Chapter 6 Align related sequences

Recent papers provide in-depth analysis of the spike protein on the base of structure, sequence, and computation (Walls et al. (2020), Wang et al. (2020), Lokman et al. (2020)) amongst the vast number of released papers.

Aligning multiple sequences that are longer can be challenging even for sequences that are relatively similar. A few decades ago manual adjustments were inevitable. Nowadays software with combined powerful algorithms and methods can give very good results. Human intervention by manual adjustments might still be needed in some areas of lesser similarity, but it may be that we just cannot know.

This section is meant to explore how to align a sequence of the SARS_CoV-2 spike glycoprotein S to other related spike sequences based on examples in the cited papers.

To this aim one could use web services but that is not the goal of this tutorial. For those interested in web services, the aligners proposed on this page are worth checking: https://bip.weizmann.ac.il/toolbox/structure/seq_align.htm (Archived: 13OCT2016 https://bit.ly/37SlLKV)

For the exercise below we’ll use TCoffee (Notredame, Higgins, and Heringa (2000), Thompson (2009)).

References

Lokman, S. M., M. Rasheduzzaman, A. Salauddin, R. Barua, A. Y. Tanzina, M. H. Rumi, M. I. Hossain, A. M. A. M. Z. Siddiki, A. Mannan, and M. M. Hasan. 2020. “Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: A computational biology approach.” Infect. Genet. Evol. 84 (June): 104389. https://doi.org/https://doi.org/10.1016/j.meegid.2020.104389.

Notredame, C., D. G. Higgins, and J. Heringa. 2000. “T-Coffee: A novel method for fast and accurate multiple sequence alignment.” J. Mol. Biol. 302 (1): 205–17. https://doi.org/https://dx.doi.org/10.1006/jmbi.2000.4042.

Thompson, Steven. 2009. “An Introduction to Multiple Sequence Alignment — and the T-Coffee Shop. Beyond Just Aligning Sequences: How Good Can You Make Your Alignment, and so What?” In Bioinformatics for Systems Biology, 283–313. https://doi.org/10.1007/978-1-59745-440-7_15.

Walls, A. C., Y. J. Park, M. A. Tortorici, A. Wall, A. T. McGuire, and D. Veesler. 2020. “Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein.” Cell 181 (2): 281–92. https://doi.org/https://dx.doi.org/10.1016/j.cell.2020.02.058.

Wang, Q., Y. Zhang, L. Wu, S. Niu, C. Song, Z. Zhang, G. Lu, et al. 2020. “Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2.” Cell 181 (4): 894–904. https://doi.org/https://dx.doi.org/10.1016/j.cell.2020.03.045.