Bethesda, MD 20892 Population allele frequencies for SNPs are generally available, and so for a SNP, Consequently, we might seek an orthogonal matrix approximation, Examples of attempted decryption using FastICA, The plaintext is highly compressible (at least if all the genotypes are integral), so we might instead seek, If all the individuals in the study are from a set of known pedigrees (for example a large set of trios), then the expected plaintext GRM, This suggests another attack on the problem: find a series of, There is one clear-cut weakness to orthogonal encryption, which occurs when ultrarare private variants are present. Google Scholar. (G2P). The Database of Genotypes and Phenotypes (dbGaP) is the National Institutes of Health (NIH) sponsored repository charged to archive, curate and distribute information produced by studies investigating the interaction of genotype and phenotype. Here, we sketch various generalizations to the orthogonal encryption scheme. 36, 431432 (2004). J. Hum. This general principle could be applied more widely. Each then privately encrypts and shares their own ciphertext, and analyses all parties ciphertexts. The NCBI dbGaP database of genotypes and phenotypes. In this scheme, the values in each column of F are first ranked and then replaced by their corresponding standard normal quantiles. Larger keys of realistic size take significantly longer, e.g., when n=10,000, a single key takes 1 CPU hr to generate. 2016) for platelet counts on mouse chromosome 11, which are publicly available as described below in Supplemental Material, File S1. Sharing human genotype and phenotype data is essential to discover otherwise inaccessible genetic associations, but is a challenge because of privacy concerns. A simple solution would be to first permute the rows of D, then group them into a maximum of 1,00010,000 individuals per group, and sample an independent orthogonal key to encrypt each group separately, as described above. The automated process of extracting data from web pages intended for human viewing. The relationship between genetic variation in an organism and how this affects its observable characteristics. FastICA (Hyvrinen and Oja 1997) finds an orthogonal transformation to map the data onto interesting directions, such that the projections of the data are strongly non-Gaussian along these directions; in our case, we seek directions in which the distributions are trimodal. 31 Center Drive With HE, it is possible to build systems that store and process encrypted data, such that the data always stay encrypted both in transit and at rest. That is, two sets D1,D2 are equivalent if there exists an orthogonal matrix P such that D1(P)=D2, i.e., that maps one to the other. The current study aims to address the relationship between apolipoprotein E ( APOE ) genotype and obesity in dementia. 35, D5D12 (2007). The Database of Genotypes and Phenotypes (dbGaP) ( 1) is a National Institutes of Health (NIH)-sponsored repository charged to archive, curate and distribute information produced by studies investigating the interaction of genotype and phenotype. The syntax of information is concerned with how the data is organized, ordered and structured. To obtain Any random rotation of the genotypes produces coordinates such that the ciphertext dosages closely resemble a Gaussian sample. PhenCode: connecting ENCODE data with mutations and phenotype. Taylor, C. F. et al. Bioinform. Background While obesity in midlife is a risk factor for dementia, several studies suggested that obesity also protected against dementia, hence so-called obesity paradox. A road map for efficient and reliable human genome epidemiology. Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders. Big data: the future of biocuration. An extension of the World Wide Web that embeds semantics, or meaning, in documents, in links between documents and in descriptions of web services, thereby enabling navigation and reasoning by automated agents. (GWA study). All these methods are thought to be cryptographically secure, but they limit the types of computation and data exploration possible. dbGaP is an online repository created by the National Center for Biotechnology Information (NCBI) (Mailman et . Dissecting the genetics of complex traits using summary association statistics. Elnitski, L. L. et al. 2010; Wen and Yin 2013). Nature 435, 10101011 (2005). The encryption uses a high-dimensional random linear orthogonal transformation key that leaves the likelihood of quantitative trait data unchanged under a linear model with normally distributed errors. Nucleic Acids Res. A professional perspective. You are using a browser version with limited support for CSS. 22 July 2022, BMC Genomics Open Access articles citing this article. Encrypted ciphertext and unencrypted plaintext are analytically interchangeable. To the best of our knowledge, there is no database including the structures of mutant GLAs. In addition to genomic data, dbGaP requires investigators to submit phenotype data. The host data archive then prepares data sets, encrypted with keys that may be specific to each data request, for transfer over a public network. Benson, D. A. et al. Each row of the matrix represents one individual and each column one SNP. 1, 398414 (2000). However, the mean absolute error in the decrypted quantile-normalized standardized genotype dosages [[HPTFq]] rose to 0.03585 (i.e., mean discrepancy 18%), maximum 0.06980. Since the Genomic Data Sharing Policy was issued in 2007 (Contreras, 2015), the National Institutes of Health (NIH) has supported several repositories such as the database of Genotypes and Phenotypes (dbGaP), Genome Expression Omnibus (GEO) and the Cancer Genomics Hubs. The correlation between the logP values of the tests of association was 0.999. Tag: Database of Genotypes and Phenotypes (dbGaP) The entire corpus of the Sequence Read Archive (SRA) now live on two cloud platforms! Consequently, orthogonal permutation matrices in isolation are useless as keys. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide, This PDF is available to Subscribers Only. An international research project to identify all functional elements in the human genome. If P is truly random then we seek U given PU, which appears to be hard problem, since PU resembles another random orthogonal transformation. Note that participant consent and Data Use Limitations (DULs) differ within and across TOPMed studies. However, for variants present in multiple individuals we present arguments that suggest it would be very challenging to find the key and hence decrypt the data. Specifically, the score function is not locally convex, and any naive optimization attempt is bound to fall into local minima. 11 (Suppl. 26, 205213 (2005). Such a move, toward the idea that an alleles effects are public property while an individuals genotypes are private, is more important than the encryption mechanism used to attain it. In the example, SNP 1 has a smaller angle with the phenotype than SNP 2, and hence a stronger genetic association. A database of locus-specific databases. We note that the SNP identities (genomic positions) need to be distributed with the data to interpret the biology of any GWAS hits. Genotype versus phenotype. annotation of phenotypes associated with genotypes using terms from the Mammalian Phenotype Ontology and the association of mouse models with human disease. A potential concern is that rounding errors might arise due to the very large dimension of the key P. While case-control studies (, Are any nonorthogonal transformations suitable for HE? Our interpretation of this observation is that plaintext dosages correspond to a very special choice of coordinates where the standardized genotype dosages for a SNP are concentrated on three modes depending on the SNP allele frequency. We found that the estimates changed considerably and therefore orthogonal encryption is not homomorphic for logistic regression, for which we therefore recommend methods such as those of Wang et al. What is it? is supported by Biotechnology and Biological Sciences Research Council grants BB/S017372/1, BB/R01356X/1, BB/P024726/1, and BB/M011585/1. Second, genetic improvement of crops and farm animals could be accelerated. McKusick, V. A. Mendelian Inheritance in Man. Genotypes are encoded as imputed dosages clustered at the values 0,1,2 giving the numbers of alternate alleles. R.M. . The National Library of Medicine ( NLM) is pleased to announce that all controlled-access and publicly available data in SRA is now available through Google Cloud Platform (GCP) and Amazon Web Services (AWS). Likelihood-based inferences are unaffected by orthogonal encryption. Nat Rev Genet 10, 918 (2009). We submit this problem as an open challenge to the community, as described at https://github.com/encryption4genetics. Thus, it is possible to sample a random orthogonal matrix such that, on average, there is no correlation between a random input vector of genotypes and its orthogonal transformation. J. Hum. Quackenbush, J. Standardizing the standards. Keywords: Bioinformatics, Data Mining, Text classification, database of Genotypes and Phenotypes. 2), S88S122 (2003). Data . Next, we discuss strategies that might be used to decrypt the data, in likely increasing order of effectiveness. Nature Genet. HEGP cannot deal with missing data, which should be imputed first. BMC Bioinformatics 2, 7 (2001). The database of Genotypes and Phenotypes (dbGaP) is an NIH-maintained database of datasets developed to archive and distribute the results of studies that have investigated the interaction of genotype and phenotype. As FastICA attempts to maximize non-Gaussianity in the attempted decryption, these results imply that non-Gaussianity does not describe the plaintext sufficiently uniquely. The database of Genotypes and Phenotypes (dbGaP) contains various types of data generated from genome-wide association studies (GWAS). Fast Independent Components Analysis (FastICA) (Hyvrinen and Oja 1997) is another method that attempts to split non-Gaussian signals from Gaussian noise. Sign up for the Nature Briefing newsletter what matters in science, free to your inbox daily. Google Scholar. It also preserves linkage disequilibrium between genetic variants and associations between variants and phenotypes. However, after encryption and quantile normalization, the mean logP discrepancy rose slightly to 2.402102, maximum 2.257101, but the correlation was still > 0.99. The simulation of very large orthogonal keys (e.g., for hundreds of thousands of individuals) might also present technical difficulties. In Cho et al. Thus, should an effective attack be discovered, orthogonal keys still offer pretty good genetic privacy in the sense that they would prevent straightforward copying of information about individuals genotypes. It is obvious that any permutation of the rows of any key will transform the phenotype and genotypes in the same way, and so are functionally equivalent. 9, 678688 (2008). This will entail a distributed, decentralized network of interconnected information sources and analysis services, the first incarnations of which are now starting to appear. The additive genotype dosage matrix, The Pearson correlation between a standardized vector, Now the eigen decomposition of an orthogonal matrix can be written as, Suppose we wish to perform a federated mega-analysis on several genotype/phenotype sets. For the human depression data, we encrypted the phenotype and genotype dosages in 10 groups of 1000 individuals plus a final block of 664. Wang, X., Gorlitsky, R. & Almeida, J. S. From XML to RDF: how semantic web technologies will change the design of 'omic' standards. Therefore, dbGaP applicants will need to carefully review DULs and ensure that proposed Research Use Statements (RUS) are consistent with the study-consent group(s) being requested. We computed association across 160 k SNPs using both unencrypted and encrypted dosages. Overview The mixed-model transformation. We generated a random 10,46510,465 orthogonal matrix P10k, which took 1 hr with two cores and 8 GB of memory. 1b). Each party computes a normalized plaintext HR restricted to just these SNPs, and they share the dual ciphertext FR=HRPR, where PR is a random NRNR orthogonal key, instead of sharing F=PH. In a small minority of studies, anonymized data [that is, where the names of individuals have been replaced by anonymous identifiers (IDs)] are freely available for users to download and analyze. Bioinform. 28, 554562 (2007). Studying this set as varies lets us explore the encryption properties of a particular linear direction in the space of orthogonal matrices, starting at the identity matrix and passing through P [incidentally, the set P() forms a subgroup of the orthogonal matrices, such that P()P()=P(+), with inverse P()1=P(); this subgroup is of course isomorphic to the real numbers under addition]. (2017) Yaos protocol is used to identify rare Mendelian-type mutations shared between affected individuals. AWS and AWS Partners have tools and solutions to help you migrate and securely store genomic data in the AWS cloud, accelerate secondary and . FastICA, Fast Independent Components Analysis. Homer, N. et al. An ensemble learning approach for predicting phenotypes from genotypes Abstract: Genomic selection (GS) refers to a new breeding strategy that estimates breeding values through high-density markers covering the whole genome, and then sorts and selects them. Genet. Nature Biotechnol. If there is We found that these scores were much higher than the best keys generated during the brute-force attack. (2018), Tkachenko et al. A new project is created in dbGaP and access to granted to their eRA Commons ID. Examination of DNA variation (typically SNPs) across the whole genome in a large number of individuals who have been matched for population ancestry and assessed for a disease or trait of interest. Orthogonal encryption is certainly insecure for certain choices of P. The goal of the adversary is . (B) The same data after multiplication by an orthogonal matrix P (a rotation represented by the curved orange arrow). Suppose P is any orthogonal nn matrix, i.e., so that P1=PT. Nature Reviews Genetics Sim J. J., Chan F. M., Chen S., Tan B. H. M., Aung K. M. M., 2019Achieving GWAS with homomorphic encryption. a topic you are unsure about, please suggest it below. Cambon-Thomsen, A., Rial-Sebbag, E. & Knoppers, B. M. Trends in ethical and legal frameworks for the use of human biobanks. 1 Introduction. Stevens, R., Goble, C. A. TOPMed genomic data and pre-existing Parent study phenotypic data are made available to the scientific community in study-specific accessions in the database of Genotypes and Phenotypes (dbGaP) and in the NHLBI BioData Catalyst cloud platform. Saltz, J. et al. Nature Genet. Database of Genotypes and Phenotypes (dbGaP) Access dbGaP. Diergaarde, B. et al. volume10,pages 918 (2009)Cite this article. The cosines of the angles between the phenotype vector y and various SNPs equal the corresponding Pearson correlations, which are closely related to the t-statistics for testing association. The per-entry error in the decrypted data was 0.079 on average, which is quite good, while anything > 0.4 is unusable. Dowell, R. D. et al. It preserves linkage disequilibrium between genetic variants, and key association statistics including heritability between variants and phenotypes, while obscuring relationships between individuals. Miyazaki, S. et al. Twigger, S. N. et al. Berners-Lee, T., Hendler, J. Their major drawbacks are that they are unsuitable for logistic regression and that the method is not provably secure. 30, 373382 (2007). This suggests that quantile normalizing the ciphertext might improve security. Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database. Correspondence to We have a vector of phenotypes, y, and a matrix of genotypes, G. HEGP, homomorphic encryption for genotypes and phenotypes; QQ, quantilequantile. The GDC stores and distributes data that is considered "controlled access", meaning it contains some genotype information. Kauffmann, F. & Cambon-Thomsen, A. Tracing biological collections: between books and clinical trials. Along with emerging technologies that enhance connectivity and data retrieval, these advances should help to create a powerful knowledge environment for genotypephenotype information. Running mega analyses across TOPMed studies requires combining genotype and phenotype data across individual dbGaP accessions. More usuallyas for the UK BioBank and the UK 10k project, and studies deposited in the National Center for Biotechnology Information Database of Genotypes and Phenotypes and the European Bioinformatics Institute European Genome-phenome Archive (EGA)anonymized data are distributed only to researchers approved for access, whose institutions demonstrate that their computer systems are secure, and where they agree not to redistribute the data. This database is a look-up table in which the columns correspond to the genotypes of the SNPs of all the individuals (Fig. (D) The distribution of the same dosages after orthogonal transformation by multiplication by the orthogonal matrix P (black histogram) with the normal distribution with same mean and variance superimposed in red. Nucleic Acids Res. Summary: Based on the Genomic Data Sharing Policy issued in August 2007, the National Institutes of Health (NIH) has supported several repositories such as the database of Genotypes and Phenotypes (dbGaP). Assembling large collections of biosamples and associated information, for the purpose of biomedical investigation. Herein, we constructed a database of clinical phenotypes, genotypes and structures of mutant GLAs. First, the mean absolute discrepancy for mixed-model association logP values for the plaintext vs. HEGP ciphertext was 0.003141 (maximum 0.0263), and the overall correlation of logP values was 0.999: a close agreement. One potential difficulty when sharing encrypted data is the possibility of duplicates or close relatives occurring in different cohorts. (2018) and Sim et al. Thus HEGP alone induces only negligible reductions in the accuracy of association statistics and genotypes. Similarly, linkage disequilibrium R2 between any pair of SNPs is the square of the cosine of the angle between the SNPs. Date Published: 2020 Feb 15 Abstract: SUMMARY: Based on the Genomic Data Sharing Policy issued in August 2007, the National Institutes of Health (NIH) has supported several repositories such as the database of Genotypes and Phenotypes (dbGaP). Each key contains n(n+1)/2 independent double precision numbers, each of which can take 1020 possible values. Another way of thinking about the effects of the group of orthogonal transformations is that they define sets of equivalence classes of data sets D. 39, 1723 (2007). & Nabel, E. G. Protecting aggregate genomic data. 2016). Jones, A. R. et al. & Lassila, O. Towards practical privacy-preserving genome-wide association study. Bertsimas, D, O Nohadani, and K M Teo. Get the most important science stories of the day, free in your inbox. The conflicting demands of individual privacy vs. medical research have led to a spectrum of ways of sharing human genotype and phenotype data (Azencott 2018). The information that describes how genotypes connect to phenotypes, that is, the '2' in G2P, is even more complex. The genotype dosages are now represented by a continuum of real numbers. Merali, Z. However, if a covariate specifying sex is also encrypted then it would be possible to take sex into account when fitting the model. 23, 10991103 (2005). While it is simple to remove low-frequency variants and therefore protect against this weakness, the larger question of security remains. Nature Biotechnol. Wheeler, D. L. et al. 41, 687693 (2008). Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. PubMed and JavaScript. Nature Genet. When =0, then the correlations are all unity, as would be expected, but as increases we observe a damped oscillatory behavior, with mean correlation of 0 at approximately =1,2,3,. We assume that each set has first been imputed onto a common set of SNPs that are ordered consistently across data sets. We show that this is likely to be more secure than orthogonal transformation but is more limited in its applications. Law 26, 677697 (2007). Zerhouni, E. A. The same process is true for data submission when it contains genotype data. P.P. Databases in peril. However, we found that applying the implementation in the fastICA R package does not improve on our random brute-force attacks. Sci. The nm dosage matrix H has singular value decomposition H=UVT, where U is the nn orthogonal matrix of principal components, is nn diagonal, and VT is nm orthogonal. Horaitis, O. et al. Sparse whole-genome sequencing identifies two loci for major depressive disorder. 39, 425 (2007). The National Center for Biotechnology Information has created the dbGaP public repository for individual-level phenotype, exposure, genotype and sequence data and the associations between them. The flow of research data concerning the genetic basis of health and disease is rapidly increasing in speed and complexity. Researchers are able to access and download data from as well as contribute/submit data to the dbGaP. One solution would be to divide the samples into randomly chosen blocks of 10,000 individuals, sample a different transformation matrix to encrypt each block, and then permute all transformed data so that the block structure is hidden. 4, 337345 (2003). Attacks that exploit nonnormality in the encrypted data would be frustrated, potentially increasing security. HEGP has many desirable properties for quantitative genetics. We evaluated the effects of quantile normalization on the ciphertext mouse genotypes and platelet phenotypes. However, at this point, we know of no algorithm that can exploit this. It might be thought that orthogonal encryption is of little use, because both genotypes and phenotypes are transformed with the same orthogonal matrix, which must be known to those performing the transformation. Methods Clinical and neuropathological records of the National Alzheimer's Coordinating Center (NACC . So in defining evolution, we are really concerned with changes in the genotypes that make up a population from . & Giles, J. Nucleic Acids Res. The alternative of a partially centralized and partially federated model has been proposed to solve this problem. In summary, we have shown how to make a distinction between public information about genetic architecture and allelic effects, and private information about individuals. This is a recent comprehensive review of current and emerging components of informatics infrastructure for modern biological research. An organism's phenotype is all of its observable characteristics which are influenced both by its genotype and by the environment. The authors state that all data necessary for confirming the conclusions presented in the manuscript are represented fully within the manuscript. The authors acknowledge the valuable ideas, advice and funding provided by the GEN2PHEN project as part of the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement number 200754, which enabled the preparation of this Review. Smith, B. et al. (C) The distribution of dosages for a particular SNP (column of G), clustered around 0,1,2. Genetic information: special or not? Goble, C. & Stevens, R. State of the nation in data integration for bioinformatics. The black line shows the mean correlation P()(x) and the red lines the mean SD, estimated from 1000 individuals sampled from the CONVERGE study of major depressive disorder, at 1000 randomly chosen SNP sites. Another form of mathematical optimization is constrained convex programming, where constraints could be imposed to ensure the decrypted genotypes take plausible values. Interestingly, even for an 88 matrix, we could not identify a key that regenerated the plaintext and even good keys did not reflect the underlying genotypes fully. Genet. 2010), that recovers the correct genotypes accurately, or alternatively to show there are too many incorrect genotype-like decoy solutions far from the true answer, and that therefore the problem is essentially noninvertible. Stein, L. D. Towards a cyberinfrastructure for the biological sciences: progress, visions and challenges. The phenotype and each genotype vector (column of G) are standardized to have mean 0 and variance 1. Thus, if n=100, 1099 keys have to be tried before a good one is found. This database can be accessed as 'fabry-database.org', and is user friendly, being equipped with powerful computational tools. 2, 2006.0010 (2006). Phenotypes and genotypes are represented as unit vectors in a high-dimensional space. 2017), and on the smaller mouse data set of 1329 individuals and 19,877 SNPs from (Nicod et al. Open Access We defined a good key as one that gives a mean distance of < 0.4 between the genotype matrix and the attempted decryption. Each black dot represents one vector of genotypes. (A) A numeric phenotype vector y (left) and genotype dosage matrix G (right) are represented as colors and shades of gray. Corresponding author: Genetics Institute, University College London, Gower St., London WC1E 6BT, UK. The score is the L1 distance between matrices. At the other extreme, data sets are not distributed, but researchers may negotiate access to analyze the data on the hosts computer system (as in the UK 100,000 genomes project), or the host may agree to perform an analysis on behalf of an external user. GenBank. . & Brookes, A. Genotypephenotype databases: challenges and solutions for the post-genomic era. Similarly, a data set could also be subdivided into subsets (e.g., into male vs. female subjects) and each part encrypted separately so that subanalyses could be performed, and the subsets distributed separately. Content for each submitted study is comprehensive, including study documents (protocols, questionnaires, etc. Mailman, M. D. et al. Thorisson, G., Muilu, J. Volume 19, 2021, Pages 1603-1611 Database Article GPCards: An integrated database of genotype-phenotype correlations in human genetic diseases Bin Li a c e , Zheng Wang a , Qian Chen a , Kuokuo Li b , Xiaomeng Wang b , Yijing Wang b , Qian Zeng c , Ying Han b , Bin Lu d , Yuwen Zhao c , Rui Zhang c , Li Jiang c , Hongxu Pan c , Tengfei Luo b , COVID-19: Vaccine Program | Testing |Visitor Guidelines | Information for Employees. The average absolute difference between the logP values was 0.002. A blockchain-based framework to support pharmacogenetic data sharing, Neurocarta: aggregating and sharing disease-gene relations for the neurosciences, The Unique Evolutionary Signature of Genes Associated with Autism Spectrum Disorder, Managing sensitive phenotypic data and biomaterial in large-scale collaborative psychiatric genetic research projects: practical considerations, Computational tools for comparative phenomics: the role and promise of ontologies. Richard Mott and others, Private Genomes and Public SNPs: Homomorphic Encryption of Genotypes and Phenotypes for Shared Quantitative Genetics, Genetics, Volume 215, Issue 2, 1 June 2020, Pages 359372, https://doi.org/10.1534/genetics.120.303153. Correlation R2 of plaintext and ciphertext dosages as a function of minor allele frequency. However, note that factoring out those individuals with private variants does not reveal useful information about other unrelated individuals, because the remaining columns of P are in the subspace orthogonal to that spanned by the factored columns. The Mouse Genome Database: Genotypes, Phenotypes, and Models of Human Disease Carol J. Bult, Carol J. Bult * The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609 USA . 33, D514D517 (2005). Ioannidis, J. P. A. et al. Extrapolating from small matrices, we estimated a lower bound on the number of attempts required for solving an nn key of one good key generated per 10n1 incorrect keys. An organism's genotype is the set of genes that it carries. 1-877-NHLBI4U (1-877-645-2448)Learn more about getting to NIH, Policies:NHLBI Diversity, Equity and Inclusion Statement|Privacy Policy|Freedom of Information Act (FOIA)|Accessibility|Copyright and Usage|HHS Vulnerability Disclosure|No FEAR Act|Grants and Funding, Customer Service/Center for Health Information|Email Alerts|Jobs and Careers|Site Index, About NHLBI|National Institutes of Health|Department of Health and Human Services|OIG|USA.gov, Broad Institute and Beth Israel Proteomics Platform, View All TOPMed Projects and their Parent Studies, NIH-sponsored investigator-initiated award centered on TOPMed data, U01 Integrative Omics Approaches for Analysis of TOPMed Data, R01 Integrative Computational Biology for Analysis of NHLBI TOPMed Data, Parent Study Descriptions & Ethics Statements, DCC-harmonized phenotypes for the scientific community, Recommendations on the use and reporting of race, ethnicity, and ancestry in TOPMed, study-specific accessions in the database of Genotypes and Phenotypes (dbGaP), Instructions for controlled access to TOPMed sequence data on the cloud, Further documentation on dbGaP cloud access, including fusera, dbGaP instructions for requesting controlled-access data, BRAVO (BRowse All Variants Online) variant browser, dbSNP (Database of Single Nucleotide Polymorphisms, TOPMed Ancillary Session at 2020 ASHG annual meeting, TOPMed overview poster from the 2018 ASHG annual meeting, TOPMed design paper: Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program, NHLBI Diversity, Equity and Inclusion Statement, Customer Service/Center for Health Information. Database of the clinical phenotypes, genotypes and mutant arylsulfatase B structures in mucopolysaccharidosis type VI
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