The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

Integrative analysis of 111 reference human epigenomes

Today’s artificial intelligence still faces two major challenges. One is that, in most industries, data exists in the form of isolated islands. The other is the strengthening of data privacy and security. We propose a possible solution to these challenges: secure federated learning. Beyond the federated-learning framework first proposed by Google in 2016, we introduce a comprehensive secure federated-learning framework, which includes horizontal federated learning, vertical federated learning, and federated transfer learning. We provide definitions, architectures, and applications for the federated-learning framework, and provide a comprehensive survey of existing works on this subject. In addition, we propose building data networks among organizations based on federated mechanisms as an effective solution to allowing knowledge to be shared without compromising user privacy.

Federated Machine Learning: Concept and Applications

Usually, a proof of a theorem contains more knowledge than the mere fact that the theorem is true. For instance, to prove that a graph is Hamiltonian it suffices to exhibit a Hamiltonian tour in it; however, this seems to contain more knowledge than the single bit Hamiltonian/non-Hamiltonian.In this paper a computational complexity theory of the “knowledge” contained in a proof is developed. Zero-knowledge proofs are defined as those proofs that convey no additional knowledge other than the correctness of the proposition in question. Examples of zero-knowledge proof systems are given for the languages of quadratic residuosity and 'quadratic nonresiduosity. These are the first examples of zero-knowledge proofs for languages not known to be efficiently recognizable.

/pdf/the-knowledge-complexity-of-interactive-proof-systems-31apre0ecf.pdf

The knowledge complexity of interactive proof-systems

Medical genetics was revolutionized during the 1980s by the application of genetic mapping to locate the genes responsible for simple Mendelian diseases. Most diseases and traits, however, do not follow simple inheritance patterns. Geneticists have thus begun taking up the even greater challenge of the genetic dissection of complex traits. Four major approaches have been developed: linkage analysis, allele-sharing methods, association studies, and polygenic analysis of experimental crosses. This article synthesizes the current state of the genetic dissection of complex traits—describing the methods, limitations, and recent applications to biological problems.

Genetic Dissection of Complex Traits

Emerging smart contract systems over decentralized cryptocurrencies allow mutually distrustful parties to transact safely without trusted third parties. In the event of contractual breaches or aborts, the decentralized blockchain ensures that honest parties obtain commensurate compensation. Existing systems, however, lack transactional privacy. All transactions, including flow of money between pseudonyms and amount transacted, are exposed on the blockchain. We present Hawk, a decentralized smart contract system that does not store financial transactions in the clear on the blockchain, thus retaining transactional privacy from the public's view. A Hawk programmer can write a private smart contract in an intuitive manner without having to implement cryptography, and our compiler automatically generates an efficient cryptographic protocol where contractual parties interact with the blockchain, using cryptographic primitives such as zero-knowledge proofs. To formally define and reason about the security of our protocols, we are the first to formalize the blockchain model of cryptography. The formal modeling is of independent interest. We advocate the community to adopt such a formal model when designing applications atop decentralized blockchains.

https://www.the-blockchain.com/docs/Hawk%20-%20The%20Blockchain%20Model%20of%20Cryptography%20and%20Privacy-Preserving%20Smart%20Contracts.pdf

Hawk: The Blockchain Model of Cryptography and Privacy-Preserving Smart Contracts

Motivation: The continued progress in developing technological platforms, availability of many published experimental datasets, as well as different statistical methods to analyze those data have allowed approaching the same research question using various methods simultaneously. To get the best out of all these alternatives, we need to integrate their results in an unbiased manner. Prioritized gene lists are a common result presentation method in genomic data analysis applications. Thus, the rank aggregation methods can become a useful and general solution for the integration task.

Results: Standard rank aggregation methods are often ill-suited for biological settings where the gene lists are inherently noisy. As a remedy, we propose a novel robust rank aggregation (RRA) method. Our method detects genes that are ranked consistently better than expected under null hypothesis of uncorrelated inputs and assigns a significance score for each gene. The underlying probabilistic model makes the algorithm parameter free and robust to outliers, noise and errors. Significance scores also provide a rigorous way to keep only the statistically relevant genes in the final list. These properties make our approach robust and compelling for many settings.

Availability: All the methods are implemented as a GNU R package RobustRankAggreg, freely available at the Comprehensive R Archive Network http://cran.r-project.org/.

Contact: [email protected]

Supplementary informationSupplementary data are available at Bioinformatics online.

/pdf/robust-rank-aggregation-for-gene-list-integration-and-meta-4ij6yw6c1s.pdf

Robust rank aggregation for gene list integration and meta-analysis

Gathering and processing sensitive data is a difficult task. In fact, there is no common recipe for building the necessary information systems. In this paper, we present a provably secure and efficient general-purpose computation system to address this problem. Our solution-- Sharemind --is a virtual machine for privacy-preserving data processing that relies on share computing techniques. This is a standard way for securely evaluating functions in a multi-party computation environment. The novelty of our solution is in the choice of the secret sharing scheme and the design of the protocol suite. We have made many practical decisions to make large-scale share computing feasible in practice. The protocols of Sharemind are information-theoretically secure in the honest-but-curious model with three computing participants. Although the honest-but-curious model does not tolerate malicious participants, it still provides significantly increased privacy preservation when compared to standard centralised databases.

/pdf/sharemind-a-framework-for-fast-privacy-preserving-5a2ope8wo5.pdf

Sharemind: A Framework for Fast Privacy-Preserving Computations

In mining and integrating data from multiple sources, there are many privacy and security issues. In several different contexts, the security of the full privacy-preserving data mining protocol depends on the security of the underlying private scalar product protocol. We show that two of the private scalar product protocols, one of which was proposed in a leading data mining conference, are insecure. We then describe a provably private scalar product protocol that is based on homomorphic encryption and improve its efficiency so that it can also be used on massive datasets.

/pdf/on-private-scalar-product-computation-for-privacy-preserving-4hklhxww6a.pdf

On private scalar product computation for privacy-preserving data mining

Solutions for an easy and secure setup of a wireless connection between two devices are urgently needed for WLAN, Wireless USB, Bluetooth and similar standards for short range wireless communication. All such key exchange protocols employ data authentication as an unavoidable subtask. As a solution, we propose an asymptotically optimal protocol family for data authentication that uses short manually authenticated out-of-band messages. Compared to previous articles by Vaudenay and Pasini the results of this paper are more general and based on weaker security assumptions. In addition to providing security proofs for our protocols, we focus also on implementation details and propose practically secure and efficient sub-primitives for applications.

/pdf/efficient-mutual-data-authentication-using-manually-3magn28hrf.pdf

Efficient mutual data authentication using manually authenticated strings

Motivation: Increased availability of various genotyping techniques has initiated a race for finding genetic markers that can be used in diagnostics and personalized medicine. Although many genetic risk factors are known, key causes of common diseases with complex heritage patterns are still unknown. Identification of such complex traits requires a targeted study over a large collection of data. Ideally, such studies bring together data from many biobanks. However, data aggregation on such a large scale raises many privacy issues.

Results: We show how to conduct such studies without violating privacy of individual donors and without leaking the data to third parties. The presented solution has provable security guarantees.

Contact: [email protected]

Supplementary information: Supplementary data are available at Bioinformatics online.

/pdf/a-new-way-to-protect-privacy-in-large-scale-genome-wide-1g9uujr166.pdf

Sven Laur

Papers

Robust rank aggregation for gene list integration and meta-analysis

Sharemind: A Framework for Fast Privacy-Preserving Computations

On private scalar product computation for privacy-preserving data mining

Efficient mutual data authentication using manually authenticated strings

A new way to protect privacy in large-scale genome-wide association studies