Efficient representation of uncertainty in multiple sequence alignments using directed acyclic graphs

Herman, Joseph L and Novák, Ádám and Lyngsø, Rune and Szabó, Adrienn and Miklós, István (2015) Efficient representation of uncertainty in multiple sequence alignments using directed acyclic graphs. BMC BIOINFORMATICS, 16 (108). pp. 1-26. ISSN 1471-2105 10.1186/s12859-015-0516-1

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Abstract

Background A standard procedure in many areas of bioinformatics is to use a single multiple sequence alignment (MSA) as the basis for various types of analysis. However, downstream results may be highly sensitive to the alignment used, and neglecting the uncertainty in the alignment can lead to significant bias in the resulting inference. In recent years, a number of approaches have been developed for probabilistic sampling of alignments, rather than simply generating a single optimum. However, this type of probabilistic information is currently not widely used in the context of downstream inference, since most existing algorithms are set up to make use of a single alignment. Results In this work we present a framework for representing a set of sampled alignments as a directed acyclic graph (DAG) whose nodes are alignment columns; each path through this DAG then represents a valid alignment. Since the probabilities of individual columns can be estimated from empirical frequencies, this approach enables sample-based estimation of posterior alignment probabilities. Moreover, due to conditional independencies between columns, the graph structure encodes a much larger set of alignments than the original set of sampled MSAs, such that the effective sample size is greatly increased. Conclusions The alignment DAG provides a natural way to represent a distribution in the space of MSAs, and allows for existing algorithms to be efficiently scaled up to operate on large sets of alignments. As an example, we show how this can be used to compute marginal probabilities for tree topologies, averaging over a very large number of MSAs. This framework can also be used to generate a statistically meaningful summary alignment; example applications show that this summary alignment is consistently more accurate than the majority of the alignment samples, leading to improvements in downstream tree inference. Implementations of the methods described in this article are available at http://statalign.github.io/WeaveAlign webcite.

Item Type: Article
Uncontrolled Keywords: Statistical alignment; MULTIPLE SEQUENCE ALIGNMENT; Alignment uncertainty; Alignment graphs
Subjects: Q Science > QA Mathematics and Computer Science > QA75 Electronic computers. Computer science / számítástechnika, számítógéptudomány
Divisions: Informatics Laboratory
SWORD Depositor: MTMT Injector
Depositing User: MTMT Injector
Date Deposited: 31 Jan 2016 08:40
Last Modified: 31 Jan 2016 08:40
URI: http://eprints.sztaki.hu/id/eprint/8556

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