Alignment methods.pdf

Alignment methods.pdf - Chapter 7 Alignment Methods...

Info icon This preview shows pages 1–3. Sign up to view the full content.

Chapter 7 Alignment Methods: Strategies, Challenges, Benchmarking, and Comparative Overview Ari Lo ¨ytynoja Abstract Comparative evolutionary analyses of molecular sequences are solely based on the identities and differences detected between homologous characters. Errors in this homology statement, that is errors in the align- ment of the sequences, are likely to lead to errors in the downstream analyses. Sequence alignment and phylogenetic inference are tightly connected and many popular alignment programs use the phylogeny to divide the alignment problem into smaller tasks. They then neglect the phylogenetic tree, however, and produce alignments that are not evolutionarily meaningful. The use of phylogeny-aware methods reduces the error but the resulting alignments, with evolutionarily correct representation of homology, can challenge the existing practices and methods for viewing and visualising the sequences. The inter- dependency of alignment and phylogeny can be resolved by joint estimation of the two; methods based on statistical models allow for inferring the alignment parameters from the data and correctly take into account the uncertainty of the solution but remain computationally challenging. Widely used alignment methods are based on heuristic algorithms and unlikely to find globally optimal solutions. The whole concept of one correct alignment for the sequences is questionable, however, as there typically exist vast numbers of alternative, roughly equally good alignments that should also be considered. This uncertainty is hidden by many popular alignment programs and is rarely correctly taken into account in the downstream analyses. The quest for finding and improving the alignment solution is complicated by the lack of suitable measures of alignment goodness. The difficulty of comparing alternative solutions also affects benchmarks of alignment methods and the results strongly depend on the measure used. As the effects of alignment error cannot be predicted, comparing the alignments’ performance in downstream analyses is recommended. Key words: Character homology, Evolutionary sequence alignment, Dynamic programming, Insertions and deletions, Alignment correctness 1. Introduction Sequence alignment is a central tool in molecular biology. Signifi- cant similarity between sequences typically implies their structural and functional similarity and allows assignment of knowledge from Maria Anisimova (ed.), Evolutionary Genomics: Statistical and Computational Methods, Volume 1 , Methods in Molecular Biology, vol. 855, DOI 10.1007/978-1-61779-582-4_7, # Springer Science+Business Media, LLC 2012 203
Image of page 1

Info icon This preview has intentionally blurred sections. Sign up to view the full version.

better studied molecules to unknown ones. Comparisons of multi- ple related sequences help to understand the constraints affecting their evolution and are informative for their structural and func- tional studies. Alignment is, however, an especially crucial part of evolutionary and phylogenetic analyses of molecular sequences, as these inferences are solely based on the identities and differences detected between evolutionarily homologous characters. Indeed,
Image of page 2
Image of page 3
This is the end of the preview. Sign up to access the rest of the document.
  • Fall '12
  • BruceCochrane

{[ snackBarMessage ]}

What students are saying

  • Left Quote Icon

    As a current student on this bumpy collegiate pathway, I stumbled upon Course Hero, where I can find study resources for nearly all my courses, get online help from tutors 24/7, and even share my old projects, papers, and lecture notes with other students.

    Student Picture

    Kiran Temple University Fox School of Business ‘17, Course Hero Intern

  • Left Quote Icon

    I cannot even describe how much Course Hero helped me this summer. It’s truly become something I can always rely on and help me. In the end, I was not only able to survive summer classes, but I was able to thrive thanks to Course Hero.

    Student Picture

    Dana University of Pennsylvania ‘17, Course Hero Intern

  • Left Quote Icon

    The ability to access any university’s resources through Course Hero proved invaluable in my case. I was behind on Tulane coursework and actually used UCLA’s materials to help me move forward and get everything together on time.

    Student Picture

    Jill Tulane University ‘16, Course Hero Intern