Assessing and managing risk when sharing aggregate genetic variant data

Access to genetic data across studies is an important aspect of identifying new genetic associations through genome-wide association studies (GWASs). Meta-analysis across multiple GWASs with combined cohort sizes of tens of thousands of individuals often uncovers many more genome-wide associated loci than the original individual studies; this emphasizes the importance of tools and mechanisms for data sharing. However, even sharing summary-level data, such as allele frequencies, inherently carries some degree of privacy risk to study participants. Here we discuss mechanisms and resources for sharing data from GWASs, particularly focusing on approaches for assessing and quantifying the privacy risks to participants that result from the sharing of summary-level data.     

Public Opinion about the Importance of Privacy in Biobank Research

Concerns about privacy may deter people from participating in genetic research. Recruitment and retention of biobank participants requires understanding the nature and magnitude of these concerns. Potential participants in a proposed biobank were asked about their willingness to participate, their privacy concerns, informed consent, and data sharing. A representative survey of 4659 U.S. adults was conducted. Ninety percent of respondents would be concerned about privacy, 56% would be concerned about researchers having their information, and 37% would worry that study data could be used against them. However, 60% would participate in the biobank if asked. Nearly half (48%) would prefer to provide consent once for all research approved by an oversight panel, whereas 42% would prefer to provide consent for each project separately. Although 92% would allow academic researchers to use study data, 80% and 75%, respectively, would grant access to government and industry researchers. Concern about privacy was related to lower willingness to participate only when respondents were told that they would receive $50 for participation and would not receive individual research results back. Among respondents who were told that they would receive $200 or individual research results, privacy concerns were not related to willingness. Survey respondents valued both privacy and participation in biomedical research. Despite pervasive privacy concerns, 60% would participate in a biobank. Assuring research participants that their privacy will be protected to the best of researchers'' abilities may increase participants'' acceptance of consent for broad research uses of biobank data by a wide range of researchers.     

Privacy Risks from Genomic Data-Sharing Beacons

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.     

Mobilizing the base of neuroscience data: the case of neuronal morphologies

Despite the explosive growth of bioinformatics, data sharing has not yet become routine in neuroscience, possibly because of several broad-spanning issues, from data heterogeneity to privacy regulations. We present the case of neuronal morphology as an ideal example of shareable data. Drawing from recent experience, we argue that the tremendous research potential of existing (and largely unused) digital reconstructions should diffuse any reticence to sharing this type of data.     

Consent and confidentiality in the light of recent demands for data sharing

Many attempts have been made to formalize ethical requirements for research. Among the most prominent mechanisms are informed consent requirements and data protection regimes. These mechanisms, however, sometimes appear as obstacles to research. In this opinion paper, we critically discuss conventional approaches to research ethics that emphasize consent and data protection. Several recent debates have highlighted other important ethical issues and underlined the need for greater openness in order to uphold the integrity of health‐related research. Some of these measures, such as the sharing of individual‐level data, pose problems for standard understandings of consent and privacy. Here, we argue that these interpretations tend to be overdemanding: They do not really protect research subjects and they hinder the research process. Accordingly, we suggest another way of framing these requirements. Individual consent must be situated alongside the wider distribution of knowledge created when the actions, commitments, and procedures of researchers and their institutions are opened to scrutiny. And instead of simply emphasizing privacy or data protection, we should understand confidentiality as a principle that facilitates the sharing of information while upholding important safeguards. Consent and confidentiality belong to a broader set of safeguards and procedures to uphold the integrity of the research process.     

Inferential Genotyping of Y Chromosomes in Latter-Day Saints Founders and Comparison to Utah Samples in the HapMap Project

One concern in human genetics research is maintaining the privacy of study participants. The growth in genealogical registries may contribute to loss of privacy, given that genotypic information is accessible online to facilitate discovery of genetic relationships. Through iterative use of two such web archives, FamilySearch and Sorenson Molecular Genealogy Foundation, I was able to discern the likely haplotypes for the Y chromosomes of two men, Joseph Smith and Brigham Young, who were instrumental in the founding of the Latter-Day Saints Church. I then determined whether any of the Utahns who contributed to the HapMap project (the “CEU” set) is related to either man, on the basis of haplotype analysis of the Y chromosome. Although none of the CEU contributors appear to be a male-line relative, I discovered that predictions could be made for the surnames of the CEU participants by a similar process. For 20 of the 30 unrelated CEU samples, at least one exact match was revealed, and for 17 of these, a potential ancestor from Utah or a neighboring state could be identified. For the remaining ten samples, a match was nearly perfect, typically deviating by only one marker repeat unit. The same query performed in two other large databases revealed fewer individual matches and helped to clarify which surname predictions are more likely to be correct. Because large data sets of genotypes from both consenting research subjects and individuals pursuing genetic genealogy will be accessible online, this type of triangulation between databases may compromise the privacy of research subjects.     

The Disclosure of Genetic Information: A Human Research Ethics Perspective

Increasing emphasis on genetic research means that growing numbers of human research projects in Australia will involve complex issues related to genetic privacy, familial information and genetic epidemiology. The Office of Population Health Genomics (Department of Health, Western Australia) hosted an interactive workshop to explore the ethical issues involved in the disclosure of genetic information, where researchers and members of human research ethics committees (HRECs) were asked to consider several case studies from an ethical perspective. Workshop participants used a variety of approaches to examine the complex ethical issues encountered, but did not consistently refer to the values and principles outlined in the National Statement on Ethical Conduct in Human Research (NHMRC 2007) or apply rational ethical approaches. Overall, the data suggested that both researchers and HREC members may benefit from further education and support regarding the application of ethical frameworks to the issues encountered in genetic research.     

A Game Theoretic Framework for Analyzing Re-Identification Risk

Given the potential wealth of insights in personal data the big databases can provide, many organizations aim to share data while protecting privacy by sharing de-identified data, but are concerned because various demonstrations show such data can be re-identified. Yet these investigations focus on how attacks can be perpetrated, not the likelihood they will be realized. This paper introduces a game theoretic framework that enables a publisher to balance re-identification risk with the value of sharing data, leveraging a natural assumption that a recipient only attempts re-identification if its potential gains outweigh the costs. We apply the framework to a real case study, where the value of the data to the publisher is the actual grant funding dollar amounts from a national sponsor and the re-identification gain of the recipient is the fine paid to a regulator for violation of federal privacy rules. There are three notable findings: 1) it is possible to achieve zero risk, in that the recipient never gains from re-identification, while sharing almost as much data as the optimal solution that allows for a small amount of risk; 2) the zero-risk solution enables sharing much more data than a commonly invoked de-identification policy of the U.S. Health Insurance Portability and Accountability Act (HIPAA); and 3) a sensitivity analysis demonstrates these findings are robust to order-of-magnitude changes in player losses and gains. In combination, these findings provide support that such a framework can enable pragmatic policy decisions about de-identified data sharing.     

Realizing benefit sharing - the case of post-study obligations

In 2006, the Indonesian government decided to withhold avian flu samples from the World Health Organization. They argued that even though Indonesian samples were crucial to the development of vaccines, the results of vaccine research would be unaffordable for its citizens. Commentaries on the case varied from alleging blackmail to welcoming this strong stance against alleged exploitation. What is clear is that the concern expressed is related to benefit sharing. Benefit sharing requires resource users to return benefits to resource providers in order to achieve justice. One benefit sharing tool within health research is the duty to provide a health care intervention which has been proven to be beneficial (or alternative benefits) to research participants after a study has been concluded. This duty is generally known as a post-study obligation. It was enshrined in the Declaration of Helsinki in 2000 and re-emphasized in 2008. Yet, there are few, if any, examples of good practice. In this article, we analyse the obstacles to giving more bite to benefit sharing provisions in health research through ethical review. We conclude that the provision of post-study access to healthcare interventions is not a promising mechanism when monitored through research ethics committees. Alternative benefit provision is preferable if one focuses on achieving compliance. However, even the latter faces challenges, which we address in specific recommendations.     

ISBP: Understanding the Security Rule of Users' Information-Sharing Behaviors in Partnership

The rapid growth of social network data has given rise to high security awareness among users, especially when they exchange and share their personal information. However, because users have different feelings about sharing their information, they are often puzzled about who their partners for exchanging information can be and what information they can share. Is it possible to assist users in forming a partnership network in which they can exchange and share information with little worry? We propose a modified information sharing behavior prediction (ISBP) model that can help in understanding the underlying rules by which users share their information with partners in light of three common aspects: what types of items users are likely to share, what characteristics of users make them likely to share information, and what features of users’ sharing behavior are easy to predict. This model is applied with machine learning techniques in WEKA to predict users’ decisions pertaining to information sharing behavior and form them into trustable partnership networks by learning their features. In the experiment section, by using two real-life datasets consisting of citizens’ sharing behavior, we identify the effect of highly sensitive requests on sharing behavior adjacent to individual variables: the younger participants’ partners are more difficult to predict than those of the older participants, whereas the partners of people who are not computer majors are easier to predict than those of people who are computer majors. Based on these findings, we believe that it is necessary and feasible to offer users personalized suggestions on information sharing decisions, and this is pioneering work that could benefit college researchers focusing on user-centric strategies and website owners who want to collect more user information without raising their privacy awareness or losing their trustworthiness.     

Disclosure of genetic information obtained through research

The rapid expansion of information and knowledge of genetics has implications for the question of whether, and under what circumstances, information discovered in the course of genetic research should be conveyed to research participants and/or their relatives. The aim of this paper is to propose an ethically defensible solution to a specific case example illustrating this problem. To do this we reviewed the literature to find answers to the following three questions: (1) What do current regulations, guidelines, and commentary say about the disclosure of genetic risk information obtained through research to research participants? (2) What do current regulations, guidelines, and commentary say about the disclosure of genetic risk information obtained through research to the relatives of research subjects? and (3) What do current regulations, guidelines, and commentary say about the disclosure of genetic risk information obtained through research about former research participants who are now deceased? Our conclusion is that current U.S. federal guidelines governing the use of human subjects in research, as well as much of the current literature, do not adequately address the familial dimension inherent in genetic research, are virtually silent on the issue of sharing information of relevance to family members, and do not protect the deceased. It is our belief that this omission needs to be corrected and that explicit guidance on this issue needs to be provided to institutional review boards and researchers alike.     

HydroServer Lite as an open source solution for archiving and sharing environmental data for independent university labs

Managing, archiving, and sharing large amounts of data are essential tasks in ecological laboratories, and detailed data management plans are now required by major funding agencies. Many independent research labs may lack the technical or financial resources needed to support some of the more comprehensive data management solutions that have become available. In this paper we describe an open-source solution to data management, archiving, and sharing that can be implemented and customized by someone with limited computer programming experience using free software and standardized web services. This software, HydroServer Lite, is a light-weight database and data management web-based application that integrates with and makes data available on a large data sharing network developed by the Consortium of Universities for the Advancement of Hydrologic Sciences, Inc. (CUAHSI). The CUAHSI Hydrologic Information System facilitates data sharing through a network of local HydroServers that are registered with the central registry. Each HydroServer may contain a variety of ecological and climate data, stored in a standardized relational database model. Someone searching for data that are registered in the central registry can query the network by source, location, variable type, and dates. These data can be downloaded from the local HydroServer to a computer in an office or lab where they can be manipulated and analyzed without compromising the data in the archives. We offer this HydroServer Lite case study as a possible solution for independent research laboratories looking for a data management system that requires little technical expertise or initial cost to set up.     

Identifiability in biobanks: models,measures, and mitigation strategies

The collection and sharing of person-specific biospecimens has raised significant questions regarding privacy. In particular, the question of identifiability, or the degree to which materials stored in biobanks can be linked to the name of the individuals from which they were derived, is under scrutiny. The goal of this paper is to review the extent to which biospecimens and affiliated data can be designated as identifiable. To achieve this goal, we summarize recent research in identifiability assessment for DNA sequence data, as well as associated demographic and clinical data, shared via biobanks. We demonstrate the variability of the degree of risk, the factors that contribute to this variation, and potential ways to mitigate and manage such risk. Finally, we discuss the policy implications of these findings, particularly as they pertain to biobank security and access policies. We situate our review in the context of real data sharing scenarios and biorepositories.     

Research Stakeholders’ Views on Benefits and Challenges for Public Health Research Data Sharing in Kenya: The Importance of Trust and Social Relations

Background

There is increasing recognition of the importance of sharing research data within the international scientific community, but also of the ethical and social challenges this presents, particularly in the context of structural inequities and varied capacity in international research. Public involvement is essential to building locally responsive research policies, including on data sharing, but little research has involved stakeholders from low-to-middle income countries.

Methods

Between January and June 2014, a qualitative study was conducted in Kenya involving sixty stakeholders with varying experiences of research in a deliberative process to explore views on benefits and challenges in research data sharing. In-depth interviews and extended small group discussions based on information sharing and facilitated debate were used to collect data. Data were analysed using Framework Analysis, and charting flow and dynamics in debates.

Findings

The findings highlight both the opportunities and challenges of communicating about this complex and relatively novel topic for many stakeholders. For more and less research-experienced stakeholders, ethical research data sharing is likely to rest on the development and implementation of appropriate trust-building processes, linked to local perceptions of benefits and challenges. The central nature of trust is underpinned by uncertainties around who might request what data, for what purpose and when. Key benefits perceived in this consultation were concerned with the promotion of public health through science, with legitimate beneficiaries defined differently by different groups. Important challenges were risks to the interests of study participants, communities and originating researchers through stigmatisation, loss of privacy, impacting autonomy and unfair competition, including through forms of intentional and unintentional ''misuse'' of data. Risks were also seen for science.

Discussion

Given background structural inequities in much international research, building trust in this low-to-middle income setting includes ensuring that the interests of study participants, primary communities and originating researchers will be promoted as far as possible, as well as protected. Important ways of building trust in data sharing include involving the public in policy development and implementation, promoting scientific collaborations around data sharing and building close partnerships between researchers and government health authorities to provide checks and balances on data sharing, and promote near and long-term translational benefits.     

Virus evolution and transmission in an ever more connected world

The frequency and global impact of infectious disease outbreaks, particularly those caused by emerging viruses, demonstrate the need for a better understanding of how spatial ecology and pathogen evolution jointly shape epidemic dynamics. Advances in computational techniques and the increasing availability of genetic and geospatial data are helping to address this problem, particularly when both information sources are combined. Here, we review research at the intersection of evolutionary biology, human geography and epidemiology that is working towards an integrated view of spatial incidence, host mobility and viral genetic diversity. We first discuss how empirical studies have combined viral spatial and genetic data, focusing particularly on the contribution of evolutionary analyses to epidemiology and disease control. Second, we explore the interplay between virus evolution and global dispersal in more depth for two pathogens: human influenza A virus and chikungunya virus. We discuss the opportunities for future research arising from new analyses of human transportation and trade networks, as well as the associated challenges in accessing and sharing relevant spatial and genetic data.     

H3Africa: An Africa exemplar? Exploring its framework on protecting human research participants

The Human Heredity and Health in Africa (H3Africa) Consortium is a conglomeration of research and infrastructure projects spread throughout Africa whose aim is to apply genomic methodology to diseases affecting the people in the region. Its operation is innovative in the sense that it is doing something new; that is, filling a hitherto existing void in genomic research capability of African scientists and infusing resources and manpower to institutions and investigators across Africa. But aside from developing and sustaining capacity in genomic research and biorepositories, H3Africa is also invested in developing appropriate ethical regulatory regime to govern research in these areas. This latter concern –research ethics governance – is the major subject of this paper. Specifically, the paper discusses protection of research participants as envisaged by H3Africa in the area of consent, safeguarding privacy, maintaining confidentiality of health information and sharing of data/biospecimens. The ultimate goal is to determine whether H3Africa initiatives and processes are consistent or at odds with international guidelines and best practices.     

Mine, yours, ours? Sharing data on human genetic variation

The achievement of a robust, effective and responsible form of data sharing is currently regarded as a priority for biological and bio-medical research. Empirical evaluations of data sharing may be regarded as an indispensable first step in the identification of critical aspects and the development of strategies aimed at increasing availability of research data for the scientific community as a whole. Research concerning human genetic variation represents a potential forerunner in the establishment of widespread sharing of primary datasets. However, no specific analysis has been conducted to date in order to ascertain whether the sharing of primary datasets is common-practice in this research field. To this aim, we analyzed a total of 543 mitochondrial and Y chromosomal datasets reported in 508 papers indexed in the Pubmed database from 2008 to 2011. A substantial portion of datasets (21.9%) was found to have been withheld, while neither strong editorial policies nor high impact factor proved to be effective in increasing the sharing rate beyond the current figure of 80.5%. Disaggregating datasets for research fields, we could observe a substantially lower sharing in medical than evolutionary and forensic genetics, more evident for whole mtDNA sequences (15.0% vs 99.6%). The low rate of positive responses to e-mail requests sent to corresponding authors of withheld datasets (28.6%) suggests that sharing should be regarded as a prerequisite for final paper acceptance, while making authors deposit their results in open online databases which provide data quality control seems to provide the best-practice standard. Finally, we estimated that 29.8% to 32.9% of total resources are used to generate withheld datasets, implying that an important portion of research funding does not produce shared knowledge. By making the scientific community and the public aware of this important aspect, we may help popularize a more effective culture of data sharing.     

Molecular biology of bacterial methanol oxidation

Abstract A detailed understanding of the mechanism of methanol oxidation in bacteria is a prerequisite for the future construction of new strains carrying this trait, or the improvement of industrial processes which employ methylotrophic bacteria. Recent advances in the isolation of mutants and the characterization of cloned genes involved in C₁ metabolism have expanded the biochemical data obtained in previous years, and indirectly stimulate research on electron transport and bacterial oxidases. Due to the heterogeneity of the physiology and genetic background of methylotrophs, classical genetic techniques are not readily applicable. The adaptation of these methods requires a detailed understanding of both bacterial metabolism and the principles of the genetic techniques involved. The results obtained to date from a limited number of methylotrophic organisms, using recombinant techniques, may facilitate future research in other organisms that have proved refractory to classical genetic analysis.     

CEDAR: communication efficient distributed analysis for regressions

Electronic health records (EHRs) offer great promises for advancing precision medicine and, at the same time, present significant analytical challenges. Particularly, it is often the case that patient-level data in EHRs cannot be shared across institutions (data sources) due to government regulations and/or institutional policies. As a result, there are growing interests about distributed learning over multiple EHRs databases without sharing patient-level data. To tackle such challenges, we propose a novel communication efficient method that aggregates the optimal estimates of external sites, by turning the problem into a missing data problem. In addition, we propose incorporating posterior samples of remote sites, which can provide partial information on the missing quantities and improve efficiency of parameter estimates while having the differential privacy property and thus reducing the risk of information leaking. The proposed approach, without sharing the raw patient level data, allows for proper statistical inference. We provide theoretical investigation for the asymptotic properties of the proposed method for statistical inference as well as differential privacy, and evaluate its performance in simulations and real data analyses in comparison with several recently developed methods.     

Carbon footprint initiative in Uganda

Purpose

Substantial evidence from numerous studies indicate that Uganda is already experiencing the negative impacts attributed to climate change, manifested by changing and unpredictable weather patterns, with implications to food production, water, and livelihood. Therefore, reducing carbon footprints is a key ingredient in mitigating climate change. However, this requires availability of adequate knowledge and human resource capacities to analyze and manage the carbon dynamics as well as energy-related aspects at all levels of organizations. It is against this background that training activities were designed to equip participants with knowledge and skills on the subject of carbon footprints.

Results

Participants were exposed to current techniques and methods of estimating and reducing carbon footprints; and equipped with knowledge on pathways for realizing carbon neutral resilient systems. In addition, participants formed a carbon footprint network with a view of sharing experience with other actors elsewhere in this field, and periodically organize similar trainings and other avenues for experience and knowledge sharing.