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Nucleic Acids Res. 2015 Jul 1;43(W1):W7-14. doi: 10.1093/nar/gkv318. Epub 2015 Apr 16.

GUIDANCE2: accurate detection of unreliable alignment regions accounting for the uncertainty of multiple parameters.

Author information

1
Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv 6997801, Israel.
2
Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan Computational Biology Research Center, The National Institute of Advanced Industrial Science and Technology (AIST), Tokyo 135-0064, Japan.
3
Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv 6997801, Israel talp@post.tau.ac.il.

Abstract

Inference of multiple sequence alignments (MSAs) is a critical part of phylogenetic and comparative genomics studies. However, from the same set of sequences different MSAs are often inferred, depending on the methodologies used and the assumed parameters. Much effort has recently been devoted to improving the ability to identify unreliable alignment regions. Detecting such unreliable regions was previously shown to be important for downstream analyses relying on MSAs, such as the detection of positive selection. Here we developed GUIDANCE2, a new integrative methodology that accounts for: (i) uncertainty in the process of indel formation, (ii) uncertainty in the assumed guide tree and (iii) co-optimal solutions in the pairwise alignments, used as building blocks in progressive alignment algorithms. We compared GUIDANCE2 with seven methodologies to detect unreliable MSA regions using extensive simulations and empirical benchmarks. We show that GUIDANCE2 outperforms all previously developed methodologies. Furthermore, GUIDANCE2 also provides a set of alternative MSAs which can be useful for downstream analyses. The novel algorithm is implemented as a web-server, available at: http://guidance.tau.ac.il.

PMID:
25883146
PMCID:
PMC4489236
DOI:
10.1093/nar/gkv318
[Indexed for MEDLINE]
Free PMC Article

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