Read mapping is a fundamental step in many genomics applications. It is used to identify potential matches and differences between fragments (called reads) of a sequenced genome and an already known genome (called a reference genome). Read mapping is costly because it needs to perform approximate string matching (ASM) on large amounts of data. To address the computational challenges in genome analysis, many prior works propose various approaches such as accurate filters that select the reads within a dataset of genomic reads (called a read set) that must undergo expensive computation, efficient heuristics, and hardware acceleration. While effective at reducing the amount of expensive computation, all such approaches still require the costly movement of a large amount of data from storage to the rest of the system, which can significantly lower the end-to-end performance of read mapping in conventional and emerging genomics systems.

A critical step of genome sequence analysis is the mapping of sequenced DNA fragments (i.e., reads) collected from an individual to a known linear reference genome sequence (i.e., sequence-to-sequence mapping). Recent works replace the linear reference sequence with a graph-based representation of the reference genome, which captures the genetic variations and diversity across many individuals in a population. Mapping reads to the graph-based reference genome (i.e., sequence-to-graph mapping) results in notable quality improvements in genome analysis. Unfortunately, while sequence-to-sequence mapping is well studied with many available tools and accelerators, sequence-to-graph mapping is a more difficult computational problem, with a much smaller number of practical software tools currently available.

Nanopore sequencing is a widely-used high-throughput genome sequencing technology that can sequence long fragments of a genome into raw electrical signals at low cost. Nanopore sequencing requires two computationally-costly processing steps for accurate downstream genome analysis. The first step, basecalling, translates the raw electrical signals into nucleotide bases (i.e., A, C, G, T). The second step, read mapping, finds the correct location of a read in a reference genome. In existing genome analysis pipelines, basecalling and read mapping are executed separately. We observe in this work that such separate execution of the two most time-consuming steps inherently leads to ❨1❩ significant data movement and ❨2❩ redundant computations on the data, slowing down the genome analysis pipeline. This paper proposes GenPIP, an in-memory genome analysis accelerator that tightly integrates basecalling and read mapping. GenPIP improves the petformance of the genome analysis pipeline with two key mechanisms: ❨1❩ in-memory fine-grained collaborative execution of the major genome analysis steps in parallel}; ❨2❩ a new technique for early-rejection of low-quality and unmapped reads to timely stop the execution of genome analysis for such reads, reducing inefficient computation. Our experiments show that, for the execution of the genome analysis pipeline, GenPIP provides 41.6$\times$ (8.4$\times$) speedup and 32.8$\times$ (20.8$\times$) energy savings with negligible accuracy loss compared to the state-of-the-art software genome analysis tools executed on a state-of-the-art CPU (GPU). Compared to a design that combines state-of-the-art in-memory basecalling and read mapping accelerators, GenPIP provides 1.39$\times$ speedup and 1.37$\times$ energy savings.

MOTIVATION: The rapid progress in genome sequencing has led to high availability of genomic data. Studying these data can greatly help answer the key questions about disease associations and our evolution. However, due to growing privacy concerns about the sensitive information of participants, accessing key results and data of genomic studies (such as genome-wide association studies) is restricted to only trusted individuals. On the other hand, paving the way to biomedical breakthroughs and discoveries requires granting open access to genomic datasets. Privacy-preserving mechanisms can be a solution for granting wider access to such data while protecting their owners. In particular, there has been growing interest in applying the concept of differential privacy (DP) while sharing summary statistics about genomic data. DP provides a mathematically rigorous approach to prevent the risk of membership inference while sharing statistical information about a dataset. However, DP does not consider the dependence between tuples in the dataset, which may degrade the privacy guarantees offered by the DP. RESULTS: In this work, focusing on genomic datasets, we show this drawback of the DP and we propose techniques to mitigate it. First, using a real-world genomic dataset, we demonstrate the feasibility of an inference attack on differentially private query results by utilizing the correlations between the entries in the dataset. The results show the scale of vulnerability when we have dependent tuples in the dataset. We show that the adversary can infer sensitive genomic data about a user from the differentially private results of a query by exploiting the correlations between the genomes of family members. Second, we propose a mechanism for privacy-preserving sharing of statistics from genomic datasets to attain privacy guarantees while taking into consideration the dependence between tuples. By evaluating our mechanism on different genomic datasets, we empirically demonstrate that our proposed mechanism can achieve up to 50% better privacy than traditional DP-based solutions. AVAILABILITY AND IMPLEMENTATION: https://github.com/nourmadhoun/Differential-privacy-genomic-inference-attack. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

MOTIVATION: The rapid decrease in the sequencing technology costs leads to a revolution in medical research and clinical care. Today, researchers have access to large genomic datasets to study associations between variants and complex traits. However, availability of such genomic datasets also results in new privacy concerns about personal information of the participants in genomic studies. Differential privacy (DP) is one of the rigorous privacy concepts, which received widespread interest for sharing summary statistics from genomic datasets while protecting the privacy of participants against inference attacks. However, DP has a known drawback as it does not consider the correlation between dataset tuples. Therefore, privacy guarantees of DP-based mechanisms may degrade if the dataset includes dependent tuples, which is a common situation for genomic datasets due to the inherent correlations between genomes of family members. RESULTS: In this article, using two real-life genomic datasets, we show that exploiting the correlation between the dataset participants results in significant information leak from differentially private results of complex queries. We formulate this as an attribute inference attack and show the privacy loss in minor allele frequency (MAF) and chi-square queries. Our results show that using the results of differentially private MAF queries and utilizing the dependency between tuples, an adversary can reveal up to 50% more sensitive information about the genome of a target (compared to original privacy guarantees of standard DP-based mechanisms), while differentially privacy chi-square queries can reveal up to 40% more sensitive information. Furthermore, we show that the adversary can use the inferred genomic data obtained from the attribute inference attack to infer the membership of a target in another genomic dataset (e.g. associated with a sensitive trait). Using a log-likelihood-ratio test, our results also show that the inference power of the adversary can be significantly high in such an attack even using inferred (and hence partially incorrect) genomes. AVAILABILITY AND IMPLEMENTATION: https://github.com/nourmadhoun/Inference-Attacks-Differential-Privacy.