Orchestrating differential data access for translational research: a pilot implementation.

BACKGROUND: Translational researchers need robust IT solutions to access a range of data types, varying from public data sets to pseudonymised patient information with restricted access, provided on a case by case basis. The reason for this complication is that managing access policies to sensitive human data must consider issues of data confidentiality, identifiability, extent of consent, and data usage agreements. All these ethical, social and legal aspects must be incorporated into a differential management of restricted access to sensitive data. METHODS: In this paper we present a pilot system that uses several common open source software components in a novel combination to coordinate access to heterogeneous biomedical data repositories containing open data (open access) as well as sensitive data (restricted access) in the domain of biobanking and biosample research. Our approach is based on a digital identity federation and software to manage resource access entitlements. RESULTS: Open source software components were assembled and configured in such a way that they allow for different ways of restricted access according to the protection needs of the data. We have tested the resulting pilot infrastructure and assessed its performance, feasibility and reproducibility. CONCLUSIONS: Common open source software components are sufficient to allow for the creation of a secure system for differential access to sensitive data. The implementation of this system is exemplary for researchers facing similar requirements for restricted access data. Here we report experience and lessons learnt of our pilot implementation, which may be useful for similar use cases. Furthermore, we discuss possible extensions for more complex scenarios.

International federation of genomic medicine databases using GA4GH standards.

We promote a shared vision and guide for how and when to federate genomic and health-related data sharing, enabling connections and insights across independent, secure databases. The GA4GH encourages a federated approach wherein data providers have the mandate and resources to share, but where data cannot move for legal or technical reasons. We recommend a federated approach to connect national genomics initiatives into a global network and precision medicine resource.

GA4GH Passport standard for digital identity and access permissions.

The Global Alliance for Genomics and Health (GA4GH) supports international standards that enable a federated data sharing model for the research community while respecting data security, ethical and regulatory frameworks, and data authorization and access processes for sensitive data. The GA4GH Passport standard (Passport) defines a machine-readable digital identity that conveys roles and data access permissions (called "visas") for individual users. Visas are issued by data stewards, including data access committees (DACs) working with public databases, the entities responsible for the quality, integrity, and access arrangements for the datasets in the management of human biomedical data. Passports streamline management of data access rights across data systems by using visas that present a data user's digital identity and permissions across organizations, tools, environments, and services. We describe real-world implementations of the GA4GH Passport standard in use cases from ELIXIR Europe, National Institutes of Health, and the Autism Sharing Initiative. These implementations demonstrate that the Passport standard has provided transparent mechanisms for establishing permissions and authorizing data access across platforms.

The Data Use Ontology to streamline responsible access to human biomedical datasets.

Human biomedical datasets that are critical for research and clinical studies to benefit human health also often contain sensitive or potentially identifying information of individual participants. Thus, care must be taken when they are processed and made available to comply with ethical and regulatory frameworks and informed consent data conditions. To enable and streamline data access for these biomedical datasets, the Global Alliance for Genomics and Health (GA4GH) Data Use and Researcher Identities (DURI) work stream developed and approved the Data Use Ontology (DUO) standard. DUO is a hierarchical vocabulary of human and machine-readable data use terms that consistently and unambiguously represents a dataset's allowable data uses. DUO has been implemented by major international stakeholders such as the Broad and Sanger Institutes and is currently used in annotation of over 200,000 datasets worldwide. Using DUO in data management and access facilitates researchers' discovery and access of relevant datasets. DUO annotations increase the FAIRness of datasets and support data linkages using common data use profiles when integrating the data for secondary analyses. DUO is implemented in the Web Ontology Language (OWL) and, to increase community awareness and engagement, hosted in an open, centralized GitHub repository. DUO, together with the GA4GH Passport standard, offers a new, efficient, and streamlined data authorization and access framework that has enabled increased sharing of biomedical datasets worldwide.

Health expenditure, longevity, and child mortality: dynamic panel data approach with global data.

In this study, effects of public and private health expenditures on life expectancy at birth and infant mortality are analysed on a global scale with 195 countries in the years 1995-2014. The global data set is divided into country categories according to growth in life expectancy, decrease in infant mortality rate, and level of gross national income per capita. Some new dynamic panel model estimators, argued to be more efficient with high persistence series and predetermination compared to popular but complex GMM estimators, show that public health expenditures are generally more health-promoting than private expenditures. However, the health effects are not as great as primary education effects. Although the new estimators provide some new and valuable information on health expenditure effects on life expectancy and infant mortality on a global scale, they do not show desired robustness.

Publisher Correction: Federated discovery and sharing of genomic data using Beacons.

In the version of this article initially published, Lena Dolman's second affiliation was given as Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK. The correct second affiliation is Ontario Institute for Cancer Research, Toronto, Ontario, Canada. The error has been corrected in the HTML and PDF versions of the article.

Common ELIXIR Service for Researcher Authentication and Authorisation.

A common Authentication and Authorisation Infrastructure (AAI) that would allow single sign-on to services has been identified as a key enabler for European bioinformatics. ELIXIR AAI is an ELIXIR service portfolio for authenticating researchers to ELIXIR services and assisting these services on user privileges during research usage. It relieves the scientific service providers from managing the user identities and authorisation themselves, enables the researcher to have a single set of credentials to all ELIXIR services and supports meeting the requirements imposed by the data protection laws. ELIXIR AAI was launched in late 2016 and is part of the ELIXIR Compute platform portfolio. By the end of 2017 the number of users reached 1000, while the number of relying scientific services was 36. This paper presents the requirements and design of the ELIXIR AAI and the policies related to its use, and how it can be used for serving some example services, such as document management, social media, data discovery, human data access, cloud compute and training services.

Registered access: authorizing data access.

The Global Alliance for Genomics and Health (GA4GH) proposes a data access policy model-"registered access"-to increase and improve access to data requiring an agreement to basic terms and conditions, such as the use of DNA sequence and health data in research. A registered access policy would enable a range of categories of users to gain access, starting with researchers and clinical care professionals. It would also facilitate general use and reuse of data but within the bounds of consent restrictions and other ethical obligations. In piloting registered access with the Scientific Demonstration data sharing projects of GA4GH, we provide additional ethics, policy and technical guidance to facilitate the implementation of this access model in an international setting.

Nutritional status and muscle strength in patients with emphysema and severe alpha(1)-antitrypsin deficiency.

BACKGROUND: The association between emphysema and weight loss is well known. Severe alpha(1)-antitrypsin deficiency is an important risk factor for the development of emphysema. STUDY OBJECTIVE: To study nutritional status and muscle strength in patients with severe alpha(1)-antitrypsin deficiency and emphysema. METHODS: Fifteen alpha(1)-antitrypsin-deficient patients with emphysema (7 men) and 18 healthy control subjects (9 men) were included in the study. Total body protein (TBP) was measured by in vivo neutron activation analysis of nitrogen. Lean body mass (LBM) was estimated from measurement of total body potassium. In analogy with body mass index (BMI), TBP index and LBM index were calculated as TBP/height squared and LBM/height squared, respectively. Respiratory muscle strength was studied by maximal inspiratory pressure (PImax) and maximal expiratory pressure (PEmax), and skeletal muscle strength by handgrip test. Plasma albumin, transthyretin, and retinol-binding protein concentrations were analyzed as biochemical markers of nutritional status. RESULTS: In the alpha(1)-antitrypsin-deficient individuals, lung function test results were consistent with severe chronic airway obstruction, whereas the healthy control subjects had normal lung function. No significant differences were found in age, body weight, or BMI between the groups. TBP (p < 0.05), TBP index (p < 0.001), LBM index (p < 0.05), and plasma concentration of transthyretin (p < 0.01) were significantly lower in the patients than in the control subjects. There was a significant correlation between TBP and LBM (p < 0.001), and between TBP and body weight (p < 0.001). In the male subgroup, PImax (p < 0.05) and PEmax (p < 0.05) were significantly lower in the patients than in the control subjects. In the female subgroup, handgrip strength was significantly lower in the patients than in the control subjects (p < 0.05). Body weight was significantly correlated with handgrip test (p < 0.05) in the male patients. In the female patients, body weight was significantly correlated with PImax (p < 0.05), LBM with PEmax (p < 0.05), and LBM with handgrip test (p < 0.01). CONCLUSION: Reduced TBP and plasma transthyretin concentration in alpha(1)-antitrypsin-deficient patients with emphysema may indicate early signs of malnutrition.