Due to its hereditary nature, genomic data is not only linked to its owner but to that of close relatives as well. As a result, its sensitivity does not really degrade over time; in fact, the relevance of a genomic sequence is likely to be longer than the security provided by encryption. This prompts the need for specialized techniques providing long-term security for genomic data, yet the only available tool for this purpose is GenoGuard (, 2015). By relying on Honey Encryption, GenoGuard is secure against an adversary that can brute force all possible keys; i.e., whenever an attacker tries to decrypt using an incorrect password, she will obtain an incorrect but plausible looking decoy sequence. In this paper, we set to analyze the real-world security guarantees provided by GenoGuard; specifically, assess how much more information does access to a ciphertext encrypted using GenoGuard yield, compared to one that was not. Overall, we find that, if the adversary has access to side information in the form of partial information from the target sequence, the use of GenoGuard does appreciably increase her power in determining the rest of the sequence. We show that, in the case of a sequence encrypted using an easily guessable (low-entropy) password, the adversary is able to rule out most decoy sequences, and obtain the target sequence with just 2.5 of it available as side information. In the case of a harder-to-guess (high-entropy) password, we show that the adversary still obtains, on average, better accuracy in guessing the rest of the target sequences than using state-of-the-art genomic sequence inference methods, obtaining up to 15 improvement in accuracy.
Membership inference. @cite_33 present a membership inference attack in which they infer the presence of an individual's genotype within a complex genomic DNA mixture. @cite_2 improve on the attack using correlation statistics of just a few hundreds SNPs, while @cite_16 rely on regression coefficients. Shringarpure and Bustamante @cite_30 perform membership inference against the Beacon network. Beacons are web servers that answer questions e.g. does your dataset include a genome that has a specific nucleotide at a specific genomic coordinate?'' to which the Beacon responds yes or no, without referring to a specific individual; see: https: github.com ga4gh-beacon specification . They use a likelihood-ratio test to predict whether an individual is present in the Beacon, detecting membership within a Beacon with 1,000 individuals using 5,000 queries. Also, Von @cite_9 reduce the number of queries to less than 0.5 best performing attack uses a high-order Markov chain to model the SNP correlations, as described in @cite_11 . Note that, as part of the attacks described in this paper, we use inference methods from @cite_11 as our baseline inference methods.
@cite_30 @cite_33 @cite_9 @cite_2 @cite_16 @cite_11
2952306472 1838635991 2532520288 2040228409
Genomic datasets are often associated with sensitive phenotypes. Therefore, the leak of membership information is a major privacy risk. Genomic beacons aim to provide a secure, easy to implement, and standardized interface for data sharing by only allowing yes no queries on the presence of specific alleles in the dataset. Previously deemed secure against re-identification attacks, beacons were shown to be vulnerable despite their stringent policy. Recent studies have demonstrated that it is possible to determine whether the victim is in the dataset, by repeatedly querying the beacon for his her single nucleotide polymorphisms (SNPs). In this work, we propose a novel re-identification attack and show that the privacy risk is more serious than previously thought. Using the proposed attack, even if the victim systematically hides informative SNPs (i.e., SNPs with very low minor allele frequency -MAF-), it is possible to infer the alleles at positions of interest as well as the beacon query results with very high confidence. Our method is based on the fact that alleles at different loci are not necessarily independent. We use the linkage disequilibrium and a high-order Markov chain-based algorithm for the inference. We show that in a simulated beacon with 65 individuals from the CEU population, we can infer membership of individuals with 95 confidence with only 5 queries, even when SNPs with MAF less than 0.05 are hidden. This means, we need less than 0.5 of the number of queries that existing works require, to determine beacon membership under the same conditions. We further show that countermeasures such as hiding certain parts of the genome or setting a query budget for the user would fail to protect the privacy of the participants under our adversary model. The human genetics community needs robust protocols that enable secure sharing of genomic data from participants in genetic research. Beacons are web servers that answer allele-presence queries—such as “Do you have a genome that has a specific nucleotide (e.g., A) at a specific genomic position (e.g., position 11,272 on chromosome 1)?”—with either “yes” or “no.” Here, we show that individuals in a beacon are susceptible to re-identification even if the only data shared include presence or absence information about alleles in a beacon. Specifically, we propose a likelihood-ratio test of whether a given individual is present in a given genetic beacon. Our test is not dependent on allele frequencies and is the most powerful test for a specified false-positive rate. Through simulations, we showed that in a beacon with 1,000 individuals, re-identification is possible with just 5,000 queries. Relatives can also be identified in the beacon. Re-identification is possible even in the presence of sequencing errors and variant-calling differences. In a beacon constructed with 65 European individuals from the 1000 Genomes Project, we demonstrated that it is possible to detect membership in the beacon with just 250 SNPs. With just 1,000 SNP queries, we were able to detect the presence of an individual genome from the Personal Genome Project in an existing beacon. Our results show that beacons can disclose membership and implied phenotypic information about participants and do not protect privacy a priori. We discuss risk mitigation through policies and standards such as not allowing anonymous pings of genetic beacons and requiring minimum beacon sizes. The continuous decrease in cost of molecular profiling tests is revolutionizing medical research and practice, but it also raises new privacy concerns. One of the first attacks against privacy of biological data, proposed by in 2008, showed that, by knowing parts of the genome of a given individual and summary statistics of a genome-based study, it is possible to detect if this individual participated in the study. Since then, a lot of work has been carried out to further study the theoretical limits and to counter the genome-based membership inference attack. However, genomic data are by no means the only or the most influential biological data threatening personal privacy. For instance, whereas the genome informs us about the risk of developing some diseases in the future, epigenetic biomarkers, such as microRNAs, are directly and deterministically affected by our health condition including most common severe diseases. In this paper, we show that the membership inference attack also threatens the privacy of individuals contributing their microRNA expressions to scientific studies. Our results on real and public microRNA expression data demonstrate that disease-specific datasets are especially prone to membership detection, offering a true-positive rate of up to 77 at a false-negative rate of less than 1 . We present two attacks: one relying on the L_1 distance and the other based on the likelihood-ratio test. We show that the likelihood-ratio test provides the highest adversarial success and we derive a theoretical limit on this success. In order to mitigate the membership inference, we propose and evaluate both a differentially private mechanism and a hiding mechanism. We also consider two types of adversarial prior knowledge for the differentially private mechanism and show that, for relatively large datasets, this mechanism can protect the privacy of participants in miRNA-based studies against strong adversaries without degrading the data utility too much. Based on our findings and given the current number of miRNAs, we recommend to only release summary statistics of datasets containing at least a couple of hundred individuals. We use high-density single nucleotide polymorphism (SNP) genotyping microarrays to demonstrate the ability to accurately and robustly determine whether individuals are in a complex genomic DNA mixture. We first develop a theoretical framework for detecting an individual's presence within a mixture, then show, through simulations, the limits associated with our method, and finally demonstrate experimentally the identification of the presence of genomic DNA of specific individuals within a series of highly complex genomic mixtures, including mixtures where an individual contributes less than 0.1 of the total genomic DNA. These findings shift the perceived utility of SNPs for identifying individual trace contributors within a forensics mixture, and suggest future research efforts into assessing the viability of previously sub-optimal DNA sources due to sample contamination. These findings also suggest that composite statistics across cohorts, such as allele frequency or genotype counts, do not mask identity within genome-wide association studies. The implications of these findings are discussed.