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      Upcoming challenges for multiple sequence alignment methods in the high-throughput era

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      Bioinformatics
      Oxford University Press

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          Abstract

          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.

          Contact: cedric.notredame@ 123456crg.es

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          Most cited references64

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          A small molecule-kinase interaction map for clinical kinase inhibitors.

          Kinase inhibitors show great promise as a new class of therapeutics. Here we describe an efficient way to determine kinase inhibitor specificity by measuring binding of small molecules to the ATP site of kinases. We have profiled 20 kinase inhibitors, including 16 that are approved drugs or in clinical development, against a panel of 119 protein kinases. We find that specificity varies widely and is not strongly correlated with chemical structure or the identity of the intended target. Many novel interactions were identified, including tight binding of the p38 inhibitor BIRB-796 to an imatinib-resistant variant of the ABL kinase, and binding of imatinib to the SRC-family kinase LCK. We also show that mutations in the epidermal growth factor receptor (EGFR) found in gefitinib-responsive patients do not affect the binding affinity of gefitinib or erlotinib. Our results represent a systematic small molecule-protein interaction map for clinical compounds across a large number of related proteins.
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            Protein structure alignment by incremental combinatorial extension (CE) of the optimal path.

            A new algorithm is reported which builds an alignment between two protein structures. The algorithm involves a combinatorial extension (CE) of an alignment path defined by aligned fragment pairs (AFPs) rather than the more conventional techniques using dynamic programming and Monte Carlo optimization. AFPs, as the name suggests, are pairs of fragments, one from each protein, which confer structure similarity. AFPs are based on local geometry, rather than global features such as orientation of secondary structures and overall topology. Combinations of AFPs that represent possible continuous alignment paths are selectively extended or discarded thereby leading to a single optimal alignment. The algorithm is fast and accurate in finding an optimal structure alignment and hence suitable for database scanning and detailed analysis of large protein families. The method has been tested and compared with results from Dali and VAST using a representative sample of similar structures. Several new structural similarities not detected by these other methods are reported. Specific one-on-one alignments and searches against all structures as found in the Protein Data Bank (PDB) can be performed via the Web at http://cl.sdsc.edu/ce.html.
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              Dali: a network tool for protein structure comparison.

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                Author and article information

                Journal
                Bioinformatics
                bioinformatics
                bioinfo
                Bioinformatics
                Oxford University Press
                1367-4803
                1367-4811
                1 October 2009
                30 July 2009
                30 July 2009
                : 25
                : 19
                : 2455-2465
                Affiliations
                Centre For Genomic Regulation (Pompeus Fabre University), Carrer del Doctor Aiguader 88, 08003 Barcelona, Spain
                Author notes
                * To whom correspondence should be addressed.

                Associate Editor: Jonathan Wren

                Article
                btp452
                10.1093/bioinformatics/btp452
                2752613
                19648142
                63ae8ab9-befc-4036-a7e9-8a1d370a01f5

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 3 April 2009
                : 24 June 2009
                : 16 July 2009
                Categories
                Reviews
                Sequence Analysis

                Bioinformatics & Computational biology
                Bioinformatics & Computational biology

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