{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T19:23:21Z","timestamp":1770233001726,"version":"3.49.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"W1","license":[{"start":{"date-parts":[[2020,5,25]],"date-time":"2020-05-25T00:00:00Z","timestamp":1590364800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,7,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The rapid expansion of high-quality genome assemblies, exemplified by ongoing initiatives such as the Genome-10K and i5k, demands novel automated methods to approach comparative genomics. Of these, the study of inactivating mutations in the coding region of genes, or pseudogenization,\u00a0as a source of evolutionary novelty is mostly overlooked. Thus, to address such evolutionary\/genomic events, a systematic, accurate and computationally automated approach is required. Here, we present PseudoChecker, the first integrated online platform for gene inactivation\u00a0inference. Unlike the few existing methods, our comparative genomics-based approach displays full automation, a built-in graphical user interface and a novel index,\u00a0PseudoIndex,\u00a0for an empirical evaluation of the gene coding status. As a multi-platform online service, PseudoChecker simplifies access and usability, allowing a fast identification of disruptive mutations. An analysis of 30 genes previously reported to be eroded in mammals, and 30 viable genes from the same lineages, demonstrated that PseudoChecker was able to correctly infer 97% of loss events and 95% of functional genes, confirming its reliability. PseudoChecker\u00a0is freely available, without login required, at http:\/\/pseudochecker.ciimar.up.pt.<\/jats:p>","DOI":"10.1093\/nar\/gkaa408","type":"journal-article","created":{"date-parts":[[2020,5,6]],"date-time":"2020-05-06T19:09:27Z","timestamp":1588792167000},"page":"W321-W331","source":"Crossref","is-referenced-by-count":23,"title":["PseudoChecker: an integrated online platform for gene inactivation inference"],"prefix":"10.1093","volume":"48","author":[{"given":"Lu\u00eds Q","family":"Alves","sequence":"first","affiliation":[{"name":"CIIMAR-Interdisciplinary Centre of Marine and Environmental Research, U. Porto-University of Porto, Matosinhos, 4450-208, Portugal"}]},{"given":"Raquel","family":"Ruivo","sequence":"first","affiliation":[{"name":"CIIMAR-Interdisciplinary Centre of Marine and Environmental Research, U. Porto-University of Porto, Matosinhos, 4450-208, Portugal"}]},{"given":"Miguel M","family":"Fonseca","sequence":"first","affiliation":[{"name":"CIIMAR-Interdisciplinary Centre of Marine and Environmental Research, U. Porto-University of Porto, Matosinhos, 4450-208, Portugal"}]},{"given":"M\u00f3nica","family":"Lopes-Marques","sequence":"first","affiliation":[{"name":"CIIMAR-Interdisciplinary Centre of Marine and Environmental Research, U. Porto-University of Porto, Matosinhos, 4450-208, Portugal"}]},{"given":"Pedro","family":"Ribeiro","sequence":"first","affiliation":[{"name":"CRACS\u00a0& INESC-TEC Department of Computer Science, FCUP, Porto, 4169-007, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7697-386X","authenticated-orcid":false,"given":"L\u00a0Filipe\u00a0C","family":"Castro","sequence":"first","affiliation":[{"name":"CIIMAR-Interdisciplinary Centre of Marine and Environmental Research, U. Porto-University of Porto, Matosinhos, 4450-208, Portugal"},{"name":"Department of Biology, FCUP, Porto, 4169-007, Portugal"}]}],"member":"286","published-online":{"date-parts":[[2020,5,25]]},"reference":[{"key":"2020062614045757900_B1","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1038\/s41467-018-03667-1","article-title":"A genomics approach reveals insights into the importance of gene losses for mammalian adaptations","volume":"9","author":"Sharma","year":"2018","journal-title":"Nat. Commun."},{"key":"2020062614045757900_B2","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/nrg.2016.39","article-title":"Evolution by gene loss","volume":"17","author":"Albalat","year":"2016","journal-title":"Nat. Rev. Genet."},{"key":"2020062614045757900_B3","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/S0014-5793(00)01199-6","article-title":"Vertebrate pseudogenes","volume":"468","author":"Mighell","year":"2000","journal-title":"FEBS Lett."},{"key":"2020062614045757900_B4","doi-asserted-by":"crossref","first-page":"112","DOI":"10.2174\/157489309788184792","article-title":"Current trends in pseudogene detection and characterization","volume":"4","author":"Rouchka","year":"2009","journal-title":"Curr. Bioinform."},{"key":"2020062614045757900_B5","doi-asserted-by":"crossref","first-page":"3644","DOI":"10.1038\/ncomms4644","article-title":"Processed pseudogenes acquired somatically during cancer development","volume":"5","author":"Cooke","year":"2014","journal-title":"Nat. Commun."},{"key":"2020062614045757900_B6","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1007\/s00251-018-1071-5","article-title":"Cetacea are natural knockouts for IL20","volume":"70","author":"Lopes-Marques","year":"2018","journal-title":"Immunogenetics"},{"key":"2020062614045757900_B7","first-page":"3179","article-title":"Transition to an aquatic habitat permitted the repeated loss of the pleiotropic KLK8 gene in mammals","volume":"9","author":"Hecker","year":"2017","journal-title":"Genome Biol. Evol."},{"key":"2020062614045757900_B8","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.2005293","article-title":"Loss of RXFP2 and INSL3 genes in Afrotheria shows that testicular descent is the ancestral condition in placental mammals","volume":"16","author":"Sharma","year":"2018","journal-title":"PLoS Biol."},{"key":"2020062614045757900_B9","doi-asserted-by":"crossref","first-page":"eaat9660","DOI":"10.1126\/sciadv.aat9660","article-title":"Molecular parallelism in fast-twitch muscle proteins in echolocating mammals","volume":"4","author":"Lee","year":"2018","journal-title":"Sci. Adv."},{"key":"2020062614045757900_B10","doi-asserted-by":"crossref","first-page":"e38906","DOI":"10.7554\/eLife.38906","article-title":"Recurrent loss of HMGCS2 shows that ketogenesis is not essential for the evolution of large mammalian brains","volume":"7","author":"Jebb","year":"2018","journal-title":"Elife"},{"key":"2020062614045757900_B11","doi-asserted-by":"crossref","first-page":"3211","DOI":"10.1093\/gbe\/evy243","article-title":"Loss of enzymes in the bile acid synthesis pathway explains differences in bile composition among mammals","volume":"10","author":"Sharma","year":"2018","journal-title":"Genome Biol. Evol."},{"key":"2020062614045757900_B12","doi-asserted-by":"crossref","first-page":"3036","DOI":"10.1073\/pnas.1818504116","article-title":"Convergent gene losses illuminate metabolic and physiological changes in herbivores and carnivores","volume":"116","author":"Hecker","year":"2019","journal-title":"Proc. Natl. Acad. Sci."},{"key":"2020062614045757900_B13","doi-asserted-by":"crossref","first-page":"3656","DOI":"10.1111\/mec.15180","article-title":"Convergent vomeronasal system reduction in mammals coincides with convergent losses of calcium signalling and odorant-degrading genes","volume":"28","author":"Hecker","year":"2019","journal-title":"Mol. Ecol."},{"key":"2020062614045757900_B14","doi-asserted-by":"crossref","first-page":"eaaw6671","DOI":"10.1126\/sciadv.aaw6671","article-title":"Genes lost during the transition from land to water in cetaceans highlight genomic changes associated with aquatic adaptations","volume":"5","author":"Huelsmann","year":"2019","journal-title":"Sci. Adv."},{"key":"2020062614045757900_B15","doi-asserted-by":"crossref","first-page":"lqz012","DOI":"10.1093\/nargab\/lqz012","article-title":"Losses of human disease-associated genes in placental mammals","volume":"2","author":"Sharma","year":"2020","journal-title":"NAR Genomics Bioinform."},{"key":"2020062614045757900_B16","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/s41559-020-1129-2","article-title":"Widespread patterns of gene loss in the evolution of the animal kingdom","volume":"4","author":"Guijarro-Clarke","year":"2020","journal-title":"Nat. Ecol. Evol."},{"key":"2020062614045757900_B17","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s12862-019-1359-6","article-title":"Odontogenic ameloblast-associated (ODAM) is inactivated in toothless\/enamelless placental mammals and toothed whales","volume":"19","author":"Springer","year":"2019","journal-title":"BMC Evol. Biol."},{"key":"2020062614045757900_B18","doi-asserted-by":"crossref","first-page":"e52","DOI":"10.1371\/journal.pbio.0040052","article-title":"Gene losses during human origins","volume":"4","author":"Wang","year":"2006","journal-title":"PLoS Biol."},{"key":"2020062614045757900_B19","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1093\/molbev\/msz068","article-title":"Complete inactivation of sebum-producing genes parallels the loss of sebaceous glands in Cetacea","volume":"36","author":"Lopes-Marques","year":"2019","journal-title":"Mol. Biol. Evol."},{"key":"2020062614045757900_B20","doi-asserted-by":"crossref","first-page":"121","DOI":"10.3390\/genes10020121","article-title":"The singularity of Cetacea behavior parallels the complete inactivation of melatonin gene modules","volume":"10","author":"Lopes-Marques","year":"2019","journal-title":"Genes"},{"key":"2020062614045757900_B21","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1007\/s00251-019-01114-z","article-title":"Convergent inactivation of the skin-specific CC motif chemokine ligand 27 in mammalian evolution","volume":"71","author":"Lopes-Marques","year":"2019","journal-title":"Immunogenetics"},{"key":"2020062614045757900_B22","doi-asserted-by":"crossref","first-page":"e7758","DOI":"10.7717\/peerj.7758","article-title":"The dopamine receptor D5 gene shows signs of independent erosion in toothed and baleen whales","volume":"7","author":"Alves","year":"2019","journal-title":"Peer J."},{"key":"2020062614045757900_B23","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1086\/302219","article-title":"When less is more: gene loss as an engine of evolutionary change","volume":"64","author":"Olson","year":"1999","journal-title":"Am. J. Human Genet."},{"key":"2020062614045757900_B24","doi-asserted-by":"crossref","first-page":"eaar6478","DOI":"10.1126\/sciadv.aar6478","article-title":"Chitinase genes (CHIAs) provide genomic footprints of a post-Cretaceous dietary radiation in placental mammals","volume":"4","author":"Emerling","year":"2018","journal-title":"Sci. Adv."},{"key":"2020062614045757900_B25","doi-asserted-by":"crossref","first-page":"e1602878","DOI":"10.1126\/sciadv.1602878","article-title":"Inactivation of thermogenic UCP1 as a historical contingency in multiple placental mammal clades","volume":"3","author":"Gaudry","year":"2017","journal-title":"Sci. Adv."},{"key":"2020062614045757900_B26","doi-asserted-by":"crossref","first-page":"1254390","DOI":"10.1126\/science.1254390","article-title":"Evidence for a single loss of mineralized teeth in the common avian ancestor","volume":"346","author":"Meredith","year":"2014","journal-title":"Science"},{"key":"2020062614045757900_B27","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1126\/science.aap7714","article-title":"Ancient convergent losses of Paraoxonase 1 yield potential risks for modern marine mammals","volume":"361","author":"Meyer","year":"2018","journal-title":"Science"},{"key":"2020062614045757900_B28","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1126\/science.1253451","article-title":"Whole-genome analyses resolve early branches in the tree of life of modern birds","volume":"346","author":"Jarvis","year":"2014","journal-title":"Science"},{"key":"2020062614045757900_B29","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1093\/jhered\/esp086","article-title":"Genome 10K: a proposal to obtain whole-genome sequence for 10 000 vertebrate species","volume":"100","author":"Scientists","year":"2009","journal-title":"J. Hered."},{"key":"2020062614045757900_B30","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1126\/science.331.6023.1386","article-title":"Creating a buzz about insect genomes","volume":"331","author":"Robinson","year":"2011","journal-title":"Science"},{"key":"2020062614045757900_B31","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1136\/jmedgenet-2017-104837","article-title":"Their loss is our gain: regressive evolution in vertebrates provides genomic models for uncovering human disease loci","volume":"54","author":"Emerling","year":"2017","journal-title":"J. Med. Genet."},{"key":"2020062614045757900_B32","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1186\/1471-2164-9-466","article-title":"Retrocopy contributions to the evolution of the human genome","volume":"9","author":"Baertsch","year":"2008","journal-title":"BMC Genomics"},{"key":"2020062614045757900_B33","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1093\/bioinformatics\/btl116","article-title":"PseudoPipe: an automated pseudogene identification pipeline","volume":"22","author":"Zhang","year":"2006","journal-title":"Bioinformatics"},{"key":"2020062614045757900_B34","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1101\/gr.4766206","article-title":"Iterative gene prediction and pseudogene removal improves genome annotation","volume":"16","author":"van\u00a0Baren","year":"2006","journal-title":"Genome Res."},{"key":"2020062614045757900_B35","doi-asserted-by":"crossref","first-page":"R26","DOI":"10.1186\/gb-2010-11-3-r26","article-title":"Identification and analysis of unitary pseudogenes: historic and contemporary gene losses in humans and other primates","volume":"11","author":"Zhang","year":"2010","journal-title":"Genome Biol."},{"key":"2020062614045757900_B36","doi-asserted-by":"crossref","first-page":"e103","DOI":"10.1093\/nar\/gkw210","article-title":"Coding exon-structure aware realigner (CESAR) utilizes genome alignments for accurate comparative gene annotation","volume":"44","author":"Sharma","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"2020062614045757900_B37","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/0022-2836(70)90057-4","article-title":"A general method applicable to the search for similarities in the amino acid sequence of two proteins","volume":"48","author":"Needleman","year":"1970","journal-title":"J. Mol. Biol."},{"key":"2020062614045757900_B38","doi-asserted-by":"crossref","first-page":"2582","DOI":"10.1093\/molbev\/msy159","article-title":"MACSE v2: toolkit for the alignment of coding sequences accounting for frameshifts and stop codons","volume":"35","author":"Ranwez","year":"2018","journal-title":"Mol. Biol. Evol."},{"key":"2020062614045757900_B39","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1093\/molbev\/msz111","article-title":"Unprecedented parallel photosynthetic losses in a heterotrophic orchid genus","volume":"36","author":"Barrett","year":"2019","journal-title":"Mol. Biol. Evol."},{"key":"2020062614045757900_B40","doi-asserted-by":"crossref","first-page":"1260419","DOI":"10.1126\/science.1260419","article-title":"Tissue-based map of the human proteome","volume":"347","author":"Uhl\u00e9n","year":"2015","journal-title":"Science"},{"key":"2020062614045757900_B41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/jmammal\/gyx147","article-title":"How many species of mammals are there?","volume":"99","author":"Burgin","year":"2018","journal-title":"J. Mammal."},{"key":"2020062614045757900_B42","doi-asserted-by":"crossref","first-page":"D55","DOI":"10.1093\/nar\/gkl851","article-title":"Pseudogene. org: a comprehensive database and comparison platform for pseudogene annotation","volume":"35","author":"Karro","year":"2007","journal-title":"Nucleic Acids Res."}],"container-title":["Nucleic Acids Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/nar\/article-pdf\/48\/W1\/W321\/33433377\/gkaa408.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/nar\/article-pdf\/48\/W1\/W321\/33433377\/gkaa408.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,6,27]],"date-time":"2020-06-27T06:41:56Z","timestamp":1593240116000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/nar\/article\/48\/W1\/W321\/5843816"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,25]]},"references-count":42,"journal-issue":{"issue":"W1","published-online":{"date-parts":[[2020,5,25]]},"published-print":{"date-parts":[[2020,7,2]]}},"URL":"https:\/\/doi.org\/10.1093\/nar\/gkaa408","relation":{},"ISSN":["0305-1048","1362-4962"],"issn-type":[{"value":"0305-1048","type":"print"},{"value":"1362-4962","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,7,2]]},"published":{"date-parts":[[2020,5,25]]}}}