{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T23:07:10Z","timestamp":1780960030066,"version":"3.54.1"},"reference-count":18,"publisher":"Oxford University Press (OUP)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Overlapping gene coding sequences (CDSs) are particularly common in viruses but also occur in more complex genomes. Detecting such genes with conventional gene-finding algorithms can be difficult for several reasons. If an overlapping CDS is on the same read-strand as a known CDS, then there may not be a distinct promoter or mRNA. Furthermore, the constraints imposed by double-coding can result in atypical codon biases. However, these same constraints lead to particular mutation patterns that may be detectable in sequence alignments.<\/jats:p>\n               <jats:p>Results: In this paper, we investigate several statistics for detecting double-coding sequences with pairwise alignments\u2014including a new maximum-likelihood method. We also develop a model for double-coding sequence evolution. Using simulated sequences generated with the model, we characterize the distribution of each statistic as a function of sequence composition, length, divergence time and double-coding frame. Using these results, we develop several algorithms for detecting overlapping CDSs.<\/jats:p>\n               <jats:p>The algorithms were tested on known overlapping CDSs and other overlapping open reading frames (ORFs) in the hepatitis B virus (HBV), Escherichia coli and Salmonella typhimurium genomes. The algorithms should prove useful for detecting novel overlapping genes\u2014especially short coding ORFs in viruses.<\/jats:p>\n               <jats:p>Availability: Programs may be obtained from the authors.<\/jats:p>\n               <jats:p>Contact: \u00a0chris.brown@otago.ac.nz<\/jats:p>\n               <jats:p>Supplementary information: \u00a0http:\/\/biochem.otago.ac.nz\/double.html<\/jats:p>","DOI":"10.1093\/bioinformatics\/bti007","type":"journal-article","created":{"date-parts":[[2004,9,7]],"date-time":"2004-09-07T07:33:02Z","timestamp":1094542382000},"page":"282-292","source":"Crossref","is-referenced-by-count":36,"title":["Detecting overlapping coding sequences with pairwise alignments"],"prefix":"10.1093","volume":"21","author":[{"given":"Andrew E.","family":"Firth","sequence":"first","affiliation":[{"name":"Department of Biochemistry, University of Otago P.O. Box 56, Dunedin, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris M.","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Otago P.O. Box 56, Dunedin, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2004,9,3]]},"reference":[{"key":"2023051305564030600_B1","doi-asserted-by":"crossref","unstructured":"Bilsel, P.A., Rowe, J.E., Fitch, W.M., Nichol, S.T. 1990Phosphoprotein and nucleocapsid protein evolution of vesicular stomatitis virus New Jersey. J.Virol.642498\u20132504","DOI":"10.1128\/jvi.64.6.2498-2504.1990"},{"key":"2023051305564030600_B2","doi-asserted-by":"crossref","unstructured":"Farabaugh, P.J. 1996Programmed translational frameshifting. Annu. Rev. Genet.30507\u2013528","DOI":"10.1146\/annurev.genet.30.1.507"},{"key":"2023051305564030600_B3","doi-asserted-by":"crossref","unstructured":"Fukuda, Y., Nakayama, Y., Tomita, M. 2003On dynamics of overlapping genes in bacterial genomes. Gene323181\u2013187","DOI":"10.1016\/j.gene.2003.09.021"},{"key":"2023051305564030600_B4","unstructured":"Goldman, N. and Yang, Z. 1994A codon-based model of nucleotide substitution for protein-coding DNA sequences. Mol. Biol. Evol.11725\u2013736"},{"key":"2023051305564030600_B5","doi-asserted-by":"crossref","unstructured":"Henikoff, S. and Henikoff, J.G. 1992Amino acid substitution matrices from protein blocks. Proc. Natl Acad. Sci. USA8910915\u201310919","DOI":"10.1073\/pnas.89.22.10915"},{"key":"2023051305564030600_B6","doi-asserted-by":"crossref","unstructured":"Higgins, D., Thompson, J., Gibson, T. 1994CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res.224673\u20134680","DOI":"10.1093\/nar\/22.22.4673"},{"key":"2023051305564030600_B7","doi-asserted-by":"crossref","unstructured":"Huy, T.T., Ushijima, H., Quang, V.X., Win, K.M., Luengrojanakul, P., Kikuchi, K., Sata, T., Abe, K. 2004Genotype C of hepatitis B virus can be classified into at least two subgroups. J. Gen. Virol.85283\u2013292","DOI":"10.1099\/vir.0.19633-0"},{"key":"2023051305564030600_B8","doi-asserted-by":"crossref","unstructured":"Kimura, M. 1980A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences. J. Mol. Evol.16111\u2013120","DOI":"10.1007\/BF01731581"},{"key":"2023051305564030600_B9","doi-asserted-by":"crossref","unstructured":"Mizokami, M., Orito, E., Ohba, K., Ikeo, K., Lau, J.Y., Gojobori, T. 1997Constrained evolution with respect to gene overlap of hepatitis B virus. J. Mol. Evol.44S83\u2013S90","DOI":"10.1007\/PL00000061"},{"key":"2023051305564030600_B10","unstructured":"Normark, S., Bergstrom, S., Edlund, T., Grundstrom, T., Jaurin, B., Lindberg, F.P., Olsson, O. 1983Overlapping genes. Ann. Rev. Genet.17499\u2013525"},{"key":"2023051305564030600_B11","doi-asserted-by":"crossref","unstructured":"Pavesi, A. 2000Detection of signature sequences in overlapping genes and prediction of a novel overlapping gene in hepatitis G virus. J. Mol. Evol.50284\u2013295","DOI":"10.1007\/s002399910033"},{"key":"2023051305564030600_B12","doi-asserted-by":"crossref","unstructured":"Pavesi, A., Iaco, B., Granero, M.I., Porati, A. 1997On the informational content of overlapping genes in prokaryotic and eukaryotic viruses. J. Mol. Evol.44625\u2013631","DOI":"10.1007\/PL00006185"},{"key":"2023051305564030600_B13","doi-asserted-by":"crossref","unstructured":"Poulin, F., Brueschke, A., Sonenberg, N. 2003Gene fusion and overlapping reading frames in the mammalian genes for 4E-BP3 and MASK. J. Biol. Chem.27852290\u201352297","DOI":"10.1074\/jbc.M310761200"},{"key":"2023051305564030600_B14","doi-asserted-by":"crossref","unstructured":"Rice, P., Longden, I., Bleasby, A. 2000EMBOSS: the European Molecular Biology Open Software Suite. Trends Genet.16276\u2013277","DOI":"10.1016\/S0168-9525(00)02024-2"},{"key":"2023051305564030600_B15","doi-asserted-by":"crossref","unstructured":"Rogozin, I.B., Spiridonov, A.N., Sorokin, A.V., Wolf, Y.I., Jordan, I.K., Tatusov, R.L., Koonin, E.V. 2002Purifying and directional selection in overlapping prokaryotic genes. Trends Genet.18228\u2013232","DOI":"10.1016\/S0168-9525(02)02649-5"},{"key":"2023051305564030600_B16","doi-asserted-by":"crossref","unstructured":"Sharpless, N.E. and DePinho, R.A. 1999The INK4A\/ARF locus and its two gene products. Curr. Opin. Genet. Dev.922\u201330","DOI":"10.1016\/S0959-437X(99)80004-5"},{"key":"2023051305564030600_B17","unstructured":"Snyder, M. and Gerstein, M. 2003Defining genes in the genomics era. Science300258\u2013260"},{"key":"2023051305564030600_B18","doi-asserted-by":"crossref","unstructured":"Stormo, G.D. 2000Gene-finding approaches for eukaryotes. Genome Res.10394\u2013397","DOI":"10.1101\/gr.10.4.394"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/21\/3\/282\/50305699\/bioinformatics_21_3_282.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/21\/3\/282\/50305699\/bioinformatics_21_3_282.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,13]],"date-time":"2023-05-13T05:56:58Z","timestamp":1683957418000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/21\/3\/282\/237775"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,9,3]]},"references-count":18,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2005,2,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/bti007","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2005,2,1]]},"published":{"date-parts":[[2004,9,3]]}}}