GUIDANCE2: accurate detection of unreliable alignment regions accounting for the uncertainty of multiple parameters
Open accessAbstract
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.
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GUIDANCE2 was used to remove unreliable coding sequence alignments and alignment positions.
“We used OrthoMCL (Li et al., 2003), which is a program that filters orthologous proteins, and GUIDANCE2 (Sela et al., 2015) to remove unreliable coding sequence (CDS) alignments and alignment positions.”
From Genomic and physiological mechanisms underlying skin plasticity during water to air transition in an amphibious fish (2020) · cites this paper as Sela et al., 2015
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- Authors
- Sela, I., Ashkenazy, H., Katoh, K., & Pupko, T.
- Affiliations
- Tel Aviv University (IL)
- Immunology Frontier Research Center, The University of Osaka (JP)
- Corresponding author
- Pupko, Tal
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-04-16
- Volume
- 43
- Issue
- W1
- Pages
- W7-W14
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC4489236
- OpenAlex
- W2074830661
- Cited by
- 835
- References
- 61
- Citations by year
- 2026: 37 · 2025: 60 · 2024: 74 · 2023: 71 · 2022: 92 · 2021: 119 · 2020: 126 · 2019: 82 · 2018: 78 · 2017: 57 · 2016: 34 · 2015: 4
- FWCI
- 25.05
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nucleic Acids Research (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- University of Pennsylvania
- Israel Science Foundation (1092/13)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fractal and DNA sequence analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- multiple sequence alignment, progressive alignment, positive selection detection, phylogenetics, comparative genomics
- MeSH terms
- Algorithms, Software, Sequence Alignment, Internet, Uncertainty
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