The Signal Private Group System and Anonymous Credentials Supporting Efficient Verifiable Encryption

In this paper we present a system for maintaining a membership list of users in a group, designed for use in the Signal Messenger secure messaging app. The goal is to support $\mathit{private}$ $\mathit{groups}$ where membership information is readily available to all group members but hidden from the service provider or anyone outside the group. In the proposed solution, a central server stores the group membership in the form of encrypted entries. Members of the group authenticate to the server in a way that reveals only that they correspond to some encrypted entry, then read and write the encrypted entries. Authentication in our design uses a primitive called a keyed-verification anonymous credential (KVAC), and we construct a new KVAC scheme based on an algebraic MAC, instantiated in a group $\mathbb{G}$ of prime order. The benefit of the new KVAC is that attributes may be elements in $\mathbb{G}$, whereas previous schemes could only support attributes that were integers modulo the order of $\mathbb{G}$. This enables us to encrypt group data using an efficient Elgamal-like encryption scheme, and to prove in zero-knowledge that the encrypted data is certified by a credential. Because encryption, authentication, and the associated proofs of knowledge are all instantiated in $\mathbb{G}$ the system is efficient, even for large groups

Proofs of discrete logarithm equality across groups

We provide a $\Sigma$-protocol for proving that two values committed in different groups are equal. We study our protocol in Lyubashevsky\u27s framework Fiat-Shamir with aborts (Asiacrypt’09) and offer concrete parameters for instantiating it. We explain how to use it to compose SNARKs with $\Sigma$-protocols, create efficient proofs of solvency on cryptocurrencies, and join of attributes across different anonymous credentials

Discovery and characterization of artifactual mutations in deep coverage targeted capture sequencing data due to oxidative DNA damage during sample preparation

As researchers begin probing deep coverage sequencing data for increasingly rare mutations and subclonal events, the fidelity of next generation sequencing (NGS) laboratory methods will become increasingly critical. Although error rates for sequencing and polymerase chain reaction (PCR) are well documented, the effects that DNA extraction and other library preparation steps could have on downstream sequence integrity have not been thoroughly evaluated. Here, we describe the discovery of novel C > A/G > T transversion artifacts found at low allelic fractions in targeted capture data. Characteristics such as sequencer read orientation and presence in both tumor and normal samples strongly indicated a non-biological mechanism. We identified the source as oxidation of DNA during acoustic shearing in samples containing reactive contaminants from the extraction process. We show generation of 8-oxoguanine (8-oxoG) lesions during DNA shearing, present analysis tools to detect oxidation in sequencing data and suggest methods to reduce DNA oxidation through the introduction of antioxidants. Further, informatics methods are presented to confidently filter these artifacts from sequencing data sets. Though only seen in a low percentage of reads in affected samples, such artifacts could have profoundly deleterious effects on the ability to confidently call rare mutations, and eliminating other possible sources of artifacts should become a priority for the research community.National Human Genome Research Institute (U.S.) (HG03067-05

Structural insights into the transcriptional and translational roles of Ebp1.

Accepted versio

Widening of the genetic and clinical spectrum of Lamb-Shaffer syndrome, a neurodevelopmental disorder due to SOX5 haploinsufficiency

Purpose Lamb-Shaffer syndrome (LAMSHF) is a neurodevelopmental disorder described in just over two dozen patients with heterozygous genetic alterations involving SOX5, a gene encoding a transcription factor regulating cell fate and differentiation in neurogenesis and other discrete developmental processes. The genetic alterations described so far are mainly microdeletions. The present study was aimed at increasing our understanding of LAMSHF, its clinical and genetic spectrum, and the pathophysiological mechanisms involved. Methods Clinical and genetic data were collected through GeneMatcher and clinical or genetic networks for 41 novel patients harboring various types ofSOX5 alterations. Functional consequences of selected substitutions were investigated. Results Microdeletions and truncating variants occurred throughout SOX5. In contrast, most missense variants clustered in the pivotal SOX-specific high-mobility-group domain. The latter variants prevented SOX5 from binding DNA and promoting transactivation in vitro, whereas missense variants located outside the high-mobility-group domain did not. Clinical manifestations and severity varied among patients. No clear genotype-phenotype correlations were found, except that missense variants outside the high-mobility-group domain were generally better tolerated. Conclusions This study extends the clinical and genetic spectrum associated with LAMSHF and consolidates evidence that SOX5 haploinsufficiency leads to variable degrees of intellectual disability, language delay, and other clinical features

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead