{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:51:12Z","timestamp":1782953472746,"version":"3.54.5"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T00:00:00Z","timestamp":1727395200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T00:00:00Z","timestamp":1727395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Pearl Plan (Pearl Elite Talent Award) of Pudong New Area of Shanghai Municipality"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>The study of codon usage bias is important for understanding gene expression, evolution and gene design, providing critical insights into the molecular processes that govern the function and regulation of genes. Codon Usage Bias (CUB) indices are valuable metrics for understanding codon usage patterns across different organisms without extensive experiments. Considering that there is no one-fits-all index for all species, a comprehensive platform supporting the calculation and analysis of multiple CUB indices for codon optimization is greatly needed.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Here, we release GenRCA, an updated version of our previous Rare Codon Analysis Tool, as a free and user-friendly website for all-inclusive evaluation of codon usage preferences of coding sequences. In this study, we manually reviewed and implemented up to 31 codon preference indices, with 65 expression host organisms covered and batch processing of multiple gene sequences supported, aiming to improve the user experience and provide more comprehensive and efficient analysis.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our website fills a gap in the availability of comprehensive tools for species-specific CUB calculations, enabling researchers to thoroughly assess the protein expression level based on a comprehensive list of 31 indices and further guide the codon optimization.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12859-024-05934-z","type":"journal-article","created":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T12:02:07Z","timestamp":1727438527000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["GenRCA: a user-friendly rare codon analysis tool for comprehensive evaluation of codon usage preferences based on coding sequences in genomes"],"prefix":"10.1186","volume":"25","author":[{"given":"Kunjie","family":"Fan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,9,27]]},"reference":[{"key":"5934_CR1","doi-asserted-by":"publisher","first-page":"2646","DOI":"10.1016\/j.csbj.2021.04.042","volume":"19","author":"S Bahiri-Elitzur","year":"2021","unstructured":"Bahiri-Elitzur S, Tuller T. Codon-based indices for modeling gene expression and transcript evolution. Comput Struct Biotechnol J. 2021;19:2646\u201363.","journal-title":"Comput Struct Biotechnol J"},{"key":"5934_CR2","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1146\/annurev.genet.42.110807.091442","volume":"42","author":"R Hershberg","year":"2008","unstructured":"Hershberg R, Petrov DA. Selection on codon bias. Annu Rev Genet. 2008;42:287\u201399.","journal-title":"Annu Rev Genet"},{"key":"5934_CR3","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1007\/s11033-021-06749-4","volume":"49","author":"ST Parvathy","year":"2022","unstructured":"Parvathy ST, Udayasuriyan V, Bhadana V. Codon usage bias. Mol Biol Rep. 2022;49:539\u201365.","journal-title":"Mol Biol Rep"},{"key":"5934_CR4","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1186\/s12964-020-00642-6","volume":"18","author":"Y Liu","year":"2020","unstructured":"Liu Y. A code within the genetic code: codon usage regulates co-translational protein folding. Cell Commun Signal. 2020;18:145.","journal-title":"Cell Commun Signal"},{"key":"5934_CR5","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1186\/s12859-017-1793-7","volume":"18","author":"J Athey","year":"2017","unstructured":"Athey J, et al. A new and updated resource for codon usage tables. BMC Bioinf. 2017;18:391.","journal-title":"BMC Bioinf"},{"key":"5934_CR6","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.molcel.2015.05.035","volume":"59","author":"TEF Quax","year":"2015","unstructured":"Quax TEF, Claassens NJ, S\u00f6ll D, van der Oost J. Codon bias as a means to fine-tune gene expression. Mol Cell. 2015;59:149\u201361.","journal-title":"Mol Cell"},{"key":"5934_CR7","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1007\/BF02099948","volume":"24","author":"PM Sharp","year":"1986","unstructured":"Sharp PM, Li WH. An evolutionary perspective on synonymous codon usage in unicellular organisms. J Mol Evol. 1986;24:28\u201338.","journal-title":"J Mol Evol"},{"key":"5934_CR8","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/0378-1119(90)90491-9","volume":"87","author":"F Wright","year":"1990","unstructured":"Wright F. The \u2018effective number of codons\u2019 used in a gene. Gene. 1990;87:23\u20139.","journal-title":"Gene"},{"key":"5934_CR9","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1111\/gtc.12474","volume":"22","author":"SS Satapathy","year":"2017","unstructured":"Satapathy SS, Sahoo AK, Ray SK, Ghosh TC. Codon degeneracy and amino acid abundance influence the measures of codon usage bias: improved Nc ( N\u0302 c ) and ENCprime ( N\u0302 \u2032 c ) measures. Genes Cells. 2017;22:277\u201383.","journal-title":"Genes Cells"},{"key":"5934_CR10","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1093\/dnares\/dsn029","volume":"16","author":"U Roymondal","year":"2009","unstructured":"Roymondal U, Das S, Sahoo S. Predicting gene expression level from relative codon usage bias: an application to Escherichia coli genome. DNA Res. 2009;16:13\u201330.","journal-title":"DNA Res"},{"key":"5934_CR11","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1093\/dnares\/dsu017","volume":"21","author":"R Sabi","year":"2014","unstructured":"Sabi R, Tuller T. Modelling the efficiency of codon\u2013tRNA interactions based on codon usage bias. DNA Res. 2014;21:511\u201326.","journal-title":"DNA Res"},{"key":"5934_CR12","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/1471-2105-13-43","volume":"13","author":"Z Zhang","year":"2012","unstructured":"Zhang Z, et al. Codon Deviation Coefficient: a novel measure for estimating codon usage bias and its statistical significance. BMC Bioinf. 2012;13:43.","journal-title":"BMC Bioinf"},{"key":"5934_CR13","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1186\/1471-2105-6-182","volume":"6","author":"F Supek","year":"2005","unstructured":"Supek F, Vlahovi\u010dek K. Comparison of codon usage measures and their applicability in prediction of microbial gene expressivity. BMC Bioinf. 2005;6:182.","journal-title":"BMC Bioinf"},{"key":"5934_CR14","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/0378-1119(94)90521-5","volume":"139","author":"MA Freire-Picos","year":"1994","unstructured":"Freire-Picos MA, et al. Codon usage in Kluyveromyces lactis and in yeast cytochrome c-encoding genes. Gene. 1994;139:43\u20139.","journal-title":"Gene"},{"key":"5934_CR15","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/1471-2148-4-19","volume":"4","author":"X-F Wan","year":"2004","unstructured":"Wan X-F, Xu D, Kleinhofs A, Zhou J. Quantitative relationship between synonymous codon usage bias and GC composition across unicellular genomes. BMC Evol Biol. 2004;4:19.","journal-title":"BMC Evol Biol"},{"key":"5934_CR16","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1080\/03081070500502967","volume":"35","author":"X-F Wan","year":"2006","unstructured":"Wan X-F, Zhou J, Xu D. CodonO: a new informatics method for measuring synonymous codon usage bias within and across genomes. Int J Gen Syst. 2006;35:109\u201325.","journal-title":"Int J Gen Syst"},{"key":"5934_CR17","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.gene.2004.03.001","volume":"335","author":"H Suzuki","year":"2004","unstructured":"Suzuki H, Saito R, Tomita M. The \u2018weighted sum of relative entropy\u2019: a new index for synonymous codon usage bias. Gene. 2004;335:19\u201323.","journal-title":"Gene"},{"key":"5934_CR18","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1093\/nar\/12.1Part2.539","volume":"12","author":"M Gribskov","year":"1984","unstructured":"Gribskov M, Devereux J, Burgess RR. The codon preference plot: graphic analysis of protein coding sequences and prediction of gene expression. Nucleic Acids Res. 1984;12:539\u201349.","journal-title":"Nucleic Acids Res"},{"key":"5934_CR19","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.1093\/genetics\/159.3.1191","volume":"159","author":"AO Urrutia","year":"2001","unstructured":"Urrutia AO, Hurst LD. Codon usage bias covaries with expression breadth and the rate of synonymous evolution in humans, but this is not evidence for selection. Genetics. 2001;159:1191\u20139.","journal-title":"Genetics"},{"key":"5934_CR20","doi-asserted-by":"publisher","first-page":"1281","DOI":"10.1093\/nar\/15.3.1281","volume":"15","author":"PM Sharp","year":"1987","unstructured":"Sharp PM, Li WH. The codon adaptation index-a measure of directional synonymous codon usage bias, and its potential applications. Nucleic Acids Res. 1987;15:1281\u201395.","journal-title":"Nucleic Acids Res"},{"key":"5934_CR21","doi-asserted-by":"crossref","unstructured":"Ikemura T. Correlation between the abundance of Escherichia coli transfer RNAs and the occurrence of the respective codons in its protein genes: a proposal for a synonymous codon choice that is optimal for the E. coli translational system. J. Mol. Biol. 1981;151, 389\u2013409.","DOI":"10.1016\/0022-2836(81)90003-6"},{"key":"5934_CR22","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1016\/0022-2836(82)90250-9","volume":"158","author":"T Ikemura","year":"1982","unstructured":"Ikemura T. Correlation between the abundance of yeast transfer RNAs and the occurrence of the respective codons in protein genes. J Mol Biol. 1982;158:573\u201397.","journal-title":"J Mol Biol"},{"key":"5934_CR23","doi-asserted-by":"publisher","first-page":"3523","DOI":"10.1093\/gbe\/evz262","volume":"11","author":"J Bourret","year":"2019","unstructured":"Bourret J, Alizon S, Bravo IG. COUSIN (COdon usage similarity INdex): a normalized measure of codon usage preferences. Genome Biol Evol. 2019;11:3523\u20138.","journal-title":"Genome Biol Evol"},{"key":"5934_CR24","doi-asserted-by":"publisher","first-page":"3026","DOI":"10.1016\/S0021-9258(19)81068-2","volume":"257","author":"JL Bennetzen","year":"1982","unstructured":"Bennetzen JL, Hall BD. Codon selection in yeast. J Biol Chem. 1982;257:3026\u201331.","journal-title":"J Biol Chem"},{"key":"5934_CR25","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1186\/1471-2105-10-167","volume":"10","author":"H Suzuki","year":"2009","unstructured":"Suzuki H, Saito R, Tomita M. Measure of synonymous codon usage diversity among genes in bacteria. BMC Bioinf. 2009;10:167.","journal-title":"BMC Bioinf"},{"key":"5934_CR26","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1093\/dnares\/dsq012","volume":"17","author":"JM Fox","year":"2010","unstructured":"Fox JM, Erill I. Relative codon adaptation: a generic codon bias index for prediction of gene expression. DNA Res. 2010;17:185\u201396.","journal-title":"DNA Res"},{"key":"5934_CR27","doi-asserted-by":"publisher","first-page":"5876","DOI":"10.1038\/ncomms6876","volume":"5","author":"A Diament","year":"2014","unstructured":"Diament A, Pinter RY, Tuller T. Three-dimensional eukaryotic genomic organization is strongly correlated with codon usage expression and function. Nat Commun. 2014;5:5876.","journal-title":"Nat Commun"},{"key":"5934_CR28","doi-asserted-by":"publisher","first-page":"1341","DOI":"10.1046\/j.1365-2958.1998.01008.x","volume":"29","author":"S Karlin","year":"1998","unstructured":"Karlin S, Mr\u00e1zek J, Campbell AM. Codon usages in different gene classes of the Escherichia coli genome. Mol Microbiol. 1998;29:1341\u201355.","journal-title":"Mol Microbiol"},{"key":"5934_CR29","doi-asserted-by":"crossref","unstructured":"Reis Md. Solving the riddle of codon usage preferences: a test for translational selection. Nucleic Acids Res. 2004;32, 5036\u20135044.","DOI":"10.1093\/nar\/gkh834"},{"key":"5934_CR30","doi-asserted-by":"publisher","first-page":"1218518","DOI":"10.3389\/fmolb.2023.1218518","volume":"10","author":"AM Anwar","year":"2023","unstructured":"Anwar AM, et al. gtAI: an improved species-specific tRNA adaptation index using the genetic algorithm. Front Mol Biosci. 2023;10:1218518.","journal-title":"Front Mol Biosci"},{"key":"5934_CR31","doi-asserted-by":"publisher","first-page":"7055","DOI":"10.1093\/nar\/10.22.7055","volume":"10","author":"M Gouy","year":"1982","unstructured":"Gouy M, Gautier C. Codon usage in bacteria: correlation with gene expressivity. Nucleic Acids Res. 1982;10:7055\u201374.","journal-title":"Nucleic Acids Res"},{"key":"5934_CR32","doi-asserted-by":"publisher","first-page":"2437","DOI":"10.1093\/nar\/22.13.2437","volume":"22","author":"M Stenico","year":"1994","unstructured":"Stenico M, Lloyd AT, Sharp PM. Codon usage in Caenorhabditis elegans: delineation of translational selection and mutational biases. Nucleic Acids Res. 1994;22:2437\u201346.","journal-title":"Nucleic Acids Res"},{"key":"5934_CR33","doi-asserted-by":"publisher","first-page":"2434","DOI":"10.1016\/j.jmb.2019.04.021","volume":"431","author":"A Alexaki","year":"2019","unstructured":"Alexaki A, et al. Codon and codon-pair usage tables (CoCoPUTs): facilitating genetic variation analyses and recombinant gene design. J Mol Biol. 2019;431:2434\u201341.","journal-title":"J Mol Biol"},{"key":"5934_CR34","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.celrep.2015.12.011","volume":"14","author":"D Kunec","year":"2016","unstructured":"Kunec D, Osterrieder N. Codon pair bias is a direct consequence of dinucleotide bias. Cell Rep. 2016;14:55\u201367.","journal-title":"Cell Rep"},{"key":"5934_CR35","doi-asserted-by":"publisher","first-page":"1784","DOI":"10.1126\/science.1155761","volume":"320","author":"JR Coleman","year":"2008","unstructured":"Coleman JR, et al. Virus attenuation by genome-scale changes in codon pair bias. Science. 2008;320:1784\u20137.","journal-title":"Science"},{"key":"5934_CR36","doi-asserted-by":"crossref","unstructured":"Plotkin JB, Dushoff J, Fraser HB. Detecting selection using a single genome sequence of M. tuberculosis and P. falciparum. Nature 428, 942\u2013945 (2004).","DOI":"10.1038\/nature02458"},{"key":"5934_CR37","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1038\/nature02046","volume":"425","author":"S Ghaemmaghami","year":"2003","unstructured":"Ghaemmaghami S, et al. Global analysis of protein expression in yeast. Nature. 2003;425:737\u201341.","journal-title":"Nature"},{"key":"5934_CR38","doi-asserted-by":"publisher","first-page":"5265","DOI":"10.1021\/pr300476w","volume":"11","author":"D Baycin-Hizal","year":"2012","unstructured":"Baycin-Hizal D, et al. Proteomic analysis of Chinese hamster ovary cells. J Proteome Res. 2012;11:5265\u201376.","journal-title":"J Proteome Res"},{"key":"5934_CR39","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1038\/nbt1270","volume":"25","author":"P Lu","year":"2007","unstructured":"Lu P, Vogel C, Wang R, Yao X, Marcotte EM. Absolute protein expression profiling estimates the relative contributions of transcriptional and translational regulation. Nat Biotechnol. 2007;25:117\u201324.","journal-title":"Nat Biotechnol"},{"key":"5934_CR40","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/nature10098","volume":"473","author":"B Schwanh\u00e4usser","year":"2011","unstructured":"Schwanh\u00e4usser B, et al. Global quantification of mammalian gene expression control. Nature. 2011;473:337\u201342.","journal-title":"Nature"},{"key":"5934_CR41","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007002","volume":"4","author":"M Welch","year":"2009","unstructured":"Welch M, et al. Design parameters to control synthetic gene expression in Escherichia coli. PLoS ONE. 2009;4: e7002.","journal-title":"PLoS ONE"},{"key":"5934_CR42","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1126\/science.1170160","volume":"324","author":"G Kudla","year":"2009","unstructured":"Kudla G, Murray AW, Tollervey D, Plotkin JB. Coding-sequence determinants of gene expression in Escherichia coli. Science. 2009;324:255\u20138.","journal-title":"Science"},{"key":"5934_CR43","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1002\/yea.1150","volume":"21","author":"M Friberg","year":"2004","unstructured":"Friberg M, von Rohr P, Gonnet G. Limitations of codon adaptation index and other coding DNA-based features for prediction of protein expression inSaccharomyces cerevisiae. Yeast. 2004;21:1083\u201393.","journal-title":"Yeast"}],"container-title":["BMC Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-024-05934-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12859-024-05934-z\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-024-05934-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T12:02:54Z","timestamp":1727438574000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/s12859-024-05934-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,27]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["5934"],"URL":"https:\/\/doi.org\/10.1186\/s12859-024-05934-z","relation":{},"ISSN":["1471-2105"],"issn-type":[{"value":"1471-2105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,27]]},"assertion":[{"value":"20 December 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 September 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 September 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they are all employees of GenScript Biotech Corporation, or GenScript (Shanghai) Biotech Co., Ltd, which is a wholly-owned subsidiary of GenScript Biotech Corporation. The company has no financial or personal interests that could potentially influence the research findings or the objectivity of the authors.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"309"}}