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Some results are presented suggesting that template-based methods are significantly more accurate than simpler alternative methods. The validation of existing methods is also discussed at length with the detailed description of recent results and some suggestions for future validation strategies. The last part of the review addresses future challenges for multiple sequence alignment methods in the genomic era, most notably the need to cope with very large sequences, the need to integrate large amounts of experimental data, the need to accurately align non-coding and non-transcribed sequences and finally, the need to integrate many alternative methods and approaches.<\/jats:p><jats:p>Contact: \u00a0cedric.notredame@crg.es<\/jats:p>","DOI":"10.1093\/bioinformatics\/btp452","type":"journal-article","created":{"date-parts":[[2009,8,1]],"date-time":"2009-08-01T00:14:58Z","timestamp":1249085698000},"page":"2455-2465","source":"Crossref","is-referenced-by-count":182,"title":["Upcoming challenges for multiple sequence alignment methods in the high-throughput era"],"prefix":"10.1093","volume":"25","author":[{"given":"Carsten","family":"Kemena","sequence":"first","affiliation":[{"name":"Centre For Genomic Regulation (Pompeus Fabre University), Carrer del Doctor Aiguader 88, 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cedric","family":"Notredame","sequence":"additional","affiliation":[{"name":"Centre For Genomic Regulation (Pompeus Fabre University), Carrer del Doctor Aiguader 88, 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,7,30]]},"reference":[{"key":"2023013112123467200_B1","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1093\/molbev\/msl002","article-title":"Prediction of function divergence in protein families using the substitution rate variation parameter alpha","volume":"23","author":"Abhiman","year":"2006","journal-title":"Mol. 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