Genomic sequencing capacity, data retention, and personal access to raw data in Europe

Whole genome/exome sequencing (WGS/WES) has become widely adopted in research and, more recently, in clinical settings. Many hope that the information obtained from the interpretation of these data will have medical benefits for patients and—in some cases—also their biological relatives. Because of the manifold possibilities to reuse genomic data, enabling sequenced individuals to access their own raw (uninterpreted) genomic data is a highly debated issue. This paper reports some of the first empirical findings on personal genome access policies and practices. We interviewed 39 respondents, working at 33 institutions in 21 countries across Europe. These sequencing institutions generate massive amounts of WGS/WES data and represent varying organisational structures and operational models. Taken together, in total, these institutions have sequenced ∼317,259 genomes and exomes to date. Most of the sequencing institutions reported that they are able to store raw genomic data in compliance with various national regulations, although there was a lack of standardisation of storage formats. Interviewees from 12 of the 33 institutions included in our study reported that they had received requests for personal access to raw genomic data from sequenced individuals. In the absence of policies on how to process such requests, these were decided on an ad hoc basis; in the end, at least 28 requests were granted, while there were no reports of requests being rejected. Given the rights, interests, and liabilities at stake, it is essential that sequencing institutions adopt clear policies and processes for raw genomic data retention and personal access

Parental Access to Children's Raw Genomic Data in Canada: Legal Rights and Professional Responsibility

Children with rare and common diseases now undergo whole genome sequencing (WGS) in clinical and research contexts. Parents sometimes request access to their child's raw genomic data, to pursue their own analyses or for onward sharing with health professionals and researchers. These requests raise legal, ethical, and practical issues for professionals and parents alike. The advent of widespread WGS in pediatrics occurs in a context where privacy and data protection law remains focused on giving individuals control-oriented rights with respect to their personal information. Acting in their child's stead and in their best interests, parents are generally the ones who will be exercising these informational rights on behalf of the child. In this paper, we map the contours of parental authority to access their child's raw genomic data. We consider three use cases: hospital-based researchers, healthcare professionals acting in a clinical-diagnostic capacity, and “pure” academic researchers at a public institution. Our research seeks to answer two principal questions: Do parents have a right of access to their child's raw WGS data? If so, what are the limits of this right? Primarily focused on the laws of Ontario, Canada's most populous province, with a secondary focus on Canada's three other most populous provinces (Quebec, British Columbia, and Alberta) and the European Union, our principal findings include (1) parents have a general right of access to information about their children, but that the access right is more capacious in the clinical context than in the research context; (2) the right of access extends to personal data in raw form; (3) a consideration of the best interests of the child may materially limit the legal rights of parents to access data about their child; (4) the ability to exercise rights of access are transferred from parents to children when they gain decision-making capacity in both the clinical and research contexts, but with more nuance in the former. With these findings in mind, we argue that professional guidelines, which are concerned with obligations to interpret and return results, may assist in furthering a child's best interests in the context of legal access rights. We conclude by crafting recommendations for healthcare professionals in the clinical and research contexts when faced with a parental request for a child's raw genomic data

GA4GH: International policies and standards for data sharing across genomic research and healthcare.

The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution. We describe the GA4GH organization, which is fueled by the development efforts of eight Work Streams and informed by the needs of 24 Driver Projects and other key stakeholders. We present the GA4GH suite of secure, interoperable technical standards and policy frameworks and review the current status of standards, their relevance to key domains of research and clinical care, and future plans of GA4GH. Broad international participation in building, adopting, and deploying GA4GH standards and frameworks will catalyze an unprecedented effort in data sharing that will be critical to advancing genomic medicine and ensuring that all populations can access its benefits

Points-based physical activity: a novel approach to facilitate changes in body composition in inactive women with overweight and obesity

Background Physical activity (PA) interventions for the promotion of weight-management may benefit from increased choice and flexibility to overcome commonly-perceived barriers to PA. The aim of this study was to investigate the effects of a novel “points-based” approach to PA on body composition in inactive women, who are overweight or obese. Methods Seventy-six overweight or obese, inactive women were randomly allocated to one of three conditions: ‘Points-based’ PA (PBPA; 30 “PA points”•week− 1), Structured exercise (StructEx; 150 min moderate-intensity exercise•week− 1) or control (CONT; continue habitual inactive lifestyle) for a 24-week intervention. PA points for activities were adapted from MET values, and 30 points was equivalent to 150 min of brisk walking. Measures of body composition (dual-energy x-ray absorptiometry) and anthropometry were obtained at weeks 0, 4, 12 and 24. Self-report activities were recorded weekly, with objective measures of PA (tri-axial accelerometry) and self-report measures of food intake obtained at weeks 0 and 24. Results Fifty-eight women completed the study and provided data for primary outcomes. Of these, n = 41 and n = 19 provided data for food intake and objectively assessed PA. Mixed-design ANOVAs demonstrated that those in PBPA achieved a significant weight-loss at 24 weeks of − 3.3 ± 5.9 kg (− 3.4 ± 7.1%, p = 0.004). Waist circumference was reduced in PBPA at 24 weeks (− 2.8 ± 4.6 cm), compared with CONT (+ 2.1 ± 6.6 cm, p = 0.024). There was a trend for greater reductions in fat mass for those in PBPA vs. CONT (− 2.3 ± 4.6 kg vs. + 0.1 ± 2.0 kg, p = 0.075). Android fat was reduced in PBPA at both 12 weeks (− 6.1 ± 12.6%, p = 0.005) and 24 weeks (− 10.1 ± 18.4%, p = 0.005), while there was a trend for greater reductions in visceral adipose tissue in PBPA (− 5.8 ± 26.0%) vs. CONT at 24 weeks (+ 7.8 ± 18.3%, p = 0.053). Body composition, body weight and waist circumference were unchanged in StructEx. There were trends for increases in light-activity and reductions in sedentary time in PBPA. There was a trend for a reduction in daily energy intake of − 445 ± 564 kcal (p = 0.074), and a significant reduction in daily fat intake (p = 0.042) in PBPA. Conclusion A “points-based” approach to physical activity appears to be an effective strategy for inducing modest reductions in body weight and body fat in inactive women with overweight and obesity

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Registered access : a ‘Triple-A’ approach

We propose a standard model for a novel data access tier - registered access - to facilitate access to data that cannot be published in open access archives owing to ethical and legal risk. Based on an analysis of applicable research ethics and other legal and administrative frameworks, we discuss the general characteristics of this Registered Access Model, which would comprise a three-stage approval process: Authentication, Attestation and Authorization. We are piloting registered access with the Demonstration Projects of the Global Alliance for Genomics and Health for which it may provide a suitable mechanism for access to certain data types and to different types of data users

Toward better governance of human genomic data

Here, we argue that, in line with the dramatic increase in the collection, storage and curation of human genomic data for biomedical research, genomic data repositories and consortia have adopted governance frameworks to both enable wide access and protect against possible harms. However, the merits and limitations of different governance frameworks in achieving these twin aims are a matter of ongoing debate in the scientific community; indeed, best practices and points for consideration are notably absent in devising governance frameworks for genomic databases. According to our collective experience in devising and assessing governance frameworks, we identify five key functions of ‘good governance’ (or ‘better governance’) and three areas in which trade-offs should be considered when specifying policies within those functions. We apply these functions as a benchmark to describe, as an example, the governance frameworks of six large-scale international genomic projects

Who should have access to genomic data and how should they be held accountable? Perspectives of Data Access Committee members and experts

Facilitating the responsible access to genomic research data is an emerging ethical and scientific imperative. Data Access Committees (DACs) assess the ethical footing and scientific feasibility of the data access requests and evaluate the qualification of applicants to ensure they are bona fide researchers. Through semi-structured interviews, we explored the opinions and experiences of 20 DAC members and experts concerning the users' qualification criteria and mechanisms to hold users accountable. According to our respondents, such evaluation is necessary to ensure applicants are trustworthy, meet a certain level of expertise or experience and are aware of the rules and the associated concerns with genomic data sharing. The respondents noted, however, that the qualification criteria are fragmented or are poorly delineated at times. Thus, developing qualification criteria seems vital for an objective, fair and responsible access procedure. Similarly, the access review will benefit from using common ways of verifying the users' affiliations. Furthermore, some DAC members expressed concern over the uncertain oversight of downstream data use, in particular where data are shared across borders. DAC members and experts did not consider current sanctions and enforcement procedures to be crystal clear. Therefore, data sharing policies should address this gap by establishing proportionate sanctions both against data producers and data users' non-compliance. Users' home institutes will need to have an active role in keeping oversight on the downstream data uses, considering their ultimate responsibility if wrongdoings happen