{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,5]],"date-time":"2026-04-05T04:25:12Z","timestamp":1775363112731,"version":"3.50.1"},"reference-count":61,"publisher":"Oxford University Press (OUP)","issue":"D1","license":[{"start":{"date-parts":[[2018,10,29]],"date-time":"2018-10-29T00:00:00Z","timestamp":1540771200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["1R01CA197139"],"award-info":[{"award-number":["1R01CA197139"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["1U54HG006493"],"award-info":[{"award-number":["1U54HG006493"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,1,8]]},"DOI":"10.1093\/nar\/gky1016","type":"journal-article","created":{"date-parts":[[2018,10,11]],"date-time":"2018-10-11T19:12:39Z","timestamp":1539285159000},"page":"D886-D894","source":"Crossref","is-referenced-by-count":3345,"title":["CADD: predicting the deleteriousness of variants throughout the human genome"],"prefix":"10.1093","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0413-7974","authenticated-orcid":false,"given":"Philipp","family":"Rentzsch","sequence":"first","affiliation":[{"name":"Berlin Institute of Health (BIH), 10178\u00a0Berlin, Germany"},{"name":"Charit\u00e9 - Universit\u00e4tsmedizin Berlin, 10117\u00a0Berlin, Germany"}]},{"given":"Daniela","family":"Witten","sequence":"additional","affiliation":[{"name":"Department of Statistics and Biostatistics, University of Washington, Seattle, WA 98195, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5509-9923","authenticated-orcid":false,"given":"Gregory M","family":"Cooper","sequence":"additional","affiliation":[{"name":"HudsonAlpha Institute for Biotechnology, Huntsville, AL\u00a035806, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1516-1865","authenticated-orcid":false,"given":"Jay","family":"Shendure","sequence":"additional","affiliation":[{"name":"Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA"},{"name":"Brotman Baty Institute for Precision Medicine, Seattle, WA 98195, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9278-5471","authenticated-orcid":false,"given":"Martin","family":"Kircher","sequence":"additional","affiliation":[{"name":"Berlin Institute of Health (BIH), 10178\u00a0Berlin, Germany"},{"name":"Charit\u00e9 - Universit\u00e4tsmedizin Berlin, 10117\u00a0Berlin, Germany"},{"name":"Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA"}]}],"member":"286","published-online":{"date-parts":[[2018,10,29]]},"reference":[{"key":"key\n\t\t\t\t2019012510342078900_B1","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/nature24286","article-title":"DNA sequencing at 40: past, present and future","volume":"550","author":"Shendure","year":"2017","journal-title":"Nature"},{"key":"key\n\t\t\t\t2019012510342078900_B2","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1038\/nrg3046","article-title":"Needles in stacks of needles: finding disease-causal variants in a wealth of genomic data","volume":"12","author":"Cooper","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"key\n\t\t\t\t2019012510342078900_B3","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1038\/nmeth0410-250","article-title":"Single-nucleotide evolutionary constraint scores highlight disease-causing mutations","volume":"7","author":"Cooper","year":"2010","journal-title":"Nat. Methods"},{"key":"key\n\t\t\t\t2019012510342078900_B4","doi-asserted-by":"crossref","first-page":"e1004722","DOI":"10.1371\/journal.pgen.1004722","article-title":"Integrating functional data to prioritize causal variants in statistical fine-mapping studies","volume":"10","author":"Kichaev","year":"2014","journal-title":"PLoS Genet."},{"key":"key\n\t\t\t\t2019012510342078900_B5","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/ng.2892","article-title":"A general framework for estimating the relative pathogenicity of human genetic variants","volume":"46","author":"Kircher","year":"2014","journal-title":"Nat. Genet."},{"key":"key\n\t\t\t\t2019012510342078900_B6","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1101\/gr.8.3.186","article-title":"Base-calling of automated sequencer traces using phred. II. Error probabilities","volume":"8","author":"Ewing","year":"1998","journal-title":"Genome Res."},{"key":"key\n\t\t\t\t2019012510342078900_B7","doi-asserted-by":"crossref","first-page":"D980","DOI":"10.1093\/nar\/gkt1113","article-title":"ClinVar: public archive of relationships among sequence variation and human phenotype","volume":"42","author":"Landrum","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"key\n\t\t\t\t2019012510342078900_B8","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/nature19057","article-title":"Analysis of protein-coding genetic variation in 60,706 humans","volume":"536","author":"Lek","year":"2016","journal-title":"Nature"},{"key":"key\n\t\t\t\t2019012510342078900_B9","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1038\/nbt.1589","article-title":"High-resolution analysis of DNA regulatory elements by synthetic saturation mutagenesis","volume":"27","author":"Patwardhan","year":"2009","journal-title":"Nat. Biotechnol."},{"key":"key\n\t\t\t\t2019012510342078900_B10","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/nbt.2136","article-title":"Massively parallel functional dissection of mammalian enhancers in vivo","volume":"30","author":"Patwardhan","year":"2012","journal-title":"Nat. Biotechnol."},{"key":"key\n\t\t\t\t2019012510342078900_B11","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.cels.2017.11.003","article-title":"Quantitative missense variant effect prediction using Large-Scale mutagenesis data","volume":"6","author":"Gray","year":"2018","journal-title":"Cell Syst."},{"key":"key\n\t\t\t\t2019012510342078900_B12","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/s41586-018-0461-z","article-title":"Accurate classification of BRCA1 variants with saturation genome editing","volume":"562","author":"Findlay","year":"2018","journal-title":"Nature"},{"key":"key\n\t\t\t\t2019012510342078900_B13","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1002\/humu.23035","article-title":"TP53 variations in human cancers: New lessons from the IARC TP53 database and genomics data","volume":"37","author":"Bouaoun","year":"2016","journal-title":"Hum. Mutat."},{"key":"key\n\t\t\t\t2019012510342078900_B14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/database\/baw053","article-title":"Ensembl comparative genomics resources","volume":"2016","author":"Herrero","year":"2016","journal-title":"Database"},{"key":"key\n\t\t\t\t2019012510342078900_B15","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s13059-016-0974-4","article-title":"The ensembl variant effect predictor","volume":"17","author":"McLaren","year":"2016","journal-title":"Genome Biol."},{"key":"key\n\t\t\t\t2019012510342078900_B16","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1101\/gr.097857.109","article-title":"Detection of nonneutral substitution rates on mammalian phylogenies","volume":"20","author":"Pollard","year":"2010","journal-title":"Genome Res."},{"key":"key\n\t\t\t\t2019012510342078900_B17","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1101\/gr.3715005","article-title":"Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes","volume":"15","author":"Siepel","year":"2005","journal-title":"Genome Res."},{"key":"key\n\t\t\t\t2019012510342078900_B18","doi-asserted-by":"crossref","first-page":"e1001025","DOI":"10.1371\/journal.pcbi.1001025","article-title":"Identifying a high fraction of the human genome to be under selective constraint using GERP++","volume":"6","author":"Davydov","year":"2010","journal-title":"PLoS Comput. Biol."},{"key":"key\n\t\t\t\t2019012510342078900_B19","doi-asserted-by":"crossref","first-page":"D762","DOI":"10.1093\/nar\/gkx1020","article-title":"The UCSC Genome Browser database: 2018 update","volume":"46","author":"Casper","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"key\n\t\t\t\t2019012510342078900_B20","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1126\/science.185.4154.862","article-title":"Amino acid difference formula to help explain protein evolution","volume":"185","author":"Grantham","year":"1974","journal-title":"Science"},{"key":"key\n\t\t\t\t2019012510342078900_B21","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":"key\n\t\t\t\t2019012510342078900_B22","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nmeth0410-248","article-title":"A method and server for predicting damaging missense mutations","volume":"7","author":"Adzhubei","year":"2010","journal-title":"Nat. Methods"},{"key":"key\n\t\t\t\t2019012510342078900_B23","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s13059-016-1141-7","article-title":"GAVIN: Gene-Aware Variant INterpretation for medical sequencing","volume":"18","author":"van\u00a0der\u00a0Velde","year":"2017","journal-title":"Genome Biol."},{"key":"key\n\t\t\t\t2019012510342078900_B24","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1038\/nmeth.3739","article-title":"The mutation significance cutoff: gene-level thresholds for variant predictions","volume":"13","author":"Itan","year":"2016","journal-title":"Nat. Methods"},{"key":"key\n\t\t\t\t2019012510342078900_B25","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1002\/humu.22798","article-title":"Evaluation of CADD scores in curated mismatch repair gene variants yields a model for clinical validation and prioritization","volume":"36","author":"van\u00a0der\u00a0Velde","year":"2015","journal-title":"Hum. Mutat."},{"key":"key\n\t\t\t\t2019012510342078900_B26","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/j.ajhg.2016.07.005","article-title":"A Whole-Genome analysis framework for effective identification of pathogenic regulatory variants in mendelian disease","volume":"99","author":"Smedley","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"key\n\t\t\t\t2019012510342078900_B27","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s13073-017-0433-1","article-title":"Genomic diagnosis for children with intellectual disability and\/or developmental delay","volume":"9","author":"Bowling","year":"2017","journal-title":"Genome Med."},{"key":"key\n\t\t\t\t2019012510342078900_B28","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1038\/ejhg.2017.87","article-title":"Characterization of pathogenic SORL1 genetic variants for association with Alzheimer's disease: a clinical interpretation strategy","volume":"25","author":"Holstege","year":"2017","journal-title":"Eur. J. Hum. Genet."},{"key":"key\n\t\t\t\t2019012510342078900_B29","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1038\/s41467-017-01261-5","article-title":"Functional mapping and annotation of genetic associations with FUMA","volume":"8","author":"Watanabe","year":"2017","journal-title":"Nat. Commun."},{"key":"key\n\t\t\t\t2019012510342078900_B30","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1186\/s12862-017-1018-8","article-title":"Using the Neandertal genome to study the evolution of small insertions and deletions in modern humans","volume":"17","author":"Chintalapati","year":"2017","journal-title":"BMC Evol. Biol."},{"key":"key\n\t\t\t\t2019012510342078900_B31","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1016\/j.cell.2017.01.038","article-title":"Impacts of Neanderthal-Introgressed sequences on the landscape of human gene expression","volume":"168","author":"McCoy","year":"2017","journal-title":"Cell"},{"key":"key\n\t\t\t\t2019012510342078900_B32","doi-asserted-by":"crossref","first-page":"1916","DOI":"10.1093\/molbev\/msy094","article-title":"Demographic history and genetic adaptation in the himalayan region inferred from Genome-Wide SNP genotypes of 49 populations","volume":"35","author":"Arciero","year":"2018","journal-title":"Mol. Biol. Evol."},{"key":"key\n\t\t\t\t2019012510342078900_B33","doi-asserted-by":"crossref","first-page":"e1004697","DOI":"10.1371\/journal.pgen.1004697","article-title":"Approximation to the distribution of fitness effects across functional categories in human segregating polymorphisms","volume":"10","author":"Racimo","year":"2014","journal-title":"PLos Genet."},{"key":"key\n\t\t\t\t2019012510342078900_B34","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1093\/bioinformatics\/btu703","article-title":"DANN: a deep learning approach for annotating the pathogenicity of genetic variants","volume":"31","author":"Quang","year":"2015","journal-title":"Bioinformatics"},{"key":"key\n\t\t\t\t2019012510342078900_B35","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1186\/s12859-018-2337-5","article-title":"Predicting variant deleteriousness in non-human species: applying the CADD approach in mouse","volume":"19","author":"Gro\u00df","year":"2018","journal-title":"BMC Bioinformatics"},{"key":"key\n\t\t\t\t2019012510342078900_B36","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1038\/s41588-018-0167-z","article-title":"Predicting the clinical impact of human mutation with deep neural networks","volume":"50","author":"Sundaram","year":"2018","journal-title":"Nat. Genet."},{"key":"key\n\t\t\t\t2019012510342078900_B37","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1093\/bioinformatics\/btw789","article-title":"SVScore: an impact prediction tool for structural variation","volume":"33","author":"Ganel","year":"2017","journal-title":"Bioinformatics"},{"key":"key\n\t\t\t\t2019012510342078900_B38","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.ajhg.2016.08.016","article-title":"REVEL: an ensemble method for predicting the pathogenicity of rare missense variants","volume":"99","author":"Ioannidis","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"key\n\t\t\t\t2019012510342078900_B39","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1038\/ng.3703","article-title":"M-CAP eliminates a majority of variants of uncertain significance in clinical exomes at high sensitivity","volume":"48","author":"Jagadeesh","year":"2016","journal-title":"Nat. Genet."},{"key":"key\n\t\t\t\t2019012510342078900_B40","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1186\/s13059-017-1353-5","article-title":"Evaluation of in silico algorithms for use with ACMG\/AMP clinical variant interpretation guidelines","volume":"18","author":"Ghosh","year":"2017","journal-title":"Genome Biol."},{"key":"key\n\t\t\t\t2019012510342078900_B41","first-page":"e13","article-title":"IMHOTEP\u2014a composite score integrating popular tools for predicting the functional consequences of non-synonymous sequence variants","volume":"45","author":"Knecht","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"key\n\t\t\t\t2019012510342078900_B42","first-page":"2157","article-title":"Optimized cutting plane algorithm for Large-Scale risk minimization","volume":"10","author":"Franc","year":"2009","journal-title":"J. Mach. Learn. Res."},{"key":"key\n\t\t\t\t2019012510342078900_B43","doi-asserted-by":"crossref","first-page":"716","DOI":"10.14778\/2212351.2212354","article-title":"Distributed GraphLab: A framework for machine learning and data mining in the cloud","volume":"5","author":"Low","year":"2012","journal-title":"Proc. VLDB Endow."},{"key":"key\n\t\t\t\t2019012510342078900_B44","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1109\/MCSE.2007.58","article-title":"Python for scientific computing","volume":"9","author":"Oliphant","year":"2007","journal-title":"Comput. Sci. Engin."},{"key":"key\n\t\t\t\t2019012510342078900_B45","first-page":"2825","article-title":"Scikit-learn: Machine learning in python","volume":"12","author":"Pedregosa","year":"2011","journal-title":"J. Mach. Learn. Res."},{"key":"key\n\t\t\t\t2019012510342078900_B46","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1093\/bioinformatics\/btq671","article-title":"Tabix: fast retrieval of sequence features from generic TAB-delimited files","volume":"27","author":"Li","year":"2011","journal-title":"Bioinformatics"},{"key":"key\n\t\t\t\t2019012510342078900_B47","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1093\/database\/bax020","article-title":"Ensembl core software resources: storage and programmatic access for DNA sequence and genome annotation","volume":"2017","author":"Ruffier","year":"2017","journal-title":"Database (Oxford)"},{"key":"key\n\t\t\t\t2019012510342078900_B48","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1002\/humu.22932","article-title":"dbNSFP v3.0: A One-Stop database of functional predictions and annotations for human nonsynonymous and Splice-Site SNVs","volume":"37","author":"Liu","year":"2016","journal-title":"Hum. Mutat."},{"key":"key\n\t\t\t\t2019012510342078900_B49","doi-asserted-by":"crossref","first-page":"e164","DOI":"10.1093\/nar\/gkq603","article-title":"ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data","volume":"38","author":"Wang","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"key\n\t\t\t\t2019012510342078900_B50","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1038\/nature08250","article-title":"Targeted capture and massively parallel sequencing of 12 human exomes","volume":"461","author":"Ng","year":"2009","journal-title":"Nature"},{"key":"key\n\t\t\t\t2019012510342078900_B51","doi-asserted-by":"crossref","DOI":"10.1093\/bioinformatics\/bty536","article-title":"PopViz: a webserver for visualizing minor allele frequencies and damage prediction scores of human genetic variations","author":"Zhang","year":"2018","journal-title":"Bioinformatics"},{"key":"key\n\t\t\t\t2019012510342078900_B52","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1038\/ng.3331","article-title":"A method to predict the impact of regulatory variants from DNA sequence","volume":"47","author":"Lee","year":"2015","journal-title":"Nat. Genet."},{"key":"key\n\t\t\t\t2019012510342078900_B53","doi-asserted-by":"crossref","first-page":"1254806","DOI":"10.1126\/science.1254806","article-title":"RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease","volume":"347","author":"Xiong","year":"2015","journal-title":"Science"},{"key":"key\n\t\t\t\t2019012510342078900_B54","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1038\/nmeth.3547","article-title":"Predicting effects of noncoding variants with deep learning-based sequence model","volume":"12","author":"Zhou","year":"2015","journal-title":"Nat. Meth."},{"key":"key\n\t\t\t\t2019012510342078900_B55","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1038\/s41588-018-0160-6","article-title":"Deep learning sequence-based ab initio prediction of variant effects on expression and disease risk","volume":"50","author":"Zhou","year":"2018","journal-title":"Nat. Genet."},{"key":"key\n\t\t\t\t2019012510342078900_B56","doi-asserted-by":"crossref","first-page":"2024","DOI":"10.1101\/gr.224964.117","article-title":"Deep learning of the regulatory grammar of yeast 5\u2032 untranslated regions from 500,000 random sequences","volume":"27","author":"Cuperus","year":"2017","journal-title":"Genome Res."},{"key":"key\n\t\t\t\t2019012510342078900_B57","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.ajhg.2017.07.014","article-title":"Variant interpretation: functional assays to the rescue","volume":"101","author":"Starita","year":"2017","journal-title":"Am. J. Hum. Genet."},{"key":"key\n\t\t\t\t2019012510342078900_B58","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1002\/humu.10212","article-title":"Human gene mutation database (HGMD): 2003 update","volume":"21","author":"Stenson","year":"2003","journal-title":"Hum. Mutat."},{"key":"key\n\t\t\t\t2019012510342078900_B59","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1038\/ng.3477","article-title":"A spectral approach integrating functional genomic annotations for coding and noncoding variants","volume":"48","author":"Ionita-Laza","year":"2016","journal-title":"Nat. Genet."},{"key":"key\n\t\t\t\t2019012510342078900_B60","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1038\/ng.3810","article-title":"Fast, scalable prediction of deleterious noncoding variants from functional and population genomic data","volume":"49","author":"Huang","year":"2017","journal-title":"Nat. Genet."},{"key":"key\n\t\t\t\t2019012510342078900_B61","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/s41588-018-0062-7","article-title":"The human noncoding genome defined by genetic diversity","volume":"50","author":"Iulio","year":"2018","journal-title":"Nat. Genet."}],"container-title":["Nucleic Acids Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/nar\/article-pdf\/47\/D1\/D886\/27436395\/gky1016.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T22:36:41Z","timestamp":1693953401000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/nar\/article\/47\/D1\/D886\/5146191"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,29]]},"references-count":61,"journal-issue":{"issue":"D1","published-online":{"date-parts":[[2018,10,29]]},"published-print":{"date-parts":[[2019,1,8]]}},"URL":"https:\/\/doi.org\/10.1093\/nar\/gky1016","relation":{},"ISSN":["0305-1048","1362-4962"],"issn-type":[{"value":"0305-1048","type":"print"},{"value":"1362-4962","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,1,8]]},"published":{"date-parts":[[2018,10,29]]}}}