ArticlePloS one2011
A comprehensive benchmark study of multiple sequence alignment methods: current challenges and future perspectives.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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89 citing papers in PubMed.
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- Protein language model identifies disordered, conserved motifs implicated in phase separation.eLife · 2025Article
- ProtMamba: a homology-aware but alignment-free protein state space model.Bioinformatics (Oxford, England) · 2025Article
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- PRIEST: predicting viral mutations with immune escape capability of SARS-CoV-2 using temporal evolutionary information.Briefings in bioinformatics · 2024Article
- EMMA: a new method for computing multiple sequence alignments given a constraint subset alignment.Algorithms for molecular biology : AMB · 2023Article
- CoreDetector: a flexible and efficient program for core-genome alignment of evolutionary diverse genomes.Bioinformatics (Oxford, England) · 2023Article
- Pipeline for transferring annotations between proteins beyond globular domains.Protein science : a publication of the Protein Society · 2023Article
- Genome structure-based Juglandaceae phylogenies contradict alignment-based phylogenies and substitution rates vary with DNA repair genes.Nature communications · 2023Article
- The difficulty of aligning intrinsically disordered protein sequences as assessed by conservation and phylogeny.PloS one · 2023Article
- On closing the inopportune gap with consistency transformation and iterative refinement.PloS one · 2023Article
- WITCH-NG: efficient and accurate alignment of datasets with sequence length heterogeneity.Bioinformatics advances · 2023Article
- Boosting the Full Potential of PyMOL with Structural Biology Plugins.Biomolecules · 2022Review
- Accuracy of multiple sequence alignment methods in the reconstruction of transposable element families.NAR genomics and bioinformatics · 2022Article
- Application of the MAHDS Method for Multiple Alignment of Highly Diverged Amino Acid Sequences.International journal of molecular sciences · 2022Article
29 more citing papers are in PubMed but not listed here.
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4 authors.
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Abstract
Multiple comparison or alignmentof protein sequences has become a fundamental tool in many different domains in modern molecular biology, from evolutionary studies to prediction of 2D/3D structure, molecular function and inter-molecular interactions etc. By placing the sequence in the framework of the overall family, multiple alignments can be used to identify conserved features and to highlight differences or specificities. In this paper, we describe a comprehensive evaluation of many of the most popular methods for multiple sequence alignment (MSA), based on a new benchmark test set. The benchmark is designed to represent typical problems encountered when aligning the large protein sequence sets that result from today's high throughput biotechnologies. We show that alignmentmethods have significantly progressed and can now identify most of the shared sequence features that determine the broad molecular function(s) of a protein family, even for divergent sequences. However,we have identified a number of important challenges. First, the locally conserved regions, that reflect functional specificities or that modulate a protein's function in a given cellular context,are less well aligned. Second, motifs in natively disordered regions are often misaligned. Third, the badly predicted or fragmentary protein sequences, which make up a large proportion of today's databases, lead to a significant number of alignment errors. Based on this study, we demonstrate that the existing MSA methods can be exploited in combination to improve alignment accuracy, although novel approaches will still be needed to fully explore the most difficult regions. We then propose knowledge-enabled, dynamic solutions that will hopefully pave the way to enhanced alignment construction and exploitation in future evolutionary systems biology studies.
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