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      A new and updated resource for codon usage tables

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          Abstract

          Background

          Due to the degeneracy of the genetic code, most amino acids can be encoded by multiple synonymous codons. Synonymous codons naturally occur with different frequencies in different organisms. The choice of codons may affect protein expression, structure, and function. Recombinant gene technologies commonly take advantage of the former effect by implementing a technique termed codon optimization, in which codons are replaced with synonymous ones in order to increase protein expression. This technique relies on the accurate knowledge of codon usage frequencies. Accurately quantifying codon usage bias for different organisms is useful not only for codon optimization, but also for evolutionary and translation studies: phylogenetic relations of organisms, and host-pathogen co-evolution relationships, may be explored through their codon usage similarities. Furthermore, codon usage has been shown to affect protein structure and function through interfering with translation kinetics, and cotranslational protein folding.

          Results

          Despite the obvious need for accurate codon usage tables, currently available resources are either limited in scope, encompassing only organisms from specific domains of life, or greatly outdated. Taking advantage of the exponential growth of GenBank and the creation of NCBI’s RefSeq database, we have developed a new database, the High-performance Integrated Virtual Environment-Codon Usage Tables (HIVE-CUTs), to present and analyse codon usage tables for every organism with publicly available sequencing data. Compared to existing databases, this new database is more comprehensive, addresses concerns that limited the accuracy of earlier databases, and provides several new functionalities, such as the ability to view and compare codon usage between individual organisms and across taxonomical clades, through graphical representation or through commonly used indices. In addition, it is being routinely updated to keep up with the continuous flow of new data in GenBank and RefSeq.

          Conclusion

          Given the impact of codon usage bias on recombinant gene technologies, this database will facilitate effective development and review of recombinant drug products and will be instrumental in a wide area of biological research. The database is available at hive.biochemistry.gwu.edu/review/codon.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12859-017-1793-7) contains supplementary material, which is available to authorized users.

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          Most cited references44

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          Principles that govern the folding of protein chains.

          C ANFINSEN (1973)
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            D³: Data-Driven Documents.

            Data-Driven Documents (D3) is a novel representation-transparent approach to visualization for the web. Rather than hide the underlying scenegraph within a toolkit-specific abstraction, D3 enables direct inspection and manipulation of a native representation: the standard document object model (DOM). With D3, designers selectively bind input data to arbitrary document elements, applying dynamic transforms to both generate and modify content. We show how representational transparency improves expressiveness and better integrates with developer tools than prior approaches, while offering comparable notational efficiency and retaining powerful declarative components. Immediate evaluation of operators further simplifies debugging and allows iterative development. Additionally, we demonstrate how D3 transforms naturally enable animation and interaction with dramatic performance improvements over intermediate representations. © 2010 IEEE
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              The 'effective number of codons' used in a gene.

              F. Wright (1990)
              A simple measure is presented that quantifies how far the codon usage of a gene departs from equal usage of synonymous codons. This measure of synonymous codon usage bias, the 'effective number of codons used in a gene', Nc, can be easily calculated from codon usage data alone, and is independent of gene length and amino acid (aa) composition. Nc can take values from 20, in the case of extreme bias where one codon is exclusively used for each aa, to 61 when the use of alternative synonymous codons is equally likely. Nc thus provides an intuitively meaningful measure of the extent of codon preference in a gene. Codon usage patterns across genes can be investigated by the Nc-plot: a plot of Nc vs. G + C content at synonymous sites. Nc-plots are produced for Homo sapiens, Saccharomyces cerevisiae, Escherichia coli, Bacillus subtilis, Dictyostelium discoideum, and Drosophila melanogaster. A FORTRAN77 program written to calculate Nc is available on request.
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                Author and article information

                Contributors
                John.Athey@fda.hhs.gov
                Aikaterini.Alexaki@fda.hhs.gov
                Ekaterina.Osipova@fda.hhs.gov
                Alexandre.Rostovtsev@fda.hhs.gov
                Luis.Santana-Quintero@fda.hhs.gov
                Upendra.Katneni@fda.hhs.gov
                Vahan.Simonyan@fda.hhs.gov
                001-240-402-8203 , Chava.Kimchi-Sarfaty@fda.hhs.gov
                Journal
                BMC Bioinformatics
                BMC Bioinformatics
                BMC Bioinformatics
                BioMed Central (London )
                1471-2105
                2 September 2017
                2 September 2017
                2017
                : 18
                : 391
                Affiliations
                [1 ]ISNI 0000 0001 2243 3366, GRID grid.417587.8, Division of Plasma Protein Therapeutics, , Office of Tissue and Advanced Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, ; Silver Spring, USA
                [2 ]ISNI 0000 0001 2243 3366, GRID grid.417587.8, High Performance Integrated Environment, , Center for Biologics Evaluation and Research, Food and Drug Administration, ; Silver Spring, USA
                Author information
                http://orcid.org/0000-0002-9355-8585
                Article
                1793
                10.1186/s12859-017-1793-7
                5581930
                28865429
                ce52721c-085a-44ec-81fb-d8e25530812c
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 19 June 2017
                : 15 August 2017
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000038, U.S. Food and Drug Administration;
                Categories
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                Custom metadata
                © The Author(s) 2017

                Bioinformatics & Computational biology
                codon usage bias,codon optimization,recombinant protein therapeutics,translational kinetics

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