Routes for breaching and protecting genetic privacy

We are entering the era of ubiquitous genetic information for research, clinical care, and personal curiosity. Sharing these datasets is vital for rapid progress in understanding the genetic basis of human diseases. However, one growing concern is the ability to protect the genetic privacy of the data originators. Here, we technically map threats to genetic privacy and discuss potential mitigation strategies for privacy-preserving dissemination of genetic data.Comment: Draft for comment

Cloud-Assisted Read Alignment and Privacy

Thanks to the rapid advances in sequencing technologies, genomic data is now being produced at an unprecedented rate. To adapt to this growth, several algorithms and paradigm shifts have been proposed to increase the throughput of the classical DNA workflow, e.g. by relying on the cloud to perform CPU intensive operations. However, the scientific community raised an alarm due to the possible privacy-related attacks that can be executed on genomic data. In this paper we review the state of the art in cloud-based alignment algorithms that have been developed for performance. We then present several privacy-preserving mechanisms that have been, or could be, used to align reads at an incremental performance cost. We finally argue for the use of risk analysis throughout the DNA workflow, to strike a balance between performance and protection of data

How can photo sharing inspire sharing genomes?

People usually are aware of the privacy risks of publish-ing photos online, but these risks are less evident when sharing humangenomes. Modern photos and sequenced genomes are both digital rep-resentations of real lives. They contain private information that maycompromise people’s privacy, and still, their highest value is most oftimes achieved only when sharing them with others. In this work, wepresent an analogy between the privacy aspects of sharing photos andsharing genomes, which clarifies the privacy risks in the latter to thegeneral public. Additionally, we illustrate an alternative informed modelto share genomic data according to the privacy-sensitivity level of eachportion. This article is a call to arms for a collaborative work between ge-neticists and security experts to build more effective methods to system-atically protect privacy, whilst promoting the accessibility and sharingof genome

Interpreting short tandem repeat variations in humans using mutational constraint

Identifying regions of the genome that are depleted of mutations can reveal potentially deleterious variants. Short tandem repeats (STRs), also known as microsatellites, are among the largest contributors of de novo mutations in humans. However, per-locus studies of STR mutations have been limited to highly ascertained panels of several dozen loci. Here, we harnessed bioinformatics tools and a novel analytical framework to estimate mutation parameters for each STR in the human genome by correlating STR genotypes with local sequence heterozygosity. We applied our method to obtain robust estimates of the impact of local sequence features on mutation parameters and used this to create a framework for measuring constraint at STRs by comparing observed vs. expected mutation rates. Constraint scores identified known pathogenic variants with early onset effects. Our metric will provide a valuable tool for prioritizing pathogenic STRs in medical genetics studies

Systematic multi-omics cell line profiling uncovers principles of Ewing sarcoma fusion oncogene-mediated gene regulation

Ewing sarcoma (EwS) is characterized by EWSR1-ETS fusion transcription factors converting polymorphic GGAA microsatellites (mSats) into potent neo-enhancers. Although the paucity of additional mutations makes EwS a genuine model to study principles of cooperation between dominant fusion oncogenes and neo-enhancers, this is impeded by the limited number of well-characterized models. Here we present the Ewing Sarcoma Cell Line Atlas (ESCLA), comprising whole-genome, DNA methylation, transcriptome, proteome, and chromatin immunoprecipitation sequencing (ChIP-seq) data of 18 cell lines with inducible EWSR1-ETS knockdown. The ESCLA shows hundreds of EWSR1-ETS-targets, the nature of EWSR1-ETS-preferred GGAA mSats, and putative indirect modes of EWSR1-ETS-mediated gene regulation, converging in the duality of a specific but plastic EwS signature. We identify heterogeneously regulated EWSR1-ETS-targets as potential prognostic EwS biomarkers. Our freely available ESCLA (http://r2platform.com/escla/) is a rich resource for EwS research and highlights the power of comprehensive datasets to unravel principles of heterogeneous gene regulation by chimeric transcription factors