A human rights approach to an international code of conduct for genomic and clinical data sharing

Fostering data sharing is a scientific and ethical imperative. Health gains can be achieved more comprehensively and quickly by combining large, information-rich datasets from across conventionally siloed disciplines and geographic areas. While collaboration for data sharing is increasingly embraced by policymakers and the international biomedical community, we lack a common ethical and legal framework to connect regulators, funders, consortia, and research projects so as to facilitate genomic and clinical data linkage, global science collaboration, and responsible research conduct. Governance tools can be used to responsibly steer the sharing of data for proper stewardship of research discovery, genomics research resources, and their clinical applications. In this article, we propose that an international code of conduct be designed to enable global genomic and clinical data sharing for biomedical research. To give this proposed code universal application and accountability, however, we propose to position it within a human rights framework. This proposition is not without precedent: international treaties have long recognized that everyone has a right to the benefits of scientific progress and its applications, and a right to the protection of the moral and material interests resulting from scientific productions. It is time to apply these twin rights to internationally collaborative genomic and clinical data sharing.     

DNAdigest and Repositive: Connecting the World of Genomic Data

There is no unified place where genomics researchers can search through all available raw genomic data in a way similar to OMIM for genes or Uniprot for proteins. With the recent increase in the amount of genomic data that is being produced and the ever-growing promises of precision medicine, this is becoming more and more of a problem. DNAdigest is a charity working to promote efficient sharing of human genomic data to improve the outcome of genomic research and diagnostics for the benefit of patients. Repositive, a social enterprise spin-out of DNAdigest, is building an online platform that indexes genomic data stored in repositories and thus enables researchers to search for and access a range of human genomic data sources through a single, easy-to-use interface, free of charge.     

Redefining Genomic Privacy: Trust and Empowerment

Fulfilling the promise of the genetic revolution requires the analysis of large datasets containing information from thousands to millions of participants. However, sharing human genomic data requires protecting subjects from potential harm. Current models rely on de-identification techniques in which privacy versus data utility becomes a zero-sum game. Instead, we propose the use of trust-enabling techniques to create a solution in which researchers and participants both win. To do so we introduce three principles that facilitate trust in genetic research and outline one possible framework built upon those principles. Our hope is that such trust-centric frameworks provide a sustainable solution that reconciles genetic privacy with data sharing and facilitates genetic research.     

Human genomes as email attachments

SUMMARY: The amount of genomic sequence data being generated and made available through public databases continues to increase at an ever-expanding rate. Downloading, copying, sharing and manipulating these large datasets are becoming difficult and time consuming for researchers. We need to consider using advanced compression techniques as part of a standard data format for genomic data. The inherent structure of genome data allows for more efficient lossless compression than can be obtained through the use of generic compression programs. We apply a series of techniques to James Watson's genome that in combination reduce it to a mere 4MB, small enough to be sent as an email attachment.     

Relationship between spatial organization and biological function,analyzed using gene ontology and chromosome conformation capture of human and fission yeast genomes

Cells regulate functionally related genes cis- and trans-contacts in order to perform specific biological roles. To understand the cryptic spatial genomic contexts underlying these biological functions, we analyzed the gene association data from the gene ontology (GO) database and the genomic spatial organization data obtained by analysis of chromosome conformation capture (3C)-based data from the Sequence Read Archive, where GO and 3C-based data were used to measure functional similarity and spatial proximity, respectively, between genomic loci. In the human genome and the fission yeast genome, we observed that correlation between the two measures was statistically significant on a genome-wide scale. Specifically, it is also confirmed that the genomic spatial architecture is affected by functional similarity of genes by showing better correlation of functional similarities with spatial distances estimated by contact frequencies than those estimated by genomic distances for cis-contacts. Furthermore, we analyzed distances between the genomic segments sharing the same GO term using the two-sample t test, found that the genomic segments identified by various GO terms are spatially located closer than the average distance over statistically-valid contacts, and provided a list of the GO terms. The results suggested that genomic loci with similar biological functions are situated in close proximity to each other in the nuclear space by aggregating functionally related genes in a short spatial range.     

Reconstruction of Microbial Haplotypes by Integration of Statistical and Physical Linkage in Scaffolding

DNA sequencing technologies provide unprecedented opportunities to analyze within-host evolution of microorganism populations. Often, within-host populations are analyzed via pooled sequencing of the population, which contains multiple individuals or “haplotypes.” However, current next-generation sequencing instruments, in conjunction with single-molecule barcoded linked-reads, cannot distinguish long haplotypes directly. Computational reconstruction of haplotypes from pooled sequencing has been attempted in virology, bacterial genomics, metagenomics, and human genetics, using algorithms based on either cross-host genetic sharing or within-host genomic reads. Here, we describe PoolHapX, a flexible computational approach that integrates information from both genetic sharing and genomic sequencing. We demonstrated that PoolHapX outperforms state-of-the-art tools tailored to specific organismal systems, and is robust to within-host evolution. Importantly, together with barcoded linked-reads, PoolHapX can infer whole-chromosome-scale haplotypes from 50 pools each containing 12 different haplotypes. By analyzing real data, we uncovered dynamic variations in the evolutionary processes of within-patient HIV populations previously unobserved in single position-based analysis.     

Share and share alike: deciding how to distribute the scientific and social benefits of genomic data

Emerging technologies make genomic analyses more efficient and less expensive, enabling genome-wide association and gene-environment interaction studies. In anticipation of their results, funding agencies such as the US National Institutes of Health and the Wellcome Trust are formulating guidelines for sharing the large amounts of genomic data that are generated by the projects that they sponsor. Data-sharing policies can have varying implications for how disease susceptibility and drug-response research will be pursued by the scientific community, and for who will benefit from the resulting medical discoveries. We suggest that the complex interplay of stakeholders and their interests, rather than single-issue and single-stakeholder perspectives, should be considered when deciding genomic data-sharing policies.     

Unpublished genomic data–how to share?

The field of genomics is often cited as the branch of biology that has led the way in data sharing. In most cases, sequencing data are made publicly available immediately after generation and often before the data generators have completed their analyses. Although the pros of such openness cannot be denied, problems can arise when unpublished genomic data are shared. In this editorial we touch on these issues and discuss the roles and responsibilities of the data generators, data users and journal editors.     

myKaryoView: a light-weight client for visualization of genomic data

The Distributed Annotation System (DAS) is a protocol for easy sharing and integration of biological annotations. In order to visualize feature annotations in a genomic context a client is required. Here we present myKaryoView, a simple light-weight DAS tool for visualization of genomic annotation. myKaryoView has been specifically configured to help analyse data derived from personal genomics, although it can also be used as a generic genome browser visualization. Several well-known data sources are provided to facilitate comparison of known genes and normal variation regions. The navigation experience is enhanced by simultaneous rendering of different levels of detail across chromosomes. A simple interface is provided to allow searches for any SNP, gene or chromosomal region. User-defined DAS data sources may also be added when querying the system. We demonstrate myKaryoView capabilities for adding user-defined sources with a set of genetic profiles of family-related individuals downloaded directly from 23andMe. myKaryoView is a web tool for visualization of genomic data specifically designed for direct-to-consumer genomic data that uses publicly available data distributed throughout the Internet. It does not require data to be held locally and it is capable of rendering any feature as long as it conforms to DAS specifications. Configuration and addition of sources to myKaryoView can be done through the interface. Here we show a proof of principle of myKaryoView's ability to display personal genomics data with 23andMe genome data sources. The tool is available at: http://mykaryoview.com.     

Patents and the human genome project--new claims for old?

The development and application of genomics is set to revolutionize the life sciences. Commercial exploitation of this research will allow the development of novel therapies and diagnostic assays. However, some argue that a 'gold rush' is underway and conflicts have already arisen over the question of filing patents and sharing data. In this article we consider some of the issues that relate to patenting genomic inventions.     

Intra-consortium data sharing in multi-national, multi-institutional genomic studies: gaps and guidance

Growing investments in health research by governments and charitable organizations have fueled an increase in collaborative research projects between investigators from affluent and developing countries. Current international guidelines are silent on common intra-consortium data-sharing issues that arise in the context of such collaborations. A lack of guidance on intra-consortium data sharing threatens to undermine the success of crucial research ventures. In this work we outline some of the practical problems commonly faced by investigators working in multi-institutional, international genomic collaborations and offer recommendations on these issues. A data sharing policy should be prospectively negotiated and concluded between collaborators as early as possible. Sponsors of research, including those from developing countries, should issue detailed guidance on the above and related issues as doing so will facilitate research and catalyze scientific progress.     

Controlled Access under Review: Improving the Governance of Genomic Data Access

In parallel with massive genomic data production, data sharing practices have rapidly expanded over the last decade. To ensure authorized access to data, access review by data access committees (DACs) has been utilized as one potential solution. Here we discuss core elements to be integrated into the fabric of access review by both established and emerging DACs in order to foster fair, efficient, and responsible access to datasets. We particularly highlight the fact that the access review process could be adversely influenced by the potential conflicts of interest of data producers, particularly when they are directly involved in DACs management. Therefore, in structuring DACs and access procedures, possible data withholding by data producers should receive thorough attention.     

FisOmics: A portal of fish genomic resources

An online portal, accessible at URL: http://mail.nbfgr.res.in/FisOmics/, was developed that features different genomic databases and tools. The portal, named as FisOmics, acts as a platform for sharing fish genomic sequences and related information in addition to facilitating the access of high-performance computational resources for genome and proteome data analyses. It provides the ability for quarrying, analysing and visualizing genomic sequences and related information. The featured databases in FisOmics are in the World Wide Web domain already. The aim to develop portal was to provide a nodal point to access the featured databases and work conveniently. Presently, FisOmics includes databases on barcode sequences, microsatellite markers, mitogenome sequences, hypoxia-responsive genes and karyology of fishes. Besides, it has a link to other molecular resources and reports on the on-going activities and research achievements.     

Convergent evolution of clustering of Iroquois homeobox genes across metazoans

Vertebrate and Drosophila Iroquois genes are organized in clusters of 3 genes sharing blocks of conserved regulatory sequences. Here, we report a 3-gene cluster in the basal, preduplicative chordate amphioxus. Surprisingly, however, the origin of the amphioxus cluster is independent of those in vertebrates and drosophilids. Investigation of genomic organization of Iroquois genes in other 17 metazoan genomes revealed a fourth independent 3-gene cluster organization in polychaetes, as well as additional 2- and 4-gene clusters in other clades, in one of the most striking examples of convergence in genomic organization described so far. The recurrent independent evolution of Iroquois clusters suggests a functional importance of this organization for these genes, perhaps related to the sharing of regulatory elements. Consistent with this, comparative analysis of genomic regions flanking the 3 amphioxus Irx genes revealed several blocks of sequences, conserved for at least 100 Myr. Finally, we discuss the possible causes and implications of the convergent evolution of this genomic and regulatory organization throughout metazoans.     

The temporal distribution of gene duplication events in a set of highly conserved human gene families

Using a data set of protein translations associated with map positions in the human genome, we identified 1520 mapped highly conserved gene families. By comparing sharing of families between genomic windows, we identified 92 potentially duplicated blocks in the human genome containing 422 duplicated members of these families. Using branching order in the phylogenetic trees, we timed gene duplication events in these families relative to the primate-rodent divergence, the amniote-amphibian divergence, and the deuterostome-protostome divergence. The results showed similar patterns of gene duplication times within duplicated blocks and outside duplicated blocks. Both within and outside duplicated blocks, numerous duplications were timed prior to the deuterostome-protostome divergence, whereas others occurred after the amniote-amphibian divergence. Thus, neither gene duplication in general nor duplication of genomic blocks could be attributed entirely to polyploidization early in vertebrate history. The strongest signal in the data was a tendency for intrachromosomal duplications to be more recent than interchromosomal duplications, consistent with a model whereby tandem duplication-whether of single genes or of genomic blocks-may be followed by eventual separation of duplicates due to chromosomal rearrangements. The rate of separation of tandemly duplicated gene pairs onto separated chromosomes in the human lineage was estimated at 1.7 x 10(-9) per gene-pair per year.     

Pathogenicity islands: the tip of the iceberg.

Pathogenicity islands represent distinct genetic elements encoding virulence factors of pathogenic bacteria. Pathogenicity islands belong to the class of genomic islands, which are common genetic elements sharing a set of unifying features. Genomic islands have been acquired by horizontal gene transfer. In recent years many different genomic islands have been discovered in a variety of pathogenic as well as non-pathogenic bacteria. Because they promote genetic variability, genomic islands play an important role in microbial evolution.     

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.     

A Nonparametric Test Reveals Selection for Rapid Flowering in the Arabidopsis Genome

The detection of footprints of natural selection in genetic polymorphism data is fundamental to understanding the genetic basis of adaptation, and has important implications for human health. The standard approach has been to reject neutrality in favor of selection if the pattern of variation at a candidate locus was significantly different from the predictions of the standard neutral model. The problem is that the standard neutral model assumes more than just neutrality, and it is almost always possible to explain the data using an alternative neutral model with more complex demography. Today's wealth of genomic polymorphism data, however, makes it possible to dispense with models altogether by simply comparing the pattern observed at a candidate locus to the genomic pattern, and rejecting neutrality if the pattern is extreme. Here, we utilize this approach on a truly genomic scale, comparing a candidate locus to thousands of alleles throughout the Arabidopsis thaliana genome. We demonstrate that selection has acted to increase the frequency of early-flowering alleles at the vernalization requirement locus FRIGIDA. Selection seems to have occurred during the last several thousand years, possibly in response to the spread of agriculture. We introduce a novel test statistic based on haplotype sharing that embraces the problem of population structure, and so should be widely applicable.     

A Nonparametric Test Reveals Selection for Rapid Flowering in the Arabidopsis Genome

The detection of footprints of natural selection in genetic polymorphism data is fundamental to understanding the genetic basis of adaptation, and has important implications for human health. The standard approach has been to reject neutrality in favor of selection if the pattern of variation at a candidate locus was significantly different from the predictions of the standard neutral model. The problem is that the standard neutral model assumes more than just neutrality, and it is almost always possible to explain the data using an alternative neutral model with more complex demography. Today's wealth of genomic polymorphism data, however, makes it possible to dispense with models altogether by simply comparing the pattern observed at a candidate locus to the genomic pattern, and rejecting neutrality if the pattern is extreme. Here, we utilize this approach on a truly genomic scale, comparing a candidate locus to thousands of alleles throughout the Arabidopsis thaliana genome. We demonstrate that selection has acted to increase the frequency of early-flowering alleles at the vernalization requirement locus FRIGIDA. Selection seems to have occurred during the last several thousand years, possibly in response to the spread of agriculture. We introduce a novel test statistic based on haplotype sharing that embraces the problem of population structure, and so should be widely applicable.