{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:47:15Z","timestamp":1788871635774,"version":"build-2803163510"},"reference-count":67,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,11,18]],"date-time":"2014-11-18T00:00:00Z","timestamp":1416268800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["BIO2012-40133"],"award-info":[{"award-number":["BIO2012-40133"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003751","name":"Ministerio de Sanidad, Servicios Sociales e Igualdad","doi-asserted-by":"publisher","award":["CP12\/03298"],"award-info":[{"award-number":["CP12\/03298"]}],"id":[{"id":"10.13039\/501100003751","id-type":"DOI","asserted-by":"publisher"}]},{"name":"EUSTROKE 7FP Health","award":["F2-08- 202213"],"award-info":[{"award-number":["F2-08- 202213"]}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00c3\u00b3n","doi-asserted-by":"crossref","award":["BFU2009-11527"],"award-info":[{"award-number":["BFU2009-11527"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Spanish stroke research network (INVICTUS)"},{"name":"Vall d'Hebron Institute of Research (VHIR)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Proteins"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Loss\u2010of\u2010function mutations of the enzyme alpha\u2010galactosidase A (GLA) causes Fabry disease (FD), that is a rare and potentially fatal disease. Identification of these pathological mutations by sequencing is important because it allows an early treatment of the disease. However, before taking any treatment decision, if the mutation identified is unknown, we first need to establish if it is pathological or not. General bioinformatic tools (PolyPhen\u20102, SIFT, Condel, etc.) can be used for this purpose, but their performance is still limited. Here we present a new tool, specifically derived for the assessment of GLA mutations. We first compared mutations of this enzyme known to cause FD with neutral sequence variants, using several structure and sequence properties. Then, we used these properties to develop a family of prediction methods adapted to different quality requirements. Trained and tested on a set of known Fabry mutations, our methods have a performance (Matthews correlation: 0.56\u20130.72) comparable or better than that of the more complex method, Polyphen\u20102 (Matthews correlation: 0.61), and better than those of SIFT (Matthews correl.: 0.54) and Condel (Matthews correl.: 0.51). This result is validated in an independent set of 65 pathological mutations, for which our method displayed the best success rate (91.0%, 87.7%, and 73.8%, for our method, PolyPhen\u20102 and SIFT, respectively). These data confirmed that our specific approach can effectively contribute to the identification of pathological mutations in GLA, and therefore enhance the use of sequence information in the identification of undiagnosed Fabry patients. Proteins 2015; 83:91\u2013104. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/prot.24708","type":"journal-article","created":{"date-parts":[[2014,11,8]],"date-time":"2014-11-08T02:52:24Z","timestamp":1415415144000},"page":"91-104","source":"Crossref","is-referenced-by-count":22,"title":["Molecular damage in\n                    <scp>F<\/scp>\n                    abry disease: Characterization and prediction of alpha\u2010galactosidase\n                    <scp>A<\/scp>\n                    pathological mutations"],"prefix":"10.1002","volume":"83","author":[{"given":"Casandra","family":"Riera","sequence":"first","affiliation":[{"name":"Research Unit in Translational Bioinformatics Institut de Recerca Hospital Vall d'Hebron (VHIR) Universitat Aut\u00f2noma de Barcelona Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Lois","sequence":"additional","affiliation":[{"name":"Research Unit in Translational Bioinformatics Institut de Recerca Hospital Vall d'Hebron (VHIR) Universitat Aut\u00f2noma de Barcelona Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Dom\u00ednguez","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology Research Centre for Nanomedicine Institut de Recerca Hospital Vall d'Hebron Barcelona Spain"},{"name":"Centre for Biomedical Research on Rare Diseases (CIBERER) Instituto de Salud Carlos III Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Israel","family":"Fernandez\u2010Cadenas","sequence":"additional","affiliation":[{"name":"Stroke Pharmacogenomics and Genetics Fundaci\u00f3 Docencia i Recerca Mutua Terrassa Terrassa Spain"},{"name":"Neurovascular Research Laboratory Institut de Recerca Hospital Vall d'Hebron Barcelona Spain"},{"name":"Neurovascular Unit Department of Neurology Universitat Aut\u00f2noma de Barcelona Hospital Universitari Vall d'Hebron Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan","family":"Montaner","sequence":"additional","affiliation":[{"name":"Neurovascular Research Laboratory Institut de Recerca Hospital Vall d'Hebron Barcelona Spain"},{"name":"Neurovascular Unit Department of Neurology Universitat Aut\u00f2noma de Barcelona Hospital Universitari Vall d'Hebron Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Rodr\u00edguez\u2010Sureda","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology Research Centre for Nanomedicine Institut de Recerca Hospital Vall d'Hebron Barcelona Spain"},{"name":"Centre for Biomedical Research on Rare Diseases (CIBERER) Instituto de Salud Carlos III Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"de la Cruz","sequence":"additional","affiliation":[{"name":"Research Unit in Translational Bioinformatics Institut de Recerca Hospital Vall d'Hebron (VHIR) Universitat Aut\u00f2noma de Barcelona Barcelona Spain"},{"name":"Instituci\u00f3 Catalana de Recerca i Estudis Avan\u00e7ats (ICREA) Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,11,18]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"3733","volume-title":"The metabolic and molecular bases of inherited disease","author":"Desnick RJ","year":"2005"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1086\/504601"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.285.21.2743"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1086\/318809"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2008.065904"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)61493-8"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-4-21"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21530"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2008.02.050"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfq073"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfq080"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfr025"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2011.178"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.112.002642"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg509"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.03.004"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0068370"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm238"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22225"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/wcms.1170"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds385"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2001.5255"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2004.01.035"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1096-7192(02)00151-8"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.20252"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1136\/amiajnl-2011-000309"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-13-S4-S3"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btm437"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10032"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr365"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.01.011"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki070"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1991.tb03870.x"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10275"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.6.591"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh340"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btm098"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/25.17.3389"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4165(76)90017-9"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.6.2540"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000043901.45141.D4"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20130825"},{"key":"e_1_2_6_45_1","first-page":"353","volume-title":"Protein folding","author":"Creighton T","year":"1992"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.22.10915"},{"key":"e_1_2_6_47_1","volume-title":"\u201cNACCESS\u201d, Computer Program. Department of Biochemistry and Molecular Biology","author":"Hubbard SJ","year":"1993"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki387"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.176601"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1145\/1656274.1656278"},{"key":"e_1_2_6_51_1","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1093\/oso\/9780198538493.001.0001","volume-title":"Neural networks for pattern recognition","author":"Bishop CM","year":"1995"},{"key":"e_1_2_6_52_1","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1613\/jair.953","article-title":"SMOTE: synthetic minority over\u2010sampling technique","volume":"16","author":"Chawla N","year":"2002","journal-title":"J Artif Intell Res"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0067863"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/16.5.412"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-13-S4-S2"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.10522"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2005.08.020"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00483a001"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2006.09.053"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21242"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki375"},{"key":"e_1_2_6_62_1","doi-asserted-by":"publisher","DOI":"10.1110\/ps.0217002"},{"key":"e_1_2_6_63_1","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1186\/1471-2164-14-S3-S4","article-title":"The SAAP database and pipeline: tools to analyze the impact and predict the pathogenicity of mutations","volume":"14","author":"Al\u2010Numair NS","year":"2013","journal-title":"BMC Genom"},{"key":"e_1_2_6_64_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-10-S8-S8"},{"key":"e_1_2_6_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(94)90032-9"},{"key":"e_1_2_6_66_1","doi-asserted-by":"publisher","DOI":"10.1021\/j100785a001"},{"key":"e_1_2_6_67_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btg297"},{"issue":"2","key":"e_1_2_6_68_1","first-page":"1","article-title":"Physician and patient perceptions regarding physician training in rare diseases: the need for stronger educational initiatives for physicians","volume":"1","author":"Engel PA","year":"2013","journal-title":"J Rare Disord"}],"container-title":["Proteins: Structure, Function, and Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fprot.24708","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prot.24708","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T17:44:44Z","timestamp":1717523084000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/prot.24708"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,11,18]]},"references-count":67,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2015,1]]}},"alternative-id":["10.1002\/prot.24708"],"URL":"https:\/\/doi.org\/10.1002\/prot.24708","archive":["Portico"],"relation":{},"ISSN":["0887-3585","1097-0134"],"issn-type":[{"value":"0887-3585","type":"print"},{"value":"1097-0134","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,11,18]]}}}