{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T04:22:09Z","timestamp":1770524529307,"version":"3.49.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"17","license":[{"start":{"date-parts":[[2017,4,13]],"date-time":"2017-04-13T00:00:00Z","timestamp":1492041600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"BBSRC","doi-asserted-by":"publisher","award":["BB\/M011712\/1"],"award-info":[{"award-number":["BB\/M011712\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Motivation<\/jats:title><jats:p>Protein fold recognition when appropriate, evolutionarily-related, structural templates can be identified is often trivial and may even be viewed as a solved problem. However in cases where no homologous structural templates can be detected, fold recognition is a notoriously difficult problem (Moult et al., 2014). Here we present EigenTHREADER, a novel fold recognition method capable of identifying folds where no homologous structures can be identified. EigenTHREADER takes a query amino acid sequence, generates a map of intra-residue contacts, and then searches a library of contact maps of known structures. To allow the contact maps to be compared, we use eigenvector decomposition to resolve the principal eigenvectors these can then be aligned using standard dynamic programming algorithms. The approach is similar to the Al-Eigen approach of Di Lena et al. (2010), but with improvements made both to speed and accuracy. With this search strategy, EigenTHREADER does not depend directly on sequence homology between the target protein and entries in the fold library to generate models. This in turn enables EigenTHREADER to correctly identify analogous folds where little or no sequence homology information is.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>EigenTHREADER outperforms well-established fold recognition methods such as pGenTHREADER and HHSearch in terms of True Positive Rate in the difficult task of analogous fold recognition. This should allow template-based modelling to be extended to many new protein families that were previously intractable to homology based fold recognition methods.<\/jats:p><\/jats:sec><jats:sec><jats:title>Availability and implementation<\/jats:title><jats:p>All code used to generate these results and the computational protocol can be downloaded from https:\/\/github.com\/DanBuchan\/eigen_scripts. EigenTHREADER, the benchmark code and the data this paper is based on can be downloaded from: http:\/\/bioinfadmin.cs.ucl.ac.uk\/downloads\/eigenTHREADER\/.<\/jats:p><\/jats:sec>","DOI":"10.1093\/bioinformatics\/btx217","type":"journal-article","created":{"date-parts":[[2017,4,12]],"date-time":"2017-04-12T19:12:20Z","timestamp":1492024340000},"page":"2684-2690","source":"Crossref","is-referenced-by-count":64,"title":["EigenTHREADER: analogous protein fold recognition by efficient contact map threading"],"prefix":"10.1093","volume":"33","author":[{"given":"Daniel W A","family":"Buchan","sequence":"first","affiliation":[{"name":"Department of Computer Science, University College London, Gower Street, London, UK"}]},{"given":"David T","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Computer Science, University College London, Gower Street, London, UK"}]}],"member":"286","published-online":{"date-parts":[[2017,4,13]]},"reference":[{"key":"2023020206282044900_btx217-B1","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The Protein Data Bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Res"},{"key":"2023020206282044900_btx217-B2","volume-title":"Proteins: Structures and Molecular Properties","author":"Creighton","year":"1992"},{"key":"2023020206282044900_btx217-B3","doi-asserted-by":"crossref","first-page":"2250","DOI":"10.1093\/bioinformatics\/btq402","article-title":"Fast overlapping of protein contact maps by alignment of eigenvectors","volume":"26","author":"Di Lena","year":"2010","journal-title":"Bioinformatics"},{"key":"2023020206282044900_btx217-B4","doi-asserted-by":"crossref","first-page":"22.","DOI":"10.1186\/1471-2105-15-22","article-title":"BioShell-Threading: versatile Monte Carlo package for protein 3D threading","volume":"15","author":"Gniewek","year":"2014","journal-title":"BMC Bioinformatics"},{"key":"2023020206282044900_btx217-B5","first-page":"512","volume-title":"FOCS 1999 Proceedings of the 40th Annual Sumposium on Foundation of Computer Science","author":"Goldman","year":"1999"},{"key":"2023020206282044900_btx217-B6","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1093\/bioinformatics\/btr638","article-title":"PSICOV: precise structural contact prediction using sparse inverse covariance estimation on large multiple sequence alignments","volume":"28","author":"Jones","year":"2012","journal-title":"Bioinformatics"},{"key":"2023020206282044900_btx217-B7","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1093\/bioinformatics\/btu791","article-title":"MetaPSICOV: combining coevolution methods for accurate prediction of contacts and long range hydrogen bonding in proteins","volume":"31","author":"Jones","year":"2015","journal-title":"Bioinformatics"},{"key":"2023020206282044900_btx217-B8","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/358086a0","article-title":"A new approach to protein fold recognition","volume":"358","author":"Jones","year":"1992","journal-title":"Nature"},{"key":"2023020206282044900_btx217-B9","doi-asserted-by":"crossref","first-page":"85.","DOI":"10.1186\/1471-2105-15-85","article-title":"FreeContact: fast and free software for protein contact prediction from residue co-evolution","volume":"15","author":"Kaj\u00e1n","year":"2014","journal-title":"BMC Bioinformatics"},{"key":"2023020206282044900_btx217-B10","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1002\/prot.25020","article-title":"Assessment of CASP11 contact-assisted predictions","volume":"84","author":"Kinch","year":"2016","journal-title":"Proteins"},{"key":"2023020206282044900_btx217-B11","doi-asserted-by":"crossref","first-page":"e92197.","DOI":"10.1371\/journal.pone.0092197","article-title":"De novo structure prediction of globular proteins aided by sequence variation-derived contacts","volume":"9","author":"Kosciolek","year":"2014","journal-title":"PLoS One"},{"key":"2023020206282044900_btx217-B12","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1093\/bioinformatics\/btp302","article-title":"pGenTHREADER and pDomTHREADER: new methods for improved protein fold recognition and superfamily discrimination","volume":"25","author":"Lobley","year":"2009","journal-title":"Bioinformatics"},{"key":"2023020206282044900_btx217-B13","doi-asserted-by":"crossref","first-page":"e1003500.","DOI":"10.1371\/journal.pcbi.1003500","article-title":"MRFalign: protein homology detection through alignment of Markov random fields","volume":"10","author":"Ma","year":"2014","journal-title":"PLoS Comput. 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