhere in \(\mathcal{I}\) to obtain \(\mathcal{I}'\), such that the BLOSUM62 score between \(\mathcal{P}\) and \(\mathcal{I}'\) is maximized. We show that this problem is polynomial-time solvable in \(O(n^{22})\) time. Due to the high running time, both of these algorithms are impractical, we hence present several algorithms based on greedy and local search, trying to solve the problems practically. The empirical results show that the algorithms can fill protein scaffolds almost perfectly, provided that a good pair of scaffold and reference are given.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Bandeira, N., Pham, V., Pevzner, P., Arnott, D., Lill, J.: Beyond Edman degradation: automated de novo protein sequencing of monoclonal antibodies. Nat. Biotechnol. 26(12), 1336–1338 (2008)
Bandeira, N., Tang, H., Bafna, V., Pevzner, P.: Shotgun protein sequencing by tandem mass spectra assembly. Anal. Chem. 76, 7221–7233 (2004)
Bulteau, L., Carrieri, A.P., Dondi, R.: Fixed-parameter algorithms for scaffold filling. Theo. Comput. Sci. 568, 72–83 (2015)
Henikoff, S., Henikoff, J.: Amino acid substitution matrices from protein blocks. PNAS 89(22), 10915–10919 (1992)
Jiang, H., Zhong, F., Zhu, B.: Filling scaffolds with gene repetitions: maximizing the number of adjacencies. In: Giancarlo, R., Manzini, G. (eds.) CPM 2011. LNCS, vol. 6661, pp. 55–64. Springer, Heidelberg (2011)
Jiang, H., Zheng, C., Sankoff, D., Zhu, B.: Scaffold filling under the breakpoint and related distances. IEEE/ACM Trans. Comput. Biol. Bioinf. 9(4), 1220–1229 (2012)
Jiang, H., Ma, J., Luan, J., Zhu, D.: Approximation and nonapproximability for the one-sided scaffold filling problem. In: Xu, D., Du, D., Du, D. (eds.) COCOON 2015. LNCS, vol. 9198, pp. 251–263. Springer, Heidelberg (2015)
Liu, N., Jiang, H., Zhu, D., Zhu, B.: An improved approximation algorithm for scaffold filling to maximize the common adjacencies. IEEE/ACM Trans. Comput. Biol. Bioinf. 10(4), 905–913 (2013)
Liu, N., Zhu, D., Jiang, H., Zhu, B.: A 1.5-approximation algorithm for two-sided scaffold filling. Algorithmica 74(1), 91–116 (2016)
Liu, X., Han, Y., Yuen, D., Ma, B.: Automated protein (re)sequencing with MS/MS and a homologous database yields almost full coverage and accuracy. Bioinformatics 25, 2174–2180 (2009)
Liu, X., Dekker, L., Wu, S., Vanduijn, M., Luider, T., Tolic, N., Kou, Q., Dvorkin, M., Alexandrova, S., Vyatkina, K., Pasa-Tolic, L., Pevzner, P.: De Novo protein sequencing by combining top-down and bottom-up tandem mass spectra. J. Proteome Res. 13, 3241–3248 (2014)
Ma, B., Zhang, K., Hendrie, C., Liang, C., Li, M., Doherty-Kirby, A., Lajoie, G.: PEAKS: powerful software for peptide de novo sequencing by tandem mass spectrometry. Rapid Commun. Mass Spectrom. 17(20), 2337–2342 (2003)
Ma, B., Zhang, K., Liang, C.: An effective algorithm for peptide de novo sequencing from MA/MS spectra. J. Comput. Syst. Sci. 70(3), 418–430 (2005)
Muñoz, A., Zheng, C., Zhu, Q., Albert, V., Rounsley, S., Sankoff, D.: Scaffold filling, contig fusion and gene order comparison. BMC Bioinf. 11, 304 (2010)
Needleman, S., Wunsch, C.: A general method applicable to the search for similarities in the amino acid sequence of two proteins. J. Mol. Biol. 48(3), 443–453 (1970)
Pietrokovski, S., Henikoff, J., Henikoff, S.: The Blocks database - a system for protein classification. Nucl. Acids Res. 24(1), 197–200 (1996)
Acknowledgments
This research is partially supported by NSF of China under grant 60928006 and by the Opening Fund of Top Key Discipline of Computer Software and Theory in Zhejiang Provincial Colleges at Zhejiang Normal University. We also thank anonymous reviewers for several useful comments.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Appendix
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this paper
Cite this paper
Qingge, L., Liu, X., Zhong, F., Zhu, B. (2016). Filling a Protein Scaffold with a Reference. In: Bourgeois, A., Skums, P., Wan, X., Zelikovsky, A. (eds) Bioinformatics Research and Applications. ISBRA 2016. Lecture Notes in Computer Science(), vol 9683. Springer, Cham. https://doi.org/10.1007/978-3-319-38782-6_15
Download citation
DOI: https://doi.org/10.1007/978-3-319-38782-6_15
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-38781-9
Online ISBN: 978-3-319-38782-6
eBook Packages: Computer ScienceComputer Science (R0)