A secure system for genomics clinical decision support

Masys, 2012, Technical desiderata for the integration of genomic data into Electronic Health Records, J. Biomed. Inform., 45, 419, 10.1016/j.jbi.2011.12.005 Starren, 2013, Crossing the omic chasm: a time for omic ancillary systems, JAMA, 309, 1237, 10.1001/jama.2013.1579 Honeyman, 1994, Picture archiving and communications systems (PACS), Curr. Probl. Diagn. Radiol., 23, 101, 10.1016/0363-0188(94)90004-3 National Institute of Standards and Technology, NIST Cloud Computing Program - NCCP, Nov. 15, 2010. https://www.nist.gov/programs-projects/nist-cloud-computing-program-nccp (accessed Apr. 30, 2020). Lippert, 2017, Identification of individuals by trait prediction using whole-genome sequencing data, Proc. Natl. Acad. Sci., 114, 10166, 10.1073/pnas.1711125114 National Institute of Standards and Technology, NVD - Control - SC-28 - Protection of Information at Rest. https://nvd.nist.gov/800-53/Rev4/control/SC-28 (accessed Apr. 29, 2020). Office for Civil Rights (OCR), The Security Rule. US Department of Health and Human Services, 2017. Yao, 1986, How to generate and exchange secrets, 162 Pinkas, 2009, Secure Two-Party Computation Is Practical, Advances in Cryptology – ASIACRYPT 2009, 250, 10.1007/978-3-642-10366-7_15 Bellare, 2012, Foundations of garbled circuits, Proceedings of the 2012 ACM Conference on Computer and Communications Security, 784, 10.1145/2382196.2382279 Ben-Or, 1988, Completeness theorems for non-cryptographic fault-tolerant distributed computation, 1 Cho, 2018, Secure genome-wide association analysis using multiparty computation, Nat. Biotechnol., 36, 547, 10.1038/nbt.4108 Damgaard, 2012, Multiparty Computation from Somewhat Homomorphic Encryption, Advances in Cryptology – CRYPTO 2012, 643, 10.1007/978-3-642-32009-5_38 Jagadeesh, 2017, Deriving genomic diagnoses without revealing patient genomes, Science, 357, 692, 10.1126/science.aam9710 Aziz, 2017, Privacy-preserving techniques of genomic data—a survey, Brief. Bioinform., 20, 887, 10.1093/bib/bbx139 Chen, 2017, Princess: Privacy-protecting rare disease international network collaboration via encryption through software guard extensions, Bioinformatics, 33, 871, 10.1093/bioinformatics/btw758 Chen, 2017, PRESAGE: privacy-preserving genetic testing via software guard extension, BMC Med. Genomics, 10, 48 Sadat, 2018, SAFETY: Secure gwAs in Federated Environment Through a hYbrid solution Wang, 2016, HEALER: homomorphic computation of ExAct Logistic rEgRession for secure rare disease variants analysis in GWAS, Bioinformatics, 32, 211, 10.1093/bioinformatics/btv563 Zhang, 2015, Foresee: Fully outsourced secure genome study based on homomorphic encryption, BMC Med. Informat. Decision Making, 15, S5, 10.1186/1472-6947-15-S5-S5 Schuster, 2015, VC3: trustworthy data analytics in the cloud using SGX, 38 A. Moghimi, T. Eisenbarth, B. Sunar, MemJam: A false dependency attack against constant-time crypto implementations in SGX, in: Topics in Cryptology – CT-RSA 2018, 2018, pp. 21–44. Evtyushkin, 2018, A New Side-Channel Attack on Directional Branch Predictor, SIGPLAN Not, 53, 693, 10.1145/3296957.3173204 CryptoExperts, Post-Quantum Cryptography. https://www.cryptoexperts.com/services/post_quantum_cryptography/ (accessed Apr. 29, 2020). Gentry, 2009, Fully homomorphic encryption using ideal lattices, 169 Wang, 2018, iDASH secure genome analysis competition 2017, BMC Med. Genomics, 11, 85, 10.1186/s12920-018-0396-0 Rasmussen, 2020, The genomic medical record and omic ancillary systems, 253 Walton, 2019, Genomic data in the electronic health record, Adv. Mol. Pathol., 2, 21, 10.1016/j.yamp.2019.07.001 Williams, 2019, Genomic information for clinicians in the electronic health record: lessons learned from the clinical genome resource project and the electronic medical records and genomics network, Front. Genet., 10, 10.3389/fgene.2019.01059 “Sync for Genes | HealthIT.gov.” https://www.healthit.gov/topic/sync-genes (accessed Jul. 24, 2020). Dolin, 2018, A pharmacogenomics clinical decision support service based on FHIR and CDS Hooks, Methods, Inf. Med., 57 Bell, 2014, Development and use of active clinical decision support for preemptive pharmacogenomics, J. Am. Med. Inform. Assoc. JAMIA, 21, e93, 10.1136/amiajnl-2013-001993 Relling, 2015, Pharmacogenomics in the clinic, Nature, 526, 343, 10.1038/nature15817 Van Driest, 2014, Clinically actionable genotypes among 10,000 patients with preemptive pharmacogenomic testing, Clin. Pharmacol. Ther., 95, 423, 10.1038/clpt.2013.229 “Clopidogrel Bisulfate - Drug Usage Statistics, ClinCalc DrugStats Database.” https://clincalc.com/DrugStats/Drugs/ClopidogrelBisulfate (accessed Apr. 28, 2020). “CPIC® Guideline for Clopidogrel and CYP2C19.” https://cpicpgx.org/guidelines/guideline-for-clopidogrel-and-cyp2c19/ (accessed Apr. 28, 2020). Kalia, 2017, Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics, Genet. Med. Off. J. Am. Coll. Med. Genet., 19, 249 Dorschner, 2013, Actionable, pathogenic incidental findings in 1,000 participants’ exomes, Am. J. Hum. Genet., 93, 10.1016/j.ajhg.2013.08.006 Jang, 2015, Frequency and spectrum of actionable pathogenic secondary findings in 196 Korean exomes, Genet. Med. Off. J. Am. Coll. Med. Genet., 17 Thompson, 2018, Genomic sequencing identifies secondary findings in a cohort of parent study participants, Genet. Med. Off. J. Am. Coll. Med. Genet., 20 Landrum, 2016, ClinVar: public archive of interpretations of clinically relevant variants, Nucleic Acids Res., 44, 10.1093/nar/gkv1222 National Center for Biotechnology Information, NCBI ClinVar gene-specific summary, 2018, National Institutes of Health (NIH), ftp://ftp.ncbi.nlm.nih.gov/pub/clinvar/tab_delimited/archive/2018/gene_specific_summary_2018-01.txt.gz (accessed Apr. 28, 2020). Akioyamen, 2017, Estimating the prevalence of heterozygous familial hypercholesterolaemia: a systematic review and meta-analysis, BMJ Open, 7, 10.1136/bmjopen-2017-016461 de Ferranti, 2016, Prevalence of familial hypercholesterolemia in the 1999 to 2012 United States National Health and Nutrition Examination Surveys (NHANES), Circulation, 133, 10.1161/CIRCULATIONAHA.115.018791 Rehm, 2015, ClinGen–the clinical genome resource, N. Engl. J. Med., 372, 10.1056/NEJMsr1406261 US National Library of Medicine, A Study of CNP520 Versus Placebo in Participants at Risk for the Onset of Clinical Symptoms of Alzheimer’s Disease. https://clinicaltrials.gov/ct2/show/NCT03131453 (accessed Apr. 28, 2020). Reilly, 1998, Genetic risk assessment and insurance, Genet. Test., 2, 1, 10.1089/gte.1998.2.1 Naveed, 2015, Privacy in the genomic era, ACM Comput. Surv., 48, 10.1145/2767007 Molteni, 2018, The creepy genetics behind the golden state killer case, Wired Lin, 2004, Genomic research and human subject privacy, Science, 305, 10.1126/science.1095019 Shringarpure, 2015, Privacy risks from genomic data-sharing beacons, Am. J. Hum. Genet., 97, 631, 10.1016/j.ajhg.2015.09.010 Raisaro, 2017, Addressing Beacon re-identification attacks: quantification and mitigation of privacy risks, J. Am. Med. Inform. Assoc. JAMIA, 24, 799, 10.1093/jamia/ocw167 von Thenen, 2019, Re-identification of individuals in genomic data-sharing beacons via allele inference, Bioinformatics, 35, 365, 10.1093/bioinformatics/bty643 Harmanci, 2016, Quantification of private information leakage from phenotype-genotype data: linking attacks, Nat. Methods, 13, 251, 10.1038/nmeth.3746 Carter, 2019, Considerations for genomic data privacy and security when working in the cloud, J. Mol. Diagn. JMD, 21, 542, 10.1016/j.jmoldx.2018.07.009 Jiang, 2014, A community assessment of privacy preserving techniques for human genomes, BMC Med. Inform. Decis. Mak., 14, S1, 10.1186/1472-6947-14-S1-S1 Shimizu, 2016, Efficient privacy-preserving string search and an application in genomics, Bioinformatics, 32, 1652, 10.1093/bioinformatics/btw050 Kim, 2017, Secure searching of biomarkers through hybrid homomorphic encryption scheme, BMC Med. Genomics, 10, 42, 10.1186/s12920-017-0280-3 M. Kim, Y. Song, B. Li, D. Micciancio, Semi-parallel Logistic Regression for GWAS on Encrypted Data, 294, 2019. [Online]. Available: http://eprint.iacr.org/2019/294 (accessed: May 11, 2020). The Variant Call Format Specification. [Online]. Available: https://samtools.github.io/hts-specs/VCFv4.3.pdf (accessed: May 01, 2020). Cheon, 2017, Homomorphic encryption for arithmetic of approximate numbers, Lect. Notes Comput. Sci., 409, 10.1007/978-3-319-70694-8_15 Brakerski, 2012, Fully Homomorphic Encryption without Modulus Switching from Classical GapSVP, Lect. Notes Comput. Sci., 868, 10.1007/978-3-642-32009-5_50 J. Fan, F. Vercauteren, Somewhat Practical Fully Homomorphic Encryption, 144, 2012. [Online]. Available: https://eprint.iacr.org/2012/144 (accessed: May 08, 2020). W. Jakob, J. Rhinelander, and D. Moldovan, “pybind11 — Seamless operability between C++11 and Python,” 2016. https://rgl.epfl.ch/software/pybind11 (accessed Apr. 28, 2020). Whirl-Carrillo, 2012, Pharmacogenomics Knowledge for Personalized Medicine, Clinical Pharmacology & Therapeutics, 92, 414, 10.1038/clpt.2012.96 1000 Genomes Project Consortium et al., A global reference for human genetic variation, Nature 526(7571) (2015). doi: 10.1038/nature15393. Art. no. 7571. Li, 2011, Tabix: fast retrieval of sequence features from generic TAB-delimited files, Bioinformatics, 27, 718, 10.1093/bioinformatics/btq671 “NCBI Variation Services.” https://api.ncbi.nlm.nih.gov/variation/v0/ (accessed Apr. 28, 2020). M. Albrecht et al., Homomorphic Encryption Security Standard, HomomorphicEncryption.org, Toronto, Canada, Nov. 2018. [Online]. Available: https://homomorphicencryption.org/standard/ (accessed: Jul. 24, 2019).