{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,21]],"date-time":"2025-09-21T18:26:18Z","timestamp":1758479178889},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"published-print":{"date-parts":[[2007,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Despite a remarkable success in the computational prediction of genes in Bacteria and Archaea, a lack of comprehensive understanding of prokaryotic gene structures prevents from further elucidation of differences among genomes. It continues to be interesting to develop new <jats:italic>ab initio<\/jats:italic> algorithms which not only accurately predict genes, but also facilitate comparative studies of prokaryotic genomes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>This paper describes a new prokaryotic genefinding algorithm based on a comprehensive statistical model of protein coding Open Reading Frames (ORFs) and Translation Initiation Sites (TISs). The former is based on a linguistic \"Entropy Density Profile\" (EDP) model of coding DNA sequence and the latter comprises several relevant features related to the translation initiation. They are combined to form a so-called Multivariate Entropy Distance (MED) algorithm, MED 2.0, that incorporates several strategies in the iterative program. The iterations enable us to develop a non-supervised learning process and to obtain a set of genome-specific parameters for the gene structure, before making the prediction of genes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Results of extensive tests show that MED 2.0 achieves a competitive high performance in the gene prediction for both 5' and 3' end matches, compared to the current best prokaryotic gene finders. The advantage of the MED 2.0 is particularly evident for GC-rich genomes and archaeal genomes. Furthermore, the genome-specific parameters given by MED 2.0 match with the current understanding of prokaryotic genomes and may serve as tools for comparative genomic studies. In particular, MED 2.0 is shown to reveal divergent translation initiation mechanisms in archaeal genomes while making a more accurate prediction of TISs compared to the existing gene finders and the current GenBank annotation.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2105-8-97","type":"journal-article","created":{"date-parts":[[2007,5,2]],"date-time":"2007-05-02T15:36:18Z","timestamp":1178120178000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["MED: a new non-supervised gene prediction algorithm for bacterial and archaeal genomes"],"prefix":"10.1186","volume":"8","author":[{"given":"Huaiqiu","family":"Zhu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gang-Qing","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Fan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen-Su","family":"She","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2007,3,16]]},"reference":[{"key":"1469_CR1","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/0097-8485(93)85004-V","volume":"17","author":"M Borodovsky","year":"1993","unstructured":"Borodovsky M, Mclninch J: GENMARK: parallel gene recognition for both DNA strands. Comput Chem 1993, 17: 123\u2013133. 10.1016\/0097-8485(93)85004-V","journal-title":"Comput Chem"},{"key":"1469_CR2","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1093\/bib\/5.2.118","volume":"5","author":"RK Azad","year":"2004","unstructured":"Azad RK, Borodovsky M: Probabilistic methods of identifying genes in prokaryotic genomes: connections to the HMM theory. Brief Bioinform 2004, 5: 118\u2013130. 10.1093\/bib\/5.2.118","journal-title":"Brief Bioinform"},{"key":"1469_CR3","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1093\/nar\/26.2.544","volume":"26","author":"SL Salzberg","year":"1998","unstructured":"Salzberg SL, Delcher AL, Kasif S, White O: Microbial gene identification using interpolated Markov models. Nucleic Acids Res 1998, 26: 544\u2013548. 10.1093\/nar\/26.2.544","journal-title":"Nucleic Acids Res"},{"key":"1469_CR4","doi-asserted-by":"publisher","first-page":"4636","DOI":"10.1093\/nar\/27.23.4636","volume":"27","author":"AL Delcher","year":"1999","unstructured":"Delcher AL, Harmon D, Kasif S, White O, Salzberg SL: Improved microbial gene identification with GLIMMER. Nucleic Acids Res 1999, 27: 4636\u20134641. 10.1093\/nar\/27.23.4636","journal-title":"Nucleic Acids Res"},{"key":"1469_CR5","doi-asserted-by":"publisher","first-page":"1780","DOI":"10.1093\/nar\/gkg254","volume":"31","author":"FB Guo","year":"2003","unstructured":"Guo FB, Y OH, Zhang CT: ZCURVE: a new system for recognizing protein-coding genes in bacterial and archaeal genomes. Nucleic Acids Res 2003, 31: 1780\u20131789. 10.1093\/nar\/gkg254","journal-title":"Nucleic Acids Res"},{"key":"1469_CR6","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/S0097-8485(97)00008-9","volume":"21","author":"R Guigo","year":"1997","unstructured":"Guigo R: Computational gene identification: an open problem. Computers Chem 1997, 21: 215\u2013222. 10.1016\/S0097-8485(97)00008-9","journal-title":"Computers Chem"},{"key":"1469_CR7","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/1471-2105-3-5","volume":"3","author":"S Bocs","year":"2002","unstructured":"Bocs S, Danchin A, Medigue C: Re-annotation of genome microbial CoDing-Sequencing: finding new genes and inaccurately annotated genes. BMC Bioinformatics 2002, 3: 5. 10.1186\/1471-2105-3-5","journal-title":"BMC Bioinformatics"},{"key":"1469_CR8","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.gene.2004.10.018","volume":"346","author":"T Nishi","year":"2005","unstructured":"Nishi T, Ikemurad T, Kanaya S: GeneLook: a novel ab initio gene identification system suitable for automated annotation of prokaryotic sequences. Gene 2005, 346: 115\u2013125. 10.1016\/j.gene.2004.10.018","journal-title":"Gene"},{"key":"1469_CR9","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1038\/ng0393-266","volume":"3","author":"W Gish","year":"1993","unstructured":"Gish W, States DJ: Identification of protein coding regions by database similarity search. Nat Genet 1993, 3: 266\u2013272. 10.1038\/ng0393-266","journal-title":"Nat Genet"},{"key":"1469_CR10","doi-asserted-by":"publisher","first-page":"3389","DOI":"10.1093\/nar\/25.17.3389","volume":"25","author":"SF Altschul","year":"1997","unstructured":"Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ: Gapped BLAST and PSI-BLAST: A new generation of protein database search programs. Nucleic Acids Res 1997, 25: 3389\u20133402. 10.1093\/nar\/25.17.3389","journal-title":"Nucleic Acids Res"},{"key":"1469_CR11","doi-asserted-by":"publisher","first-page":"2941","DOI":"10.1093\/nar\/26.12.2941","volume":"26","author":"D Frishman","year":"1998","unstructured":"Frishman D, Mironov A, Mewes HW, Gelfand M: Combining diverse evidence for gene recognition in completely sequenced bacterial genomes. Nucleic Acids Res 1998, 26: 2941\u20132947. 10.1093\/nar\/26.12.2941","journal-title":"Nucleic Acids Res"},{"key":"1469_CR12","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/1471-2105-4-21","volume":"4","author":"TS Larsen","year":"2003","unstructured":"Larsen TS, Krogh A: EasyGene \u2013 a prokaryotic gene finder that ranks ORFs by statistical significance. BMC Bioinformatics 2003, 4: 21. 10.1186\/1471-2105-4-21","journal-title":"BMC Bioinformatics"},{"key":"1469_CR13","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1016\/S0168-9525(01)02348-4","volume":"17","author":"D Devos","year":"2001","unstructured":"Devos D, Valencia A: Intrinsic errors in genome annotation. Trends Genet 2001, 17: 429\u2013431. 10.1016\/S0168-9525(01)02348-4","journal-title":"Trends Genet"},{"key":"1469_CR14","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/S0168-9525(01)02372-1","volume":"17","author":"M Skovgaard","year":"2001","unstructured":"Skovgaard M, Jensen LJ, Brunak S, Ussery D, Krogh A: On the total number of genes and their length distribution in complete microbial genomes. Trends Genet 2001, 17: 425\u2013428. 10.1016\/S0168-9525(01)02372-1","journal-title":"Trends Genet"},{"key":"1469_CR15","doi-asserted-by":"publisher","first-page":"4322","DOI":"10.1093\/bioinformatics\/bti701","volume":"21","author":"P Nielsen","year":"2005","unstructured":"Nielsen P, Krogh A: Large-scale prokaryotic gene prediction and comparison to genome annotation. Bioinformatics 2005, 21: 4322\u20134329. 10.1093\/bioinformatics\/bti701","journal-title":"Bioinformatics"},{"key":"1469_CR16","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1093\/dnares\/11.6.361","volume":"11","author":"FB Guo","year":"2004","unstructured":"Guo FB, Wang J, Zhang CT: Gene recognition based on nucleotide distribution of ORFs in a hyper-thermophilic Crenarchaeon, Aeropyrum Pernix K1 . DNA Res 2004, 11: 361\u2013370. 10.1093\/dnares\/11.6.361","journal-title":"DNA Res"},{"key":"1469_CR17","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.fmrre.2004.10.002","volume":"29","author":"P Londei","year":"2005","unstructured":"Londei P: Evolution of translational initiation: new insights from the archaea. FEMS Microbiol Rev 2005, 29: 185\u2013200. 10.1016\/j.femsre.2004.10.002","journal-title":"FEMS Microbiol Rev"},{"key":"1469_CR18","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1111\/j.1462-2920.2004.00674.x","volume":"7","author":"E Torarinsson","year":"2005","unstructured":"Torarinsson E, Klenk HP, Garrett RA: Divergent transcriptional and translational signals in Archaea. Environ Microbiol 2005, 7: 47\u201354. 10.1111\/j.1462-2920.2004.00674.x","journal-title":"Environ Microbiol"},{"key":"1469_CR19","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1142\/S0219720004000624","volume":"2","author":"ZQ Ouyang","year":"2004","unstructured":"Ouyang ZQ, Zhu HQ, Wang J, She ZS: Multivariate entropy distance method for prokaryotic gene identification. J Bioinform Comput Biol 2004, 2: 353\u2013373. 10.1142\/S0219720004000624","journal-title":"J Bioinform Comput Biol"},{"key":"1469_CR20","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1016\/S0014-5793(03)00263-1","volume":"540","author":"HY Ou","year":"2003","unstructured":"Ou HY, Guo FB, Zhang CT: Analysis of nucleotide distribution in the genome of Streptomyces coelicolor A3(2) using the Z curve method. FEBS Lett 2003, 540: 188\u2013194. 10.1016\/S0014-5793(03)00263-1","journal-title":"FEBS Lett"},{"key":"1469_CR21","unstructured":"Glimmer[http:\/\/www.tigr.org\/software\/]"},{"key":"1469_CR22","doi-asserted-by":"publisher","first-page":"3308","DOI":"10.1093\/bioinformatics\/bth390","volume":"20","author":"HQ Zhu","year":"2004","unstructured":"Zhu HQ, Hu GQ, Ouyang ZQ, Wang J, She ZS: Accuracy improvement for identification of translation initiation sites in microbial genomes. Bioinformatics 2004, 20: 3308\u20133317. 10.1093\/bioinformatics\/bth390","journal-title":"Bioinformatics"},{"key":"1469_CR23","doi-asserted-by":"publisher","first-page":"2607","DOI":"10.1093\/nar\/29.12.2607","volume":"29","author":"J Besemer","year":"2001","unstructured":"Besemer J, Lomsadze A, Borodovsky M: GeneMarkS: a self-training method for prediction of gene starts in microbial genomes. Implications for finding sequence motifs in regulatory regions. Nucleic Acids Res 2001, 29: 2607\u20132618. 10.1093\/nar\/29.12.2607","journal-title":"Nucleic Acids Res"},{"key":"1469_CR24","doi-asserted-by":"publisher","first-page":"1342","DOI":"10.1073\/pnas.71.4.1342","volume":"71","author":"J Shine","year":"1974","unstructured":"Shine J, Dalgarno L: The 3'-terminal sequence of E. coli 16S ribosomal RNA: complementarity to nonsense triplets and ribosome binding sites. Proc Natl Acad Sci USA 1974, 71: 1342\u20131346. 10.1073\/pnas.71.4.1342","journal-title":"Proc Natl Acad Sci USA"},{"key":"1469_CR25","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.gene.2004.02.022","volume":"332","author":"A Fuglsang","year":"2004","unstructured":"Fuglsang A: Compositional nonrandomness upstream of start codons in archaebacteria. Gene 2004, 332: 89\u201395. 10.1016\/j.gene.2004.02.022","journal-title":"Gene"},{"key":"1469_CR26","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1007\/s007920070032","volume":"4","author":"N Tolstrup","year":"2000","unstructured":"Tolstrup N, Sensen CW, Garrett RA, Clausen IG: Two different and highly organized mechanisms of translation initiation in the archaeon Sulfolobus solfataricus. Extremophiles 2000, 4: 175\u2013179. 10.1007\/s007920070032","journal-title":"Extremophiles"},{"key":"1469_CR27","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1093\/nar\/28.1.60","volume":"28","author":"KE Rudd","year":"2000","unstructured":"Rudd KE: EcoGene: a genome sequence database for Escherichia coli K-12 . Nucleic Acids Res 2000, 28: 60\u201364. 10.1093\/nar\/28.1.60","journal-title":"Nucleic Acids Res"},{"key":"1469_CR28","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.1002\/elps.1150180807","volume":"18","author":"AJ Link","year":"1997","unstructured":"Link AJ, Robison K, Church GM: Comparing the predicted and observed properties of proteins encoded in the genome of Escherichia coli K-12 . Electrophoresis 1997, 18: 1259\u20131313. 10.1002\/elps.1150180807","journal-title":"Electrophoresis"},{"key":"1469_CR29","unstructured":"MED[http:\/\/ctb.pku.edu.cn\/main\/SheGroup\/MED2.htm]"},{"key":"1469_CR30","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1093\/bioinformatics\/17.12.1123","volume":"17","author":"BE Suzek","year":"2001","unstructured":"Suzek BE, Ermolaeva MD, Schreiber M, Salzberg SL: A probabilistic method for identifying start codons in bacterial genomes. Bioinformatics 2001, 17: 1123\u20131130. 10.1093\/bioinformatics\/17.12.1123","journal-title":"Bioinformatics"},{"key":"1469_CR31","unstructured":"RBSfinder[ftp:\/\/ftp.tigr.org\/pub\/software\/RBSfinder\/]"},{"key":"1469_CR32","unstructured":"ZCURVE[http:\/\/tubic.tju.edu.cn\/Zcurve_B]"},{"key":"1469_CR33","unstructured":"GeneMarkS[http:\/\/exon.gatech.edu\/GeneMark\/genemarks.cgi]"},{"key":"1469_CR34","unstructured":"EasyGene[http:\/\/www.cbs.dtu.dk\/services\/EasyGene\/]"},{"key":"1469_CR35","unstructured":"The NCBI Taxonomy Homepage[http:\/\/www.ncbi.nlm.nih.gov\/Taxonomy\/taxonomyhome.html\/]"},{"key":"1469_CR36","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1038\/nrmicro1204","volume":"3","author":"JP Gogarten","year":"2005","unstructured":"Gogarten JP, Townsend JP: Horizontal gene transfer: genome innovation and evolution. Nat Rev Microbiol 2005, 3: 679\u2013687. 10.1038\/nrmicro1204","journal-title":"Nat Rev Microbiol"},{"key":"1469_CR37","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1038\/20601","volume":"399","author":"KE Nelson","year":"1999","unstructured":"Nelson KE, Clayton RA, Gill SR, Gwinn ML, Dodson RJ, Haft DH, Hickey EK, Peterson JD, Nelson WC, Ketchum KA, McDonald L, Utterback TR, Malek JA, Linher KD, Garrett MM, Stewart AM, Cotton MD, Pratt MS, Phillips CA, Richardson D, Heidelberg J, Sutton GG, Fleischmann RD, Eisen JA, White O, Salzberg SL, Smith HO, Venter JC, Fraser CM: Evidence for lateral gene transfer between archaea and bacteria from genome sequence of Thermotoga maritima. Nature 1999, 399: 323\u2013329. 10.1038\/20601","journal-title":"Nature"},{"key":"1469_CR38","first-page":"583","volume":"13","author":"J Gorodkin","year":"1997","unstructured":"Gorodkin J, Heyer LJ, Brunak S, Stormo GD: Displaying the information contents of structural RNA alignments: the structure logos. Comput Appli Biosci 1997, 13: 583\u2013586.","journal-title":"Comput Appli Biosci"}],"container-title":["BMC Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2105-8-97.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T01:53:37Z","timestamp":1630461217000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/1471-2105-8-97"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,3,16]]},"references-count":38,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2007,12]]}},"alternative-id":["1469"],"URL":"https:\/\/doi.org\/10.1186\/1471-2105-8-97","relation":{},"ISSN":["1471-2105"],"issn-type":[{"value":"1471-2105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,3,16]]},"assertion":[{"value":"30 September 2006","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 March 2007","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 March 2007","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"97"}}