{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T06:36:47Z","timestamp":1725518207434},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,1,15]]},"abstract":"Abstract<\/jats:title>\n Motivation: Genome-wide association studies (GWAS) have been widely used in discovering the association between genotypes and phenotypes. Human genome data contain valuable but highly sensitive information. Unprotected disclosure of such information might put individual\u2019s privacy at risk. It is important to protect human genome data. Exact logistic regression is a bias-reduction method based on a penalized likelihood to discover rare variants that are associated with disease susceptibility. We propose the HEALER framework to facilitate secure rare variants analysis with a small sample size.<\/jats:p>\n Results: We target at the algorithm design aiming at reducing the computational and storage costs to learn a homomorphic exact logistic regression model (i.e. evaluate P-values of coefficients), where the circuit depth is proportional to the logarithmic scale of data size. We evaluate the algorithm performance using rare Kawasaki Disease datasets.<\/jats:p>\n Availability and implementation: Download HEALER at http:\/\/research.ucsd-dbmi.org\/HEALER\/<\/jats:p>\n Contact: \u00a0shw070@ucsd.edu<\/jats:p>\n Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btv563","type":"journal-article","created":{"date-parts":[[2015,10,8]],"date-time":"2015-10-08T01:29:10Z","timestamp":1444267750000},"page":"211-218","source":"Crossref","is-referenced-by-count":72,"title":["HEALER: homomorphic computation of ExAct Logistic rEgRession for secure rare disease variants analysis in GWAS"],"prefix":"10.1093","volume":"32","author":[{"given":"Shuang","family":"Wang","sequence":"first","affiliation":[{"name":"1 Department of Biomedical Informatics, University of California, San Diego, CA 92093,"}]},{"given":"Yuchen","family":"Zhang","sequence":"additional","affiliation":[{"name":"1 Department of Biomedical Informatics, University of California, San Diego, CA 92093,"},{"name":"2 Department of Electronic Engineering, Shanghai Jiao Tong University, Shanghai 200240, China,"}]},{"given":"Wenrui","family":"Dai","sequence":"additional","affiliation":[{"name":"1 Department of Biomedical Informatics, University of California, San Diego, CA 92093,"},{"name":"2 Department of Electronic Engineering, Shanghai Jiao Tong University, Shanghai 200240, China,"}]},{"given":"Kristin","family":"Lauter","sequence":"additional","affiliation":[{"name":"3 Microsoft Research, San Diego, CA 92122, USA,"}]},{"given":"Miran","family":"Kim","sequence":"additional","affiliation":[{"name":"4 Seoul National University, Seoul, 151-742, Republic of Korea and"}]},{"given":"Yuzhe","family":"Tang","sequence":"additional","affiliation":[{"name":"5 Department of Electrical Engineering and Computer Science, Syracuse University, Syracuse, NY 13244, USA"}]},{"given":"Hongkai","family":"Xiong","sequence":"additional","affiliation":[{"name":"2 Department of Electronic Engineering, Shanghai Jiao Tong University, Shanghai 200240, China,"}]},{"given":"Xiaoqian","family":"Jiang","sequence":"additional","affiliation":[{"name":"1 Department of Biomedical Informatics, University of California, San Diego, CA 92093,"}]}],"member":"286","published-online":{"date-parts":[[2015,10,6]]},"reference":[{"key":"2023020110255996200_btv563-B1","article-title":"Privacy-preserving computation of disease risk by using genomic, clinical, and environmental data","volume-title":"Proceedings of USENIX Security Workshop on Health Information Technologies (HealthTech\u201d 13)","author":"Ayday","year":"2013"},{"key":"2023020110255996200_btv563-B2","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1145\/1151690.1151692","article-title":"Energy-aware lossless data compression","volume":"24","author":"Barr","year":"2006","journal-title":"ACM Trans. Comput. Syst."},{"key":"2023020110255996200_btv563-B3","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1613\/jair.1491","article-title":"On prediction using variable order Markov models","volume":"22","author":"Begleiter","year":"2004","journal-title":"J. Artif. Intell. Res."},{"key":"2023020110255996200_btv563-B4","volume-title":"Pattern Recognition and Machine Learning Springer","author":"Bishop","year":"2006"},{"key":"2023020110255996200_btv563-B5","first-page":"1","article-title":"Fast variants of RSA","volume":"5","author":"Boneh","year":"2002","journal-title":"CryptoBytes"},{"key":"2023020110255996200_btv563-B6","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.jbi.2014.04.003","article-title":"Private predictive analysis on encrypted medical data","volume":"50","author":"Bos","year":"2014","journal-title":"J. Biomed. Inform."},{"key":"2023020110255996200_btv563-B7","doi-asserted-by":"crossref","DOI":"10.1145\/2090236.2090262","article-title":"(Leveled) fully homomorphic encryption without bootstrapping","author":"Brakerski","year":"2012"},{"key":"2023020110255996200_btv563-B8","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1137\/120868669","article-title":"Efficient fully homomorphic encryption from (standard) LWE","volume":"43","author":"Brakerski","year":"2011","journal-title":"SIAM J. Comput."},{"key":"2023020110255996200_btv563-B9","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.ajhg.2009.11.017","article-title":"Prioritizing GWAS results: a review of statistical methods and recommendations for their application","volume":"86","author":"Cantor","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"2023020110255996200_btv563-B10","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/519400a","article-title":"Cloud cover protects gene data","volume":"519","author":"Check Hayden","year":"2015","journal-title":"Nature"},{"key":"2023020110255996200_btv563-B11","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-662-48051-9_15","article-title":"Homomorphic Computation of Edit Distance","volume-title":"WAHC\u201915 - 3rd Workshop on Encrypted Computing and Applied Homomorphic Cryptography","author":"Cheon","year":"2015"},{"key":"2023020110255996200_btv563-B12","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nrg2779","article-title":"Uncovering the roles of rare variants in common disease through whole-genome sequencing","volume":"11","author":"Cirulli","year":"2010","journal-title":"Nat. Rev. Genet."},{"key":"2023020110255996200_btv563-B13","author":"Deutsch","year":"1996"},{"key":"2023020110255996200_btv563-B14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-540-79228-4_1","article-title":"Differential privacy: a survey of results","volume-title":"Theory and Applications of Models of Computation","author":"Dwork","year":"2008"},{"key":"2023020110255996200_btv563-B15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2007\/13801","article-title":"A survey of homomorphic encryption for nonspecialists","volume":"2007","author":"Fontaine","year":"2007","journal-title":"EURASIP J. Inf. Secur."},{"key":"2023020110255996200_btv563-B16","first-page":"129","article-title":"Implementing gentry\u2019s fully-homomorphic encryption scheme","volume-title":"Advances in Cryptology\u2013EUROCRYPT","author":"Gentry","year":"2011"},{"key":"2023020110255996200_btv563-B17","first-page":"150","article-title":"A new security proof for Damgard\u2019s ElGamal","volume":"vol. 3860","author":"Gj\u00f8steen","year":"2006","journal-title":"Topics in Cryptology \u2013 CT-RSA."},{"key":"2023020110255996200_btv563-B18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-642-37682-5_1","article-title":"ML confidential: machine learning on encrypted data","volume-title":"Information Security and Cryptology\u2013ICISC 2012","author":"Graepel","year":"2013"},{"key":"2023020110255996200_btv563-B19","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1126\/science.1229566","article-title":"Identifying personal genomes by surname inference","volume":"339","author":"Gymrek","year":"2013","journal-title":"Science"},{"key":"2023020110255996200_btv563-B20","doi-asserted-by":"crossref","first-page":"e1003419","DOI":"10.1371\/journal.pgen.1003419","article-title":"Genome-wide testing of putative functional exonic variants in relationship with breast and prostate cancer risk in a multiethnic population","volume":"9","author":"Haiman","year":"2013","journal-title":"PLoS Genet."},{"key":"2023020110255996200_btv563-B21","doi-asserted-by":"crossref","first-page":"D514","DOI":"10.1093\/nar\/gki033","article-title":"Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders","volume":"33","author":"Hamosh","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"2023020110255996200_btv563-B22","first-page":"851","article-title":"Wald\u2019s test as applied to hypotheses in logit analysis","volume":"72","author":"Hauck","year":"1977","journal-title":"J. Am. Stat. Assoc."},{"key":"2023020110255996200_btv563-B23","doi-asserted-by":"crossref","first-page":"e1000167","DOI":"10.1371\/journal.pgen.1000167","article-title":"Resolving individuals contributing trace amounts of DNA to highly complex mixtures using high-density SNP genotyping microarrays","volume":"4","author":"Homer","year":"2008","journal-title":"PLoS Genet."},{"key":"2023020110255996200_btv563-B24","doi-asserted-by":"crossref","DOI":"10.1145\/2508859.2516707","article-title":"Addressing the concerns of the lacks family: Quantification of kin genomic privacy","author":"Humbert","year":"2013"},{"key":"2023020110255996200_btv563-B25","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1002\/humu.22587","article-title":"Reducing false-positive incidental findings with ensemble genotyping and logistic regression based variant filtering methods","volume":"35","author":"Hwang","year":"2014","journal-title":"Hum. Mutat."},{"key":"2023020110255996200_btv563-B26","first-page":"S1","article-title":"A community assessment of privacy preserving techniques on human genome data","volume":"14","author":"Jiang","year":"2014","journal-title":"BMC"},{"key":"2023020110255996200_btv563-B27","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1093\/bioinformatics\/btt066","article-title":"A new way to protect privacy in large-scale genome-wide association studies","volume":"29","author":"Kamm","year":"2013","journal-title":"Bioinformatics"},{"key":"2023020110255996200_btv563-B28","article-title":"Private computation on encrypted genomic data","author":"Lauter","year":"2014"},{"key":"2023020110255996200_btv563-B29","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1126\/science.1095019","article-title":"Genomic research and human subject privacy","volume":"305","author":"Lin","year":"2004","journal-title":"Science"},{"key":"2023020110255996200_btv563-B30","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1016\/j.ajhg.2013.11.005","article-title":"Whole-exome sequencing of 2\u2009000 Danish individuals and the role of rare coding variants in type 2 diabetes","volume":"93","author":"Lohmueller","year":"2013","journal-title":"Am. J. Hum. Genet."},{"key":"2023020110255996200_btv563-B31","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.jbi.2004.04.005","article-title":"How (not) to protect genomic data privacy in a distributed network: using trail re-identification to evaluate and design anonymity protection systems","volume":"37","author":"Malin","year":"2004","journal-title":"J. Biomed. Inform."},{"key":"2023020110255996200_btv563-B32","doi-asserted-by":"crossref","DOI":"10.1142\/9789812799623_0005","article-title":"Inferring genotype from clinical phenotype through a knowledge based algorithm","author":"Malin","year":"2001"},{"key":"2023020110255996200_btv563-B33","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1080\/01621459.2000.10473906","article-title":"Efficient Monte Carlo Methods for Conditional Logistic Regression","volume":"95","author":"Mehta","year":"2000","journal-title":"J. Am. Stat. Assoc."},{"key":"2023020110255996200_btv563-B34","doi-asserted-by":"crossref","first-page":"2143","DOI":"10.1002\/sim.4780141908","article-title":"Exact logistic regression: Theory and examples","volume":"14","author":"Mehta","year":"1995","journal-title":"Stat. Med."},{"key":"2023020110255996200_btv563-B35","doi-asserted-by":"crossref","DOI":"10.1145\/2046660.2046682","article-title":"Can homomorphic encryption be practical?","author":"Naehrig","year":"2011"},{"key":"2023020110255996200_btv563-B36","first-page":"1","article-title":"Privacy and Security in the Genomic Era","volume":"1405.1891v","author":"Naveed","year":"2014","journal-title":"arXiv"},{"key":"2023020110255996200_btv563-B37","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/gm432","article-title":"Low concordance of multiple variant-calling pipelines: practical implications for exome and genome sequencing","volume":"5","author":"O\u2019Rawe","year":"2013","journal-title":"Genome med"},{"key":"2023020110255996200_btv563-B38","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1136\/amiajnl-2011-000538","article-title":"iDASH. Integrating data for analysis, anonymization, and sharing","volume":"19","author":"Ohno-Machado","year":"2012","journal-title":"J. Am. Med. Informatics Assoc."},{"key":"2023020110255996200_btv563-B39","doi-asserted-by":"crossref","DOI":"10.1007\/3-540-48910-X_16","article-title":"Public-key cryptosystems based on composite degree residuosity classes","volume-title":"Advances in Cryptology\u2014EUROCRYPT\u201999","author":"Paillier","year":"1999"},{"key":"2023020110255996200_btv563-B40","author":"Pavlov","year":"2007"},{"key":"2023020110255996200_btv563-B41","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1038\/ng.952","article-title":"Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease","volume":"43","author":"Rivas","year":"2011","journal-title":"Nat. Genet."},{"key":"2023020110255996200_btv563-B42","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-4614-9443-0","volume-title":"Design, Analysis, and Interpretation of Genome-Wide Association Scans","author":"Stram","year":"2014"},{"key":"2023020110255996200_btv563-B43","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1038\/ng.2957","article-title":"Severe osteoarthritis of the hand associates with common variants within the ALDH1A2 gene and with rare variants at 1p31","volume":"46","author":"Styrkarsdottir","year":"2014","journal-title":"Nat. Genet."},{"key":"2023020110255996200_btv563-B44","volume-title":"Identifying participants in the personal genome project by name (A Re-identification experiment). White Paper 1021\u20131","author":"Sweeney","year":"2013"},{"key":"2023020110255996200_btv563-B45","article-title":"Privacy-preserving statistical analysis by exact logistic regression","volume-title":"2nd International Workshop on Genome Privacy and Security (GenoPri\u201915)","author":"Verle","year":"2015"},{"key":"2023020110255996200_btv563-B46","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.ajhg.2011.11.029","article-title":"Five years of GWAS discovery","volume":"90","author":"Visscher","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"2023020110255996200_btv563-B47","doi-asserted-by":"crossref","DOI":"10.1145\/1653662.1653726","article-title":"Learning your identity and disease from research papers","author":"Wang","year":"2009"},{"key":"2023020110255996200_btv563-B48","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1186\/1472-6947-14-S1-S2","article-title":"Differentially private genome data dissemination through top-down specialization","volume":"14","author":"Wang","year":"2014","journal-title":"BMC Med. Inform. Decis. Mak."},{"key":"2023020110255996200_btv563-B49","doi-asserted-by":"crossref","first-page":"3334","DOI":"10.1093\/bioinformatics\/btu561","article-title":"SecureMA: protecting participant privacy in genetic association meta-analysis","volume":"30","author":"Xie","year":"2014","journal-title":"Bioinformatics"},{"key":"2023020110255996200_btv563-B50","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1186\/1472-6947-14-S1-S3","article-title":"Scalable privacy-preserving data sharing methodology for genome-wide association studies: an application to iDASH healthcare privacy protection challenge","volume":"14","author":"Yu","year":"2014","journal-title":"BMC Med. Inform. Decis. Mak."},{"key":"2023020110255996200_btv563-B51","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1136\/amiajnl-2014-003043","article-title":"Choosing blindly but wisely: differentially private solicitation of DNA datasets for disease marker discovery","volume":"22","author":"Zhao","year":"2015","journal-title":"J. Am. Med. Inform. Assoc."}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/32\/2\/211\/49016603\/bioinformatics_32_2_211.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/32\/2\/211\/49016603\/bioinformatics_32_2_211.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T21:28:24Z","timestamp":1675286904000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/32\/2\/211\/1744166"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,10,6]]},"references-count":51,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2016,1,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btv563","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2016,1,15]]},"published":{"date-parts":[[2015,10,6]]}}}