{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T13:31:44Z","timestamp":1770903104644,"version":"3.50.1"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"16","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Non-synonymous single nucleotide polymorphisms (nsSNPs) in voltage-gated potassium (Kv) channels cause diseases with potentially fatal consequences in seemingly healthy individuals. Identifying disease-causing genetic variation will aid presymptomatic diagnosis and treatment of such disorders. NsSNP-effect predictors are hypothesized to perform best when developed for specific gene families. We, thus, created KvSNP: a method that assigns a disease-causing probability to Kv-channel nsSNPs.<\/jats:p>\n               <jats:p>Results: KvSNP outperforms popular non gene-family-specific methods (SNPs&amp;GO, SIFT and Polyphen) in predicting the disease potential of Kv-channel variants, according to all tested metrics (accuracy, Matthews correlation coefficient and area under receiver operator characteristic curve). Most significantly, it increases the separation of the median predicted disease probabilities between benign and disease-causing SNPs by 26% on the next-best competitor. KvSNP has ranked 172 uncharacterized Kv-channel nsSNPs by disease-causing probability.<\/jats:p>\n               <jats:p>Availability and Implementation:KvSNP, a WEKA implementation is available at www.bioinformatics.leeds.ac.uk\/KvDB\/KvSNP.html.<\/jats:p>\n               <jats:p>Contact: \u00a0d.r.westhead@leeds.ac.uk<\/jats:p>\n               <jats:p>Supplementary Information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btr365","type":"journal-article","created":{"date-parts":[[2011,6,18]],"date-time":"2011-06-18T04:15:07Z","timestamp":1308370507000},"page":"2181-2186","source":"Crossref","is-referenced-by-count":27,"title":["KvSNP: accurately predicting the effect of genetic variants in voltage-gated potassium channels"],"prefix":"10.1093","volume":"27","author":[{"given":"L. F.","family":"Stead","sequence":"first","affiliation":[{"name":"1 Institute of Molecular and Cellular Biology, Faculty of Biological Sciences and 2Institute of Membrane and Systems Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK"}]},{"given":"I. C.","family":"Wood","sequence":"additional","affiliation":[{"name":"1 Institute of Molecular and Cellular Biology, Faculty of Biological Sciences and 2Institute of Membrane and Systems Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK"}]},{"given":"D. R.","family":"Westhead","sequence":"additional","affiliation":[{"name":"1 Institute of Molecular and Cellular Biology, Faculty of Biological Sciences and 2Institute of Membrane and Systems Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK"}]}],"member":"286","published-online":{"date-parts":[[2011,6,17]]},"reference":[{"key":"2023012511514265600_B1","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.4065\/78.12.1479","article-title":"Ethnic differences in cardiac potassium channel variants: Implications for genetic susceptibility to sudden cardiac death and genetic testing for congenital long QT syndrome","volume":"78","author":"Ackerman","year":"2003","journal-title":"Mayo Clin. Proc."},{"key":"2023012511514265600_B2","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1002\/prot.20441","article-title":"Combining prediction of secondary structure and solvent accessibility in proteins","volume":"59","author":"Adamczak","year":"2005","journal-title":"Proteins"},{"key":"2023012511514265600_B3","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1124\/jpet.103.054569","article-title":"Pharmacogenetic considerations in diseases of cardiac ion channels","volume":"307","author":"Anantharam","year":"2003","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"2023012511514265600_B4","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/1742-4682-3-15","article-title":"Amino acid size, charge, hydropathy indices and matrices for protein structure analysis","volume":"3","author":"Biro","year":"2006","journal-title":"Theor. Biol. Med. Model."},{"key":"2023012511514265600_B5","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1023\/A:1010933404324","article-title":"Random Forests","volume":"45","author":"Breiman","year":"2001","journal-title":"Mach. Learn."},{"key":"2023012511514265600_B6","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S0378-1119(99)00219-X","article-title":"The essence of SNPs","volume":"234","author":"Brookes","year":"1999","journal-title":"Gene"},{"key":"2023012511514265600_B7","doi-asserted-by":"crossref","first-page":"C496","DOI":"10.1152\/ajpcell.00464.2009","article-title":"Tetramerization domain mutations in KCNA5 affect channel kinetics and cause abnormal trafficking patterns","volume":"298","author":"Burg","year":"2010","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"2023012511514265600_B8","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1002\/humu.21047","article-title":"Functional annotations improve the predictive score of human disease-related mutations in proteins","volume":"30","author":"Calabrese","year":"2009","journal-title":"Hum. Mutat."},{"key":"2023012511514265600_B9","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1093\/bioinformatics\/btm270","article-title":"Predicting functionally important residues from sequence conservation","volume":"23","author":"Capra","year":"2007","journal-title":"Bioinformatics"},{"key":"2023012511514265600_B10","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1093\/bioinformatics\/btl649","article-title":"Deleterious SNP prediction: be mindful of your training data!","volume":"23","author":"Care","year":"2007","journal-title":"Bioinformatics"},{"key":"2023012511514265600_B11","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1093\/bioinformatics\/bth029","article-title":"Large-scale analysis of non-synonymous coding region single nucleotide polymorphisms","volume":"20","author":"Clifford","year":"2004","journal-title":"Bioinformatics"},{"key":"2023012511514265600_B12","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1161\/CIRCULATIONAHA.105.549071","article-title":"KCNH2-K897T is a genetic modifier of latent congenital long QT syndrome","volume":"112","author":"Crotti","year":"2005","journal-title":"Circulation"},{"key":"2023012511514265600_B13","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.1093\/bioinformatics\/btp445","article-title":"Fast and accurate predictions of protein stability changes upon mutations using statistical potentials and neural networks: PoPMuSiC-2.0","volume":"25","author":"Dehouck","year":"2009","journal-title":"Bioinformatics"},{"key":"2023012511514265600_B14","doi-asserted-by":"crossref","first-page":"2308","DOI":"10.1093\/bioinformatics\/btn454","article-title":"Improving position-specific predictions of protein functional sites using phylogenetic motifs","volume":"24","author":"Dukka Bahadur","year":"2008","journal-title":"Bioinformatics"},{"key":"2023012511514265600_B15","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1093\/bioinformatics\/14.9.755","article-title":"Profile hidden Markov models","volume":"14","author":"Eddy","year":"1998","journal-title":"Bioinformatics"},{"key":"2023012511514265600_B16","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1038\/nbt1008-1099","article-title":"Prepare for the deluge","volume":"26","author":"Editorial","year":"2008","journal-title":"Nat. Biotechnol."},{"key":"2023012511514265600_B17","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.ijbiomac.2009.11.009","article-title":"Sequence and structural analysis of binding site residues in protein-protein complexes","volume":"46","author":"Gromiha","year":"2010","journal-title":"Int. J. Biol. Macromol."},{"key":"2023012511514265600_B18","first-page":"359","article-title":"Correlation-based feature selection for discrete and numeric class machine learning","volume-title":"ICML '00: Proceedings of the Seventeenth International Conference on Machine Learning","author":"Hall","year":"2000"},{"key":"2023012511514265600_B19","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1145\/1656274.1656278","article-title":"The WEKA Data Mining Software: an update","volume":"11","author":"Hall","year":"2009","journal-title":"SIGKDD Expl."},{"key":"2023012511514265600_B20","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1186\/1471-2148-8-188","article-title":"Evolutionary analyses of KCNQ1 and HERG voltage-gated potassium channel sequences reveal location-specific susceptibility and augmented chemical severities of arrhythmogenic mutations","volume":"8","author":"Jackson","year":"2008","journal-title":"BMC Evol. Biol."},{"key":"2023012511514265600_B21","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1186\/1471-2105-7-417","article-title":"Searching for interpretable rules for disease mutations: a simulated annealing bump hunting strategy","volume":"7","author":"Jiang","year":"2006","journal-title":"BMC Bioinformatics"},{"key":"2023012511514265600_B22","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1086\/519747","article-title":"Sequence-based prioritization of nonsynonymous single-nucleotide polymorphisms for the study of disease mutations","volume":"81","author":"Jiang","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"2023012511514265600_B23","first-page":"338","article-title":"Estimating continuous distributions in bayesian classifiers","volume-title":"Proceedings of the Eleventh Conference on Uncertainty in Artificial Intelligence","author":"John","year":"1995"},{"key":"2023012511514265600_B24","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.cardiores.2005.04.005","article-title":"Susceptibility genes and modifiers for cardiac arrhythmias","volume":"67","author":"K\u00e4\u00e4b","year":"2005","journal-title":"Cardiovas. Res."},{"key":"2023012511514265600_B25","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/S0168-0102(02)00065-2","article-title":"Genetics of epilepsy: current status and perspectives","volume":"44","author":"Kaneko","year":"2002","journal-title":"Neurosci. Res."},{"key":"2023012511514265600_B26","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1161\/CIRCULATIONAHA.109.863076","article-title":"Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants","volume":"120","author":"Kapa","year":"2009","journal-title":"Circulation"},{"key":"2023012511514265600_B27","doi-asserted-by":"crossref","first-page":"2199","DOI":"10.1093\/bioinformatics\/btg297","article-title":"A comparative study of machine-learning methods to predict the effects of single nucleotide polymorphisms on protein function","volume":"19","author":"Krishnan","year":"2003","journal-title":"Bioinformatics"},{"key":"2023012511514265600_B28","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/S0092-8674(00)80556-5","article-title":"KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness","volume":"96","author":"Kubisch","year":"1999","journal-title":"Cell"},{"key":"2023012511514265600_B29","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1038\/nature06265","article-title":"Atomic structure of a voltage-dependent K+ channel in a lipid membrane-like environment","volume":"450","author":"Long","year":"2007","journal-title":"Nature"},{"key":"2023012511514265600_B30","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1172\/JCI27689","article-title":"SIDS: genetic and environmental influences may cause arrhythmia in this silent killer","volume":"116","author":"Makielski","year":"2006","journal-title":"J. Clin. Investig."},{"key":"2023012511514265600_B31","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1093\/molbev\/msh194","article-title":"Comparison of site-specific rate-inference methods for protein sequences: empirical bayesian methods are superior","volume":"21","author":"Mayrose","year":"2004","journal-title":"Mol. Biol. Evol."},{"key":"2023012511514265600_B32","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1101\/gr.176601","article-title":"Predicting deleterious amino acid substitutions","volume":"11","author":"Ng","year":"2001","journal-title":"Genome Res."},{"key":"2023012511514265600_B33","doi-asserted-by":"crossref","first-page":"3812","DOI":"10.1093\/nar\/gkg509","article-title":"SIFT: predicting amino acid changes that affect protein function","volume":"31","author":"Ng","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"2023012511514265600_B34","volume-title":"Heuristics: Intelligent Search Strategies for Computer Problem Solving","author":"Pearl","year":"1984"},{"key":"2023012511514265600_B35","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1007\/s00415-006-0134-y","article-title":"Chronic neuromyotonia as a phenotypic variation associated with a new mutation in the; KCNA1; gene","volume":"253","author":"Poujois","year":"2006","journal-title":"J. Neurol."},{"key":"2023012511514265600_B36","volume-title":"C4.5: Programs for Machine Learning","author":"Quinlan","year":"1993"},{"key":"2023012511514265600_B37","doi-asserted-by":"crossref","first-page":"3894","DOI":"10.1093\/nar\/gkf493","article-title":"Human non-synonymous SNPs: Server and survey","volume":"30","author":"Ramensky","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"2023012511514265600_B38","doi-asserted-by":"crossref","first-page":"C1837","DOI":"10.1152\/ajpcell.00405.2006","article-title":"Function of Kv1.5 channels and genetic variations of KCNA5 in patients with idiopathic pulmonary arterial hypertension","volume":"292","author":"Remillard","year":"2007","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"2023012511514265600_B39","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1006\/jmbi.1993.1626","article-title":"Comparative protein modelling by satisfaction of spatial restraints","volume":"234","author":"Sali","year":"1993","journal-title":"J. Mol. Biol."},{"key":"2023012511514265600_B40","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1007\/s004390050722","article-title":"Three novel KCNA1 mutations in episodic ataxia type I families","volume":"102","author":"Scheffer","year":"1998","journal-title":"Hum. Genet."},{"key":"2023012511514265600_B41","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1046\/j.1540-8167.2003.03339.x","article-title":"How really rare are rare diseases?: The intriguing case of independent compound mutations in the long QT syndrome","volume":"14","author":"Schwartz","year":"2003","journal-title":"J. Cardiovas. Electrophysiol."},{"key":"2023012511514265600_B42","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1111\/j.1540-8167.2007.01073.x","article-title":"The primary arrhythmia syndromes: Same mutation, different manifestations. Are we starting to understand why?","volume":"19","author":"Scicluna","year":"2008","journal-title":"J. Cardiovas. Electrophysiol."},{"key":"2023012511514265600_B43","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1093\/nar\/29.1.308","article-title":"dbSNP: the NCBI database of genetic variation","volume":"29","author":"Sherry","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"2023012511514265600_B44","doi-asserted-by":"crossref","first-page":"D815","DOI":"10.1093\/nar\/gkm659","article-title":"MutDB: update on development of tools for the biochemical analysis of genetic variation","volume":"36","author":"Singh","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"2023012511514265600_B45","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1161\/01.CIR.102.10.1178","article-title":"Spectrum of mutations in long-QT syndrome genes : KVLQT1, HERG, SCN5A, KCNE1, and KCNE2","volume":"102","author":"Splawski","year":"2000","journal-title":"Circulation"},{"key":"2023012511514265600_B46","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1002\/humu.21295","article-title":"KvDB; mining and mapping sequence variants in voltage-gated potassium channels","volume":"31","author":"Stead","year":"2010","journal-title":"Hum. Mutat."},{"key":"2023012511514265600_B47","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/gm13","article-title":"The Human Gene Mutation Database: 2008 update","volume":"1","author":"Stenson","year":"2009","journal-title":"Genome Med."},{"key":"2023012511514265600_B48","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1093\/hmg\/10.6.591","article-title":"Prediction of deleterious human alleles","volume":"10","author":"Sunyaev","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"2023012511514265600_B49","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1038\/nature05874","article-title":"Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project","volume":"447","author":"The ENCODE Consortium","year":"2007","journal-title":"Nature"},{"key":"2023012511514265600_B50","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1038\/nature02168","article-title":"The International HapMap Project","volume":"426","author":"The International HapMap Consortium","year":"2003","journal-title":"Nature"},{"key":"2023012511514265600_B51","doi-asserted-by":"crossref","first-page":"D169","DOI":"10.1093\/nar\/gkn664","article-title":"The Universal Protein Resource (UniProt) 2009","volume":"37","author":"The UniProt Consortium","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"2023012511514265600_B52","doi-asserted-by":"crossref","first-page":"2918","DOI":"10.1093\/bioinformatics\/btm437","article-title":"Accurate prediction of deleterious protein kinase polymorphisms","volume":"23","author":"Torkamani","year":"2007","journal-title":"Bioinformatics"},{"key":"2023012511514265600_B53","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/s00414-005-0019-0","article-title":"Sudden infant death syndrome and long QT syndrome: an epidemiological and genetic study","volume":"120","author":"Wedekind","year":"2006","journal-title":"Int. J. Legal Med."},{"key":"2023012511514265600_B54","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1016\/j.jmb.2005.12.025","article-title":"Identification and analysis of deleterious human SNPs","volume":"356","author":"Yue","year":"2006","journal-title":"J. Mol. Biol."}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/27\/16\/2181\/48863951\/bioinformatics_27_16_2181.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/27\/16\/2181\/48863951\/bioinformatics_27_16_2181.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T11:55:22Z","timestamp":1674647722000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/27\/16\/2181\/254180"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,6,17]]},"references-count":54,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2011,8,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btr365","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2011,8,15]]},"published":{"date-parts":[[2011,6,17]]}}}