{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T22:12:47Z","timestamp":1757542367711},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2016,10,2]],"date-time":"2016-10-02T00:00:00Z","timestamp":1475366400000},"content-version":"vor","delay-in-days":2132,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/2.0\/uk\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: The task of reconstructing a genomic sequence from a particular species is gaining more and more importance in the light of the rapid development of high-throughput sequencing technologies and their limitations. Applications include not only compensation for missing data in unsequenced genomic regions and the design of oligonucleotide primers for target genes in species with lacking sequence information but also the preparation of customized queries for homology searches.<\/jats:p>\n               <jats:p>Results: We introduce the maxAlike algorithm, which reconstructs a genomic sequence for a specific taxon based on sequence homologs in other species. The input is a multiple sequence alignment and a phylogenetic tree that also contains the target species. For this target species, the algorithm computes nucleotide probabilities at each sequence position. Consensus sequences are then reconstructed based on a certain confidence level. For 37 out of 44 target species in a test dataset, we obtain a significant increase of the reconstruction accuracy compared to both the consensus sequence from the alignment and the sequence of the nearest phylogenetic neighbor. When considering only nucleotides above a confidence limit, maxAlike is significantly better (up to 10%) in all 44 species. The improved sequence reconstruction also leads to an increase of the quality of PCR primer design for yet unsequenced genes: the differences between the expected Tm and real Tm of the primer-template duplex can be reduced by ~26% compared with other reconstruction approaches. We also show that the prediction accuracy is robust to common distortions of the input trees. The prediction accuracy drops by only 1% on average across all species for 77% of trees derived from random genomic loci in a test dataset.<\/jats:p>\n               <jats:p>Availability: \u00a0maxAlike is available for download and web server at: http:\/\/rth.dk\/resources\/maxAlike.<\/jats:p>\n               <jats:p>Contact: \u00a0gorodkin@rth.dk<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btq651","type":"journal-article","created":{"date-parts":[[2010,12,2]],"date-time":"2010-12-02T02:42:32Z","timestamp":1291257752000},"page":"317-325","source":"Crossref","is-referenced-by-count":10,"title":["maxAlike: maximum likelihood-based sequence reconstruction with application to improved primer design for unknown sequences"],"prefix":"10.1093","volume":"27","author":[{"given":"Peter","family":"Menzel","sequence":"first","affiliation":[{"name":"1 Center for non-coding RNA in Technology and Health, 2IBHV, University of Copenhagen, Gr\u00f8nneg\u00e5rdsvej 3, DK-1870 Frederiksberg, Denmark, 3Bioinformatics Group, Department of Computer Science, and Interdisciplinary Center for Bioinformatics, University of Leipzig, H\u00e4rtelstra\u00dfe 16-18, D-04107 Leipzig, 4Max Planck Institute for Mathematics in the Sciences, Inselstra\u00dfe 22, 5Fraunhofer Institut f\u00fcr Zelltherapie und Immunologie, Perlickstra\u00dfe 1, D-04103 Leipzig, Germany, 6Institute for Theoretical Chemistry, University of Vienna, W\u00e4hringerstra\u00dfe 17, A-1090 Vienna, Austria and 7The Santa Fe Institute, 1399 Hyde Park Road, Santa Fe, NM, USA"},{"name":"1 Center for non-coding RNA in Technology and Health, 2IBHV, University of Copenhagen, Gr\u00f8nneg\u00e5rdsvej 3, DK-1870 Frederiksberg, Denmark, 3Bioinformatics Group, Department of Computer Science, and Interdisciplinary Center for Bioinformatics, University of Leipzig, H\u00e4rtelstra\u00dfe 16-18, D-04107 Leipzig, 4Max Planck Institute for Mathematics in the Sciences, Inselstra\u00dfe 22, 5Fraunhofer Institut f\u00fcr Zelltherapie und Immunologie, Perlickstra\u00dfe 1, D-04103 Leipzig, Germany, 6Institute for Theoretical Chemistry, University of Vienna, W\u00e4hringerstra\u00dfe 17, A-1090 Vienna, Austria and 7The Santa Fe Institute, 1399 Hyde Park Road, Santa Fe, NM, USA"},{"name":"1 Center for non-coding RNA in Technology and Health, 2IBHV, University of Copenhagen, Gr\u00f8nneg\u00e5rdsvej 3, DK-1870 Frederiksberg, Denmark, 3Bioinformatics Group, Department of Computer Science, and Interdisciplinary Center for Bioinformatics, University of Leipzig, H\u00e4rtelstra\u00dfe 16-18, D-04107 Leipzig, 4Max Planck Institute for Mathematics in the Sciences, Inselstra\u00dfe 22, 5Fraunhofer Institut f\u00fcr Zelltherapie und Immunologie, Perlickstra\u00dfe 1, D-04103 Leipzig, Germany, 6Institute for Theoretical Chemistry, University of Vienna, W\u00e4hringerstra\u00dfe 17, A-1090 Vienna, Austria and 7The Santa Fe Institute, 1399 Hyde Park Road, Santa Fe, NM, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter F.","family":"Stadler","sequence":"additional","affiliation":[{"name":"1 Center for non-coding RNA in Technology and Health, 2IBHV, University of Copenhagen, Gr\u00f8nneg\u00e5rdsvej 3, DK-1870 Frederiksberg, Denmark, 3Bioinformatics Group, Department of Computer Science, and Interdisciplinary Center for Bioinformatics, University of Leipzig, H\u00e4rtelstra\u00dfe 16-18, D-04107 Leipzig, 4Max Planck Institute for Mathematics in the Sciences, Inselstra\u00dfe 22, 5Fraunhofer Institut f\u00fcr Zelltherapie und Immunologie, Perlickstra\u00dfe 1, D-04103 Leipzig, Germany, 6Institute for Theoretical Chemistry, University of Vienna, W\u00e4hringerstra\u00dfe 17, A-1090 Vienna, Austria and 7The Santa Fe Institute, 1399 Hyde Park Road, Santa Fe, NM, USA"},{"name":"1 Center for non-coding RNA in Technology and Health, 2IBHV, University of Copenhagen, Gr\u00f8nneg\u00e5rdsvej 3, DK-1870 Frederiksberg, Denmark, 3Bioinformatics Group, Department of Computer Science, and Interdisciplinary Center for Bioinformatics, University of Leipzig, H\u00e4rtelstra\u00dfe 16-18, D-04107 Leipzig, 4Max Planck Institute for Mathematics in the Sciences, Inselstra\u00dfe 22, 5Fraunhofer Institut f\u00fcr Zelltherapie und Immunologie, Perlickstra\u00dfe 1, D-04103 Leipzig, Germany, 6Institute for Theoretical Chemistry, University of Vienna, W\u00e4hringerstra\u00dfe 17, A-1090 Vienna, Austria and 7The Santa Fe Institute, 1399 Hyde Park Road, Santa Fe, NM, USA"},{"name":"1 Center for non-coding RNA in Technology and Health, 2IBHV, University of Copenhagen, Gr\u00f8nneg\u00e5rdsvej 3, DK-1870 Frederiksberg, Denmark, 3Bioinformatics Group, Department of Computer Science, and Interdisciplinary Center for Bioinformatics, University of Leipzig, H\u00e4rtelstra\u00dfe 16-18, D-04107 Leipzig, 4Max Planck Institute for Mathematics in the Sciences, Inselstra\u00dfe 22, 5Fraunhofer Institut f\u00fcr Zelltherapie und Immunologie, Perlickstra\u00dfe 1, D-04103 Leipzig, Germany, 6Institute for Theoretical Chemistry, University of Vienna, W\u00e4hringerstra\u00dfe 17, A-1090 Vienna, Austria and 7The Santa Fe Institute, 1399 Hyde Park Road, Santa Fe, NM, USA"},{"name":"1 Center for non-coding RNA in Technology and Health, 2IBHV, University of Copenhagen, Gr\u00f8nneg\u00e5rdsvej 3, DK-1870 Frederiksberg, Denmark, 3Bioinformatics Group, Department of Computer Science, and Interdisciplinary Center for Bioinformatics, University of Leipzig, H\u00e4rtelstra\u00dfe 16-18, D-04107 Leipzig, 4Max Planck Institute for Mathematics in the Sciences, Inselstra\u00dfe 22, 5Fraunhofer Institut f\u00fcr Zelltherapie und Immunologie, Perlickstra\u00dfe 1, D-04103 Leipzig, Germany, 6Institute for Theoretical Chemistry, University of Vienna, W\u00e4hringerstra\u00dfe 17, A-1090 Vienna, Austria and 7The Santa Fe Institute, 1399 Hyde Park Road, Santa Fe, NM, USA"},{"name":"1 Center for non-coding RNA in Technology and Health, 2IBHV, University of Copenhagen, Gr\u00f8nneg\u00e5rdsvej 3, DK-1870 Frederiksberg, Denmark, 3Bioinformatics Group, Department of Computer Science, and Interdisciplinary Center for Bioinformatics, University of Leipzig, H\u00e4rtelstra\u00dfe 16-18, D-04107 Leipzig, 4Max Planck Institute for Mathematics in the Sciences, Inselstra\u00dfe 22, 5Fraunhofer Institut f\u00fcr Zelltherapie und Immunologie, Perlickstra\u00dfe 1, D-04103 Leipzig, Germany, 6Institute for Theoretical Chemistry, University of Vienna, W\u00e4hringerstra\u00dfe 17, A-1090 Vienna, Austria and 7The Santa Fe Institute, 1399 Hyde Park Road, Santa Fe, NM, USA"},{"name":"1 Center for non-coding RNA in Technology and Health, 2IBHV, University of Copenhagen, Gr\u00f8nneg\u00e5rdsvej 3, DK-1870 Frederiksberg, Denmark, 3Bioinformatics Group, Department of Computer Science, and Interdisciplinary Center for Bioinformatics, University of Leipzig, H\u00e4rtelstra\u00dfe 16-18, D-04107 Leipzig, 4Max Planck Institute for Mathematics in the Sciences, Inselstra\u00dfe 22, 5Fraunhofer Institut f\u00fcr Zelltherapie und Immunologie, Perlickstra\u00dfe 1, D-04103 Leipzig, Germany, 6Institute for Theoretical Chemistry, University of Vienna, W\u00e4hringerstra\u00dfe 17, A-1090 Vienna, Austria and 7The Santa Fe Institute, 1399 Hyde Park Road, Santa Fe, NM, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Gorodkin","sequence":"additional","affiliation":[{"name":"1 Center for non-coding RNA in Technology and Health, 2IBHV, University of Copenhagen, Gr\u00f8nneg\u00e5rdsvej 3, DK-1870 Frederiksberg, Denmark, 3Bioinformatics Group, Department of Computer Science, and Interdisciplinary Center for Bioinformatics, University of Leipzig, H\u00e4rtelstra\u00dfe 16-18, D-04107 Leipzig, 4Max Planck Institute for Mathematics in the Sciences, Inselstra\u00dfe 22, 5Fraunhofer Institut f\u00fcr Zelltherapie und Immunologie, Perlickstra\u00dfe 1, D-04103 Leipzig, Germany, 6Institute for Theoretical Chemistry, University of Vienna, W\u00e4hringerstra\u00dfe 17, A-1090 Vienna, Austria and 7The Santa Fe Institute, 1399 Hyde Park Road, Santa Fe, NM, USA"},{"name":"1 Center for non-coding RNA in Technology and Health, 2IBHV, University of Copenhagen, Gr\u00f8nneg\u00e5rdsvej 3, DK-1870 Frederiksberg, Denmark, 3Bioinformatics Group, Department of Computer Science, and Interdisciplinary Center for Bioinformatics, University of Leipzig, H\u00e4rtelstra\u00dfe 16-18, D-04107 Leipzig, 4Max Planck Institute for Mathematics in the Sciences, Inselstra\u00dfe 22, 5Fraunhofer Institut f\u00fcr Zelltherapie und Immunologie, Perlickstra\u00dfe 1, D-04103 Leipzig, Germany, 6Institute for Theoretical Chemistry, University of Vienna, W\u00e4hringerstra\u00dfe 17, A-1090 Vienna, Austria and 7The Santa Fe Institute, 1399 Hyde Park Road, Santa Fe, NM, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2010,12,1]]},"reference":[{"key":"2023012511543694000_B1","doi-asserted-by":"crossref","first-page":"W209","DOI":"10.1093\/nar\/gkp269","article-title":"UniPrime2: a web service providing easier Universal Primer design","volume":"37","author":"Boutros","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"2023012511543694000_B2","author":"Browser","year":"2010","journal-title":"The ucsc 44 way alignments"},{"key":"2023012511543694000_B3","doi-asserted-by":"crossref","first-page":"S18","DOI":"10.1101\/gr.3.3.S18","article-title":"Specificity, efficiency, and fidelity of PCR","volume":"3","author":"Cha","year":"1993","journal-title":"PCR Methods Appl."},{"key":"2023012511543694000_B4","doi-asserted-by":"crossref","first-page":"W95","DOI":"10.1093\/nar\/gkp377","article-title":"primers4clades: a web server that uses phylogenetic trees to design lineage-specific PCR primers 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