{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T22:15:46Z","timestamp":1773958546084,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1008109","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T00:00:00Z","timestamp":1598400000000}}],"reference-count":74,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2020,8,14]],"date-time":"2020-08-14T00:00:00Z","timestamp":1597363200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["U01HL126273"],"award-info":[{"award-number":["U01HL126273"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL128537"],"award-info":[{"award-number":["R01HL128537"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL128170"],"award-info":[{"award-number":["R01HL128170"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["OT2OD026580"],"award-info":[{"award-number":["OT2OD026580"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001674","name":"Fondation Leducq","doi-asserted-by":"publisher","award":["18CVD05"],"award-info":[{"award-number":["18CVD05"]}],"id":[{"id":"10.13039\/501100001674","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000861","name":"Burroughs Wellcome Fund","doi-asserted-by":"publisher","award":["1015009"],"award-info":[{"award-number":["1015009"]}],"id":[{"id":"10.13039\/100000861","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["T32HL086350"],"award-info":[{"award-number":["T32HL086350"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1008109","type":"journal-article","created":{"date-parts":[[2020,8,14]],"date-time":"2020-08-14T19:33:03Z","timestamp":1597433583000},"page":"e1008109","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":29,"title":["A computational model of induced pluripotent stem-cell derived cardiomyocytes for high throughput risk stratification of KCNQ1 genetic variants"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8216-9744","authenticated-orcid":true,"given":"Divya C.","family":"Kernik","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5753-1131","authenticated-orcid":true,"given":"Pei-Chi","family":"Yang","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9098-0908","authenticated-orcid":true,"given":"Junko","family":"Kurokawa","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6068-8041","authenticated-orcid":true,"given":"Joseph C.","family":"Wu","sequence":"additional","affiliation":[]},{"given":"Colleen E.","family":"Clancy","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2020,8,14]]},"reference":[{"issue":"1","key":"pcbi.1008109.ref001","doi-asserted-by":"crossref","first-page":"29","DOI":"10.14797\/mdcj-10-1-29","article-title":"Genetics of long QT syndrome","volume":"10","author":"DJ Tester","year":"2014","journal-title":"Methodist Debakey Cardiovasc J"},{"issue":"15","key":"pcbi.1008109.ref002","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1161\/01.CIR.0000125524.34234.13","article-title":"Compound mutations: a common cause of severe long-QT syndrome","volume":"109","author":"P Westenskow","year":"2004","journal-title":"Circulation"},{"issue":"23","key":"pcbi.1008109.ref003","doi-asserted-by":"crossref","first-page":"2975","DOI":"10.1001\/jama.294.23.2975","article-title":"Genetic testing in the long QT syndrome: development and validation of an efficient approach to genotyping in clinical practice","volume":"294","author":"C Napolitano","year":"2005","journal-title":"JAMA"},{"issue":"6","key":"pcbi.1008109.ref004","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1093\/eurheartj\/ehr473","article-title":"Variants in the 3' untranslated region of the KCNQ1-encoded Kv7.1 potassium channel modify disease severity in patients with type 1 long QT syndrome in an allele-specific manner","volume":"33","author":"AS Amin","year":"2012","journal-title":"Eur Heart J"},{"issue":"12","key":"pcbi.1008109.ref005","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1056\/NEJM199209173271204","article-title":"The spectrum of symptoms and QT intervals in carriers of the gene for the long-QT syndrome","volume":"327","author":"GM Vincent","year":"1992","journal-title":"N Engl J Med"},{"issue":"1","key":"pcbi.1008109.ref006","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1161\/01.CIR.103.1.89","article-title":"Genotype-phenotype correlation in the long-QT syndrome: gene-specific triggers for life-threatening arrhythmias","volume":"103","author":"PJ Schwartz","year":"2001","journal-title":"Circulation"},{"issue":"24","key":"pcbi.1008109.ref007","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1016\/j.jacc.2008.02.068","article-title":"Long QT syndrome","volume":"51","author":"I Goldenberg","year":"2008","journal-title":"J Am Coll Cardiol"},{"issue":"3","key":"pcbi.1008109.ref008","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.stem.2016.07.006","article-title":"Transcriptome Profiling of Patient-Specific Human iPSC-Cardiomyocytes Predicts Individual Drug Safety and Efficacy Responses In Vitro","volume":"19","author":"E Matsa","year":"2016","journal-title":"Cell Stem Cell"},{"issue":"16","key":"pcbi.1008109.ref009","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1161\/CIRCULATIONAHA.113.001883","article-title":"Drug screening using a library of human induced pluripotent stem cell-derived cardiomyocytes reveals disease-specific patterns of cardiotoxicity","volume":"127","author":"P Liang","year":"2013","journal-title":"Circulation"},{"issue":"5","key":"pcbi.1008109.ref010","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/nm.4087","article-title":"Human induced pluripotent stem cell-derived cardiomyocytes recapitulate the predilection of breast cancer patients to doxorubicin-induced cardiotoxicity","volume":"22","author":"PW Burridge","year":"2016","journal-title":"Nat Med"},{"key":"pcbi.1008109.ref011","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s13287-015-0027-z","article-title":"Characterization of a novel KCNQ1 mutation for type 1 long QT syndrome and assessment of the therapeutic potential of a novel IKs activator using patient-specific induced pluripotent stem cell-derived cardiomyocytes","volume":"6","author":"D Ma","year":"2015","journal-title":"Stem Cell Res Ther"},{"issue":"15","key":"pcbi.1008109.ref012","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1056\/NEJMoa0908679","article-title":"Patient-specific induced pluripotent stem-cell models for long-QT syndrome","volume":"363","author":"A Moretti","year":"2010","journal-title":"N Engl J Med"},{"issue":"19","key":"pcbi.1008109.ref013","doi-asserted-by":"crossref","first-page":"2086","DOI":"10.1016\/j.jacc.2016.07.779","article-title":"Patient-Specific and Genome-Edited Induced Pluripotent Stem Cell-Derived Cardiomyocytes Elucidate Single-Cell Phenotype of Brugada Syndrome","volume":"68","author":"P Liang","year":"2016","journal-title":"J Am Coll Cardiol"},{"issue":"8","key":"pcbi.1008109.ref014","doi-asserted-by":"crossref","first-page":"2006","DOI":"10.1111\/jcmm.12581","article-title":"Functional abnormalities in iPSC-derived cardiomyocytes generated from CPVT1 and CPVT2 patients carrying ryanodine or calsequestrin mutations","volume":"19","author":"A Novak","year":"2015","journal-title":"J Cell Mol Med"},{"issue":"10","key":"pcbi.1008109.ref015","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1038\/ncb3411","article-title":"iPSC-derived cardiomyocytes reveal abnormal TGF-beta signalling in left ventricular non-compaction cardiomyopathy","volume":"18","author":"K Kodo","year":"2016","journal-title":"Nat Cell Biol"},{"issue":"12","key":"pcbi.1008109.ref016","doi-asserted-by":"crossref","first-page":"1958","DOI":"10.1161\/CIRCRESAHA.117.311080","article-title":"Induced Pluripotent Stem Cells 10 Years Later: For Cardiac Applications","volume":"120","author":"Y Yoshida","year":"2017","journal-title":"Circ Res"},{"issue":"3","key":"pcbi.1008109.ref017","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.bbrc.2009.07.052","article-title":"The effects of cardioactive drugs on cardiomyocytes derived from human induced pluripotent stem cells","volume":"387","author":"N Yokoo","year":"2009","journal-title":"Biochem Biophys Res Commun"},{"issue":"1","key":"pcbi.1008109.ref018","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.jacc.2018.04.041","article-title":"Genome Editing of Induced Pluripotent Stem Cells to Decipher Cardiac Channelopathy Variant","volume":"72","author":"P Garg","year":"2018","journal-title":"J Am Coll Cardiol"},{"issue":"11","key":"pcbi.1008109.ref019","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1016\/j.hrthm.2019.04.031","article-title":"Patient-independent human induced pluripotent stem cell model: A new tool for rapid determination of genetic variant pathogenicity in long QT syndrome","volume":"16","author":"NV Chavali","year":"2019","journal-title":"Heart Rhythm"},{"issue":"1","key":"pcbi.1008109.ref020","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.trsl.2012.08.005","article-title":"Determinants of incomplete penetrance and variable expressivity in heritable cardiac arrhythmia syndromes.","volume":"161","author":"JR Giudicessi","year":"2013","journal-title":"Transl Res."},{"issue":"17","key":"pcbi.1008109.ref021","doi-asserted-by":"crossref","first-page":"4125","DOI":"10.1113\/jphysiol.2013.254920","article-title":"Long QT syndrome: beyond the causal mutation","volume":"591","author":"AS Amin","year":"2013","journal-title":"J Physiol"},{"issue":"1","key":"pcbi.1008109.ref022","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s12265-012-9416-1","article-title":"Modeling long-QT syndromes with iPS cells.","volume":"6","author":"D Sinnecker","year":"2013","journal-title":"J Cardiovasc Transl Res"},{"issue":"6","key":"pcbi.1008109.ref023","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1113\/jphysiol.2014.279554","article-title":"A computational modelling approach combined with cellular electrophysiology data provides insights into the therapeutic benefit of targeting the late Na+ current","volume":"593","author":"PC Yang","year":"2015","journal-title":"J Physiol"},{"key":"pcbi.1008109.ref024","doi-asserted-by":"crossref","first-page":"668","DOI":"10.3389\/fphys.2017.00668","article-title":"Human In Silico Drug Trials Demonstrate Higher Accuracy than Animal Models in Predicting Clinical Pro-Arrhythmic Cardiotoxicity.","volume":"8","author":"E Passini","year":"2017","journal-title":"Front Physiol."},{"key":"pcbi.1008109.ref025","doi-asserted-by":"crossref","first-page":"958","DOI":"10.3389\/fphys.2018.00958","article-title":"A Heart for Diversity: Simulating Variability in Cardiac Arrhythmia Research.","volume":"9","author":"H Ni","year":"2018","journal-title":"Front Physiol"},{"issue":"11","key":"pcbi.1008109.ref026","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1016\/j.hrthm.2017.07.026","article-title":"Phenotypic variability in LQT3 human induced pluripotent stem cell-derived cardiomyocytes and their response to antiarrhythmic pharmacologic therapy: An in silico approach","volume":"14","author":"M Paci","year":"2017","journal-title":"Heart Rhythm"},{"issue":"23","key":"pcbi.1008109.ref027","doi-asserted-by":"crossref","first-page":"E2098","DOI":"10.1073\/pnas.1304382110","article-title":"Experimentally calibrated population of models predicts and explains intersubject variability in cardiac cellular electrophysiology","volume":"110","author":"OJ Britton","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1\u20133","key":"pcbi.1008109.ref028","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.pbiomolbio.2015.12.002","article-title":"Variability in cardiac electrophysiology: Using experimentally-calibrated populations of models to move beyond the single virtual physiological human paradigm","volume":"120","author":"A Muszkiewicz","year":"2016","journal-title":"Prog Biophys Mol Biol"},{"key":"pcbi.1008109.ref029","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/s41540-018-0047-2","article-title":"Population-based mechanistic modeling allows for quantitative predictions of drug responses across cell types","volume":"4","author":"JQX Gong","year":"2018","journal-title":"NPJ Syst Biol Appl"},{"issue":"11","key":"pcbi.1008109.ref030","doi-asserted-by":"crossref","first-page":"e002345","DOI":"10.1161\/CIRCGEN.118.002345","article-title":"High-Throughput Functional Evaluation of KCNQ1 Decrypts Variants of Unknown Significance.","volume":"11","author":"CG Vanoye","year":"2018","journal-title":"Circ Genom Precis Med."},{"issue":"17","key":"pcbi.1008109.ref031","doi-asserted-by":"crossref","first-page":"4533","DOI":"10.1113\/JP277724","article-title":"A computational model of induced pluripotent stem-cell derived cardiomyocytes incorporating experimental variability from multiple data sources","volume":"597","author":"DC Kernik","year":"2019","journal-title":"J Physiol"},{"key":"pcbi.1008109.ref032","doi-asserted-by":"crossref","first-page":"6955","DOI":"10.1038\/ncomms7955","article-title":"Correction of human phospholamban R14del mutation associated with cardiomyopathy using targeted nucleases and combination therapy.","volume":"6","author":"I Karakikes","year":"2015","journal-title":"Nat Commun."},{"issue":"D1","key":"pcbi.1008109.ref033","doi-asserted-by":"crossref","first-page":"D1062","DOI":"10.1093\/nar\/gkx1153","article-title":"ClinVar: improving access to variant interpretations and supporting evidence","volume":"46","author":"MJ Landrum","year":"2018","journal-title":"Nucleic Acids Res"},{"issue":"4","key":"pcbi.1008109.ref034","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1002\/cpt.367","article-title":"Improved Prediction of Drug-Induced Torsades de Pointes Through Simulations of Dynamics and Machine Learning Algorithms","volume":"100","author":"MC Lancaster","year":"2016","journal-title":"Clin Pharmacol Ther"},{"issue":"15","key":"pcbi.1008109.ref035","doi-asserted-by":"crossref","first-page":"2004","DOI":"10.1161\/01.CIR.103.15.2004","article-title":"Instability and triangulation of the action potential predict serious proarrhythmia, but action potential duration prolongation is antiarrhythmic","volume":"103","author":"LM Hondeghem","year":"2001","journal-title":"Circulation"},{"issue":"24","key":"pcbi.1008109.ref036","doi-asserted-by":"crossref","first-page":"2420","DOI":"10.1161\/01.CIR.97.24.2420","article-title":"A recessive variant of the Romano-Ward long-QT syndrome?","volume":"97","author":"SG Priori","year":"1998","journal-title":"Circulation"},{"issue":"8","key":"pcbi.1008109.ref037","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1016\/j.hrthm.2009.04.015","article-title":"Mutation in the S3 segment of KCNQ1 results in familial lone atrial fibrillation","volume":"6","author":"S Das","year":"2009","journal-title":"Heart Rhythm"},{"issue":"4","key":"pcbi.1008109.ref038","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1093\/cvr\/cvv196","article-title":"A new KCNQ1 mutation at the S5 segment that impairs its association with KCNE1 is responsible for short QT syndrome","volume":"107","author":"C Moreno","year":"2015","journal-title":"Cardiovasc Res"},{"key":"pcbi.1008109.ref039","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.pharmthera.2017.10.001","article-title":"The immature electrophysiological phenotype of iPSC-CMs still hampers in vitro drug screening: Special focus on IK1","volume":"183","author":"B Goversen","year":"2018","journal-title":"Pharmacol Ther"},{"issue":"2","key":"pcbi.1008109.ref040","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.jphs.2017.05.004","article-title":"Overexpression of KCNJ2 in induced pluripotent stem cell-derived cardiomyocytes for the assessment of QT-prolonging drugs.","volume":"134","author":"M Li","year":"2017","journal-title":"J Pharmacol Sci."},{"issue":"12","key":"pcbi.1008109.ref041","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1016\/j.hrthm.2013.09.061","article-title":"Electronic \"expression\" of the inward rectifier in cardiocytes derived from human-induced pluripotent stem cells.","volume":"10","author":"GC Bett","year":"2013","journal-title":"Heart Rhythm"},{"issue":"3","key":"pcbi.1008109.ref042","doi-asserted-by":"crossref","first-page":"eaar2631","DOI":"10.1126\/sciadv.aar2631","article-title":"Mechanisms of KCNQ1 channel dysfunction in long QT syndrome involving voltage sensor domain mutations.","volume":"4","author":"H Huang","year":"2018","journal-title":"Sci Adv."},{"issue":"4","key":"pcbi.1008109.ref043","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.hrthm.2017.11.032","article-title":"Using the genome aggregation database, computational pathogenicity prediction tools, and patch clamp heterologous expression studies to demote previously published long QT syndrome type 1 mutations from pathogenic to benign.","volume":"15","author":"DJ Clemens","year":"2018","journal-title":"Heart Rhythm."},{"key":"pcbi.1008109.ref044","unstructured":"National Center for Biotechnology Information. ClinVar [cited 2020 January 28]."},{"issue":"5","key":"pcbi.1008109.ref045","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.hrthm.2005.01.020","article-title":"Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing","volume":"2","author":"DJ Tester","year":"2005","journal-title":"Heart Rhythm"},{"key":"pcbi.1008109.ref046","article-title":"Functional phenotype variations of two novel KV 7.1 mutations identified in patients with Long QT syndrome","author":"S Hammami Bomholtz","journal-title":"Pacing Clin Electrophysiol"},{"issue":"11","key":"pcbi.1008109.ref047","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1046\/j.1540-8167.2003.03177.x","article-title":"Location of mutation in the KCNQ1 and phenotypic presentation of long QT syndrome","volume":"14","author":"W Zareba","year":"2003","journal-title":"J Cardiovasc Electrophysiol"},{"key":"pcbi.1008109.ref048","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/1471-2350-9-87","article-title":"Protective effect of KCNH2 single nucleotide polymorphism K897T in LQTS families and identification of novel KCNQ1 and KCNH2 mutations","volume":"9","author":"X Zhang","year":"2008","journal-title":"BMC Med Genet"},{"key":"pcbi.1008109.ref049","article-title":"Methods & compositions relating to drug-induced arrhythmia","author":"P Milos","year":"2005","journal-title":"Google Patents"},{"key":"pcbi.1008109.ref050","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.yjmcc.2016.09.011","article-title":"Convergence of models of human ventricular myocyte electrophysiology after global optimization to recapitulate clinical long QT phenotypes","volume":"100","author":"SA Mann","year":"2016","journal-title":"J Mol Cell Cardiol"},{"issue":"5","key":"pcbi.1008109.ref051","doi-asserted-by":"crossref","first-page":"e1002061","DOI":"10.1371\/journal.pcbi.1002061","article-title":"Simulation of the undiseased human cardiac ventricular action potential: model formulation and experimental validation.","volume":"7","author":"T O'Hara","year":"2011","journal-title":"PLoS Comput Biol."},{"issue":"2","key":"pcbi.1008109.ref052","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.hrthm.2011.09.066","article-title":"Arrhythmia formation in subclinical (\"silent\") long QT syndrome requires multiple insults: quantitative mechanistic study using the KCNQ1 mutation Q357R as example.","volume":"9","author":"T O'Hara","year":"2012","journal-title":"Heart Rhythm"},{"key":"pcbi.1008109.ref053","article-title":"The Promise and Peril of Precision Medicine: Phenotyping Still Matters Most","author":"JP Ackerman","year":"2016","journal-title":"Mayo Clin Proc"},{"issue":"9","key":"pcbi.1008109.ref054","doi-asserted-by":"crossref","first-page":"2778","DOI":"10.1161\/01.CIR.96.9.2778","article-title":"KVLQT1 C-terminal missense mutation causes a forme fruste long-QT syndrome","volume":"96","author":"C Donger","year":"1997","journal-title":"Circulation"},{"issue":"8","key":"pcbi.1008109.ref055","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1016\/j.hrthm.2018.03.038","article-title":"Long QT syndrome type 5-Lite: Defining the clinical phenotype associated with the potentially proarrhythmic p.Asp85Asn-KCNE1 common genetic variant","volume":"15","author":"CM Lane","year":"2018","journal-title":"Heart Rhythm"},{"issue":"6","key":"pcbi.1008109.ref056","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1136\/jmedgenet-2016-104153","article-title":"KCNQ1 p.L353L affects splicing and modifies the phenotype in a founder population with long QT syndrome type 1","volume":"54","author":"JD Kapplinger","year":"2017","journal-title":"J Med Genet"},{"issue":"1","key":"pcbi.1008109.ref057","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.hrthm.2013.10.005","article-title":"Single nucleotide polymorphisms in arrhythmia genes modify the risk of cardiac events and sudden death in long QT syndrome","volume":"11","author":"N Earle","year":"2014","journal-title":"Heart Rhythm"},{"issue":"2","key":"pcbi.1008109.ref058","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s00414-017-1739-7","article-title":"Influence of genetic modifiers on sudden cardiac death cases","volume":"132","author":"T Jenewein","year":"2018","journal-title":"Int J Legal Med"},{"issue":"17","key":"pcbi.1008109.ref059","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1161\/CIRCULATIONAHA.109.879643","article-title":"NOS1AP is a genetic modifier of the long-QT syndrome","volume":"120","author":"L Crotti","year":"2009","journal-title":"Circulation"},{"issue":"4","key":"pcbi.1008109.ref060","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1161\/01.CIR.99.4.529","article-title":"Low penetrance in the long-QT syndrome: clinical impact","volume":"99","author":"SG Priori","year":"1999","journal-title":"Circulation"},{"issue":"18","key":"pcbi.1008109.ref061","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1093\/eurheartj\/ehv695","article-title":"The genetics underlying acquired long QT syndrome: impact for genetic screening","volume":"37","author":"H Itoh","year":"2016","journal-title":"Eur Heart J"},{"issue":"19","key":"pcbi.1008109.ref062","doi-asserted-by":"crossref","first-page":"10613","DOI":"10.1073\/pnas.180223197","article-title":"A common polymorphism associated with antibiotic-induced cardiac arrhythmia","volume":"97","author":"F Sesti","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"pcbi.1008109.ref063","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1007\/s00109-003-0522-z","article-title":"Genetic variations of KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 in drug-induced long QT syndrome patients","volume":"82","author":"AD Paulussen","year":"2004","journal-title":"J Mol Med (Berl)."},{"issue":"16","key":"pcbi.1008109.ref064","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1161\/01.CIR.0000014448.19052.4C","article-title":"Allelic variants in long-QT disease genes in patients with drug-associated torsades de pointes","volume":"105","author":"P Yang","year":"2002","journal-title":"Circulation"},{"key":"pcbi.1008109.ref065","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.yjmcc.2015.08.015","article-title":"In silico screening of the impact of hERG channel kinetic abnormalities on channel block and susceptibility to acquired long QT syndrome","volume":"87","author":"L Romero","year":"2015","journal-title":"J Mol Cell Cardiol"},{"issue":"10","key":"pcbi.1008109.ref066","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1161\/01.CIR.101.10.1192","article-title":"Cellular arrhythmogenic effects of congenital and acquired long-QT syndrome in the heterogeneous myocardium","volume":"101","author":"PC Viswanathan","year":"2000","journal-title":"Circulation"},{"issue":"10","key":"pcbi.1008109.ref067","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1007\/s00439-013-1331-2","article-title":"Where genotype is not predictive of phenotype: towards an understanding of the molecular basis of reduced penetrance in human inherited disease","volume":"132","author":"DN Cooper","year":"2013","journal-title":"Hum Genet"},{"issue":"3","key":"pcbi.1008109.ref068","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.hrthm.2012.11.006","article-title":"Risk of life-threatening cardiac events among patients with long QT syndrome and multiple mutations","volume":"10","author":"J Mullally","year":"2013","journal-title":"Heart Rhythm"},{"issue":"5","key":"pcbi.1008109.ref069","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/j.yjmcc.2011.02.007","article-title":"Local control of beta-adrenergic stimulation: Effects on ventricular myocyte electrophysiology and Ca(2+)-transient.","volume":"50","author":"J Heijman","year":"2011","journal-title":"J Mol Cell Cardiol"},{"key":"pcbi.1008109.ref070","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.yjmcc.2020.04.009","article-title":"Quantitative analysis of variability in an integrated model of human ventricular electrophysiology and beta-adrenergic signaling","volume":"143","author":"JQX Gong","year":"2020","journal-title":"J Mol Cell Cardiol"},{"issue":"2","key":"pcbi.1008109.ref071","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.stemcr.2019.06.007","article-title":"Phenotype-Based High-Throughput Classification of Long QT Syndrome Subtypes Using Human Induced Pluripotent Stem Cells.","volume":"13","author":"D Yoshinaga","year":"2019","journal-title":"Stem Cell Reports"},{"issue":"1","key":"pcbi.1008109.ref072","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1093\/toxsci\/kfw200","article-title":"Comprehensive Translational Assessment of Human-Induced Pluripotent Stem Cell Derived Cardiomyocytes for Evaluating Drug-Induced Arrhythmias","volume":"155","author":"K Blinova","year":"2017","journal-title":"Toxicol Sci"},{"issue":"1","key":"pcbi.1008109.ref073","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1161\/CIRCRESAHA.117.305365","article-title":"Human induced pluripotent stem cell-derived cardiomyocytes: insights into molecular, cellular, and functional phenotypes","volume":"117","author":"I Karakikes","year":"2015","journal-title":"Circ Res"},{"issue":"1","key":"pcbi.1008109.ref074","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.mbs.2006.09.023","article-title":"Voltage noise influences action potential duration in cardiac myocytes","volume":"208","author":"AJ Tanskanen","year":"2007","journal-title":"Math Biosci"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1008109","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T00:00:00Z","timestamp":1598400000000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1008109","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T17:41:24Z","timestamp":1598463684000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1008109"}},"subtitle":[],"editor":[{"given":"Steven A.","family":"Niederer","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2020,8,14]]},"references-count":74,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,8,14]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1008109","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pcbi.1008109","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,14]]}}}