Multiple Sequence Alignment

Multiple Sequence Alignment

This page is a placeholder, or under current development; it is here principally to establish the logical framework of the site. The material on this page is correct, but incomplete.

MSA: Multiple sequence alignments

 

Introductory reading

Caution: 2005 article.

Wallace et al. (2005) Multiple sequence alignments. Curr Opin Struct Biol 15:261-6. (pmid: 15963889)

[ PubMed ] [ DOI ] Multiple sequence alignments are very widely used in all areas of DNA and protein sequence analysis. The main methods that are still in use are based on 'progressive alignment' and date from the mid to late 1980s. Recently, some dramatic improvements have been made to the methodology with respect either to speed and capacity to deal with large numbers of sequences or to accuracy. There have also been some practical advances concerning how to combine three-dimensional structural information with primary sequences to give more accurate alignments, when structures are available.

 

Contents

Multiple Sequence Alignment - Lecture by Boris Steipe. BCH441 - 2011
MSA - Presentation by Nirvana Nursimulu, BCB410 - 2011

 

Exercises

Exercises - by Nirvana Nursimulu, BCB410 - 2011

 

Further reading and resources

Methods in Molecular Biology

Multiple Sequence Alignment Methods

Springer (2014)

Kim & Ma (2014) PSAR-align: improving multiple sequence alignment using probabilistic sampling. Bioinformatics 30:1010-2. (pmid: 24222208)

[ PubMed ] [ DOI ] SUMMARY: We developed PSAR-Align, a multiple sequence realignment tool that can refine a given multiple sequence alignment based on suboptimal alignments generated by probabilistic sampling. Our evaluation demonstrated that PSAR-Align is able to improve the results from various multiple sequence alignment tools. AVAILABILITY AND IMPLEMENTATION: The PSAR-Align source code (implemented mainly in C++) is freely available for download at http://bioen-compbio.bioen.illinois.edu/PSAR-Align.

Roshan (2014) Multiple sequence alignment using Probcons and Probalign. Methods Mol Biol 1079:147-53. (pmid: 24170400)

[ PubMed ] [ DOI ] Sequence alignment remains a fundamental task in bioinformatics. The literature contains programs that employ a host of exact and heuristic strategies available in computer science. Probcons was the first program to construct maximum expected accuracy sequence alignments with hidden Markov models and at the time of its publication achieved the highest accuracies on standard protein multiple alignment benchmarks. Probalign followed this strategy except that it used a partition function approach instead of hidden Markov models. Several programs employing both strategies have been published since then. In this chapter we describe Probcons and Probalign.

Taly et al. (2011) Using the T-Coffee package to build multiple sequence alignments of protein, RNA, DNA sequences and 3D structures. Nat Protoc 6:1669-82. (pmid: 21979275)

[ PubMed ] [ DOI ] T-Coffee (Tree-based consistency objective function for alignment evaluation) is a versatile multiple sequence alignment (MSA) method suitable for aligning most types of biological sequences. The main strength of T-Coffee is its ability to combine third party aligners and to integrate structural (or homology) information when building MSAs. The series of protocols presented here show how the package can be used to multiply align proteins, RNA and DNA sequences. The protein section shows how users can select the most suitable T-Coffee mode for their data set. Detailed protocols include T-Coffee, the default mode, M-Coffee, a meta version able to combine several third party aligners into one, PSI (position-specific iterated)-Coffee, the homology extended mode suitable for remote homologs and Expresso, the structure-based multiple aligner. We then also show how the T-RMSD (tree based on root mean square deviation) option can be used to produce a functionally informative structure-based clustering. RNA alignment procedures are described for using R-Coffee, a mode able to use predicted RNA secondary structures when aligning RNA sequences. DNA alignments are illustrated with Pro-Coffee, a multiple aligner specific of promoter regions. We also present some of the many reformatting utilities bundled with T-Coffee. The package is an open-source freeware available from http://www.tcoffee.org/.

Peng & Xu (2011) A multiple-template approach to protein threading. Proteins 79:1930-9. (pmid: 21465564)

[ PubMed ] [ DOI ] Most threading methods predict the structure of a protein using only a single template. Due to the increasing number of solved structures, a protein without solved structure is very likely to have more than one similar template structures. Therefore, a natural question to ask is if we can improve modeling accuracy using multiple templates. This article describes a new multiple-template threading method to answer this question. At the heart of this multiple-template threading method is a novel probabilistic-consistency algorithm that can accurately align a single protein sequence simultaneously to multiple templates. Experimental results indicate that our multiple-template method can improve pairwise sequence-template alignment accuracy and generate models with better quality than single-template models even if they are built from the best single templates (P-value <10(-6)) while many popular multiple sequence/structure alignment tools fail to do so. The underlying reason is that our probabilistic-consistency algorithm can generate accurate multiple sequence/template alignments. In another word, without an accurate multiple sequence/template alignment, the modeling accuracy cannot be improved by simply using multiple templates to increase alignment coverage. Blindly tested on the CASP9 targets with more than one good template structures, our method outperforms all other CASP9 servers except two (Zhang-Server and QUARK of the same group). Our probabilistic-consistency algorithm can possibly be extended to align multiple protein/RNA sequences and structures.

Edgar (2004) MUSCLE: a multiple sequence alignment method with reduced time and space complexity. BMC Bioinformatics 5:113. (pmid: 15318951)

[ PubMed ] [ DOI ] BACKGROUND: In a previous paper, we introduced MUSCLE, a new program for creating multiple alignments of protein sequences, giving a brief summary of the algorithm and showing MUSCLE to achieve the highest scores reported to date on four alignment accuracy benchmarks. Here we present a more complete discussion of the algorithm, describing several previously unpublished techniques that improve biological accuracy and / or computational complexity. We introduce a new option, MUSCLE-fast, designed for high-throughput applications. We also describe a new protocol for evaluating objective functions that align two profiles. RESULTS: We compare the speed and accuracy of MUSCLE with CLUSTALW, Progressive POA and the MAFFT script FFTNS1, the fastest previously published program known to the author. Accuracy is measured using four benchmarks: BAliBASE, PREFAB, SABmark and SMART. We test three variants that offer highest accuracy (MUSCLE with default settings), highest speed (MUSCLE-fast), and a carefully chosen compromise between the two (MUSCLE-prog). We find MUSCLE-fast to be the fastest algorithm on all test sets, achieving average alignment accuracy similar to CLUSTALW in times that are typically two to three orders of magnitude less. MUSCLE-fast is able to align 1,000 sequences of average length 282 in 21 seconds on a current desktop computer. CONCLUSIONS: MUSCLE offers a range of options that provide improved speed and / or alignment accuracy compared with currently available programs. MUSCLE is freely available at http://www.drive5.com/muscle.

Katoh & Toh (2008) Recent developments in the MAFFT multiple sequence alignment program. Brief Bioinformatics 9:286-98. (pmid: 18372315)

[ PubMed ] [ DOI ] The accuracy and scalability of multiple sequence alignment (MSA) of DNAs and proteins have long been and are still important issues in bioinformatics. To rapidly construct a reasonable MSA, we developed the initial version of the MAFFT program in 2002. MSA software is now facing greater challenges in both scalability and accuracy than those of 5 years ago. As increasing amounts of sequence data are being generated by large-scale sequencing projects, scalability is now critical in many situations. The requirement of accuracy has also entered a new stage since the discovery of functional noncoding RNAs (ncRNAs); the secondary structure should be considered for constructing a high-quality alignment of distantly related ncRNAs. To deal with these problems, in 2007, we updated MAFFT to Version 6 with two new techniques: the PartTree algorithm and the Four-way consistency objective function. The former improved the scalability of progressive alignment and the latter improved the accuracy of ncRNA alignment. We review these and other techniques that MAFFT uses and suggest possible future directions of MSA software as a basis of comparative analyses. MAFFT is available at http://align.bmr.kyushu-u.ac.jp/mafft/software/.

Kemena & Notredame (2009) Upcoming challenges for multiple sequence alignment methods in the high-throughput era. Bioinformatics 25:2455-65. (pmid: 19648142)

[ PubMed ] [ DOI ] This review focuses on recent trends in multiple sequence alignment tools. It describes the latest algorithmic improvements including the extension of consistency-based methods to the problem of template-based multiple sequence alignments. Some results are presented suggesting that template-based methods are significantly more accurate than simpler alternative methods. The validation of existing methods is also discussed at length with the detailed description of recent results and some suggestions for future validation strategies. The last part of the review addresses future challenges for multiple sequence alignment methods in the genomic era, most notably the need to cope with very large sequences, the need to integrate large amounts of experimental data, the need to accurately align non-coding and non-transcribed sequences and finally, the need to integrate many alternative methods and approaches.

Chang et al. (2012) Accurate multiple sequence alignment of transmembrane proteins with PSI-Coffee. BMC Bioinformatics 13 Suppl 4:S1. (pmid: 22536955)

[ PubMed ] [ DOI ] BACKGROUND: Transmembrane proteins (TMPs) constitute about 20~30% of all protein coding genes. The relative lack of experimental structure has so far made it hard to develop specific alignment methods and the current state of the art (PRALINE™) only manages to recapitulate 50% of the positions in the reference alignments available from the BAliBASE2-ref7. METHODS: We show how homology extension can be adapted and combined with a consistency based approach in order to significantly improve the multiple sequence alignment of alpha-helical TMPs. TM-Coffee is a special mode of PSI-Coffee able to efficiently align TMPs, while using a reduced reference database for homology extension. RESULTS: Our benchmarking on BAliBASE2-ref7 alpha-helical TMPs shows a significant improvement over the most accurate methods such as MSAProbs, Kalign, PROMALS, MAFFT, ProbCons and PRALINE™. We also estimated the influence of the database used for homology extension and show that highly non-redundant UniRef databases can be used to obtain similar results at a significantly reduced computational cost over full protein databases. TM-Coffee is part of the T-Coffee package, a web server is also available from http://tcoffee.crg.cat/tmcoffee and a freeware open source code can be downloaded from http://www.tcoffee.org/Packages/Stable/Latest.