Competing interests: digital health and indigenous data sovereignty.

Digital health is increasingly promoting open health data. Although this open approach promises a number of benefits, it also leads to tensions with Indigenous data sovereignty movements led by Indigenous peoples around the world who are asserting control over the use of health data as a part of self-determination. Digital health has a role in improving access to services and delivering improved health outcomes for Indigenous communities. However, we argue that in order to be effective and ethical, it is essential that the field engages more with Indigenous peoples´ rights and interests. We discuss challenges and possible improvements for data acquisition, management, analysis, and integration as they pertain to the health of Indigenous communities around the world.

Indigenous Peoples and research: self-determination in research governance.

Indigenous Peoples are reimagining their relationship with research and researchers through greater self-determination and involvement in research governance. The emerging discourse around Indigenous Data Sovereignty has provoked discussions about decolonizing data practices and highlighted the importance of Indigenous Data Governance to support Indigenous decision-making and control of data. Given that much data are generated from research, Indigenous research governance and Indigenous Data Governance overlap. In this paper, we broaden the concept of Indigenous Data Sovereignty by using the CARE Principles for Indigenous Data Governance to discuss how research legislation and policy adopted by Indigenous Peoples in the US set expectations around recognizing sovereign relationships, acknowledging rights and interests in data, and enabling Indigenous Peoples' participation in research governance.

Indigenous Peoples' Rights in Data: a contribution toward Indigenous Research Sovereignty.

Indigenous Peoples' right to sovereignty forms the foundation for advocacy and actions toward greater Indigenous self-determination and control across a range of domains that impact Indigenous Peoples' communities and cultures. Declarations for sovereignty are rising throughout Indigenous communities and across diverse fields, including Network Sovereignty, Food Sovereignty, Energy Sovereignty, and Data Sovereignty. Indigenous Research Sovereignty draws in the sovereignty discourse of these initiatives to consider their applications to the broader research ecosystem. Our exploration of Indigenous Research Sovereignty, or Indigenous self-determination in the context of research activities, has been focused on the relationship between Indigenous Data Sovereignty and efforts to describe Indigenous Peoples' Rights in data.

Extending the CARE Principles from tribal research policies to benefit sharing in genomic research.

Indigenous Peoples have historically been targets of extractive research that has led to little to no benefit. In genomics, such research not only exposes communities to harms and risks of misuse, but also deprives such communities of potential benefits. Tribes in the US have been exercising their sovereignty to limit this extractive practice by adopting laws and policies to govern research on their territories and with their citizens. Federally and state recognized tribes are in the strongest position to assert research oversight. Other tribes lack the same authority, given that federal and state governments do not recognize their rights to regulate research, resulting in varying levels of oversight by tribes. These governance measures establish collective protections absent from the US federal government's research oversight infrastructure, while setting expectations regarding benefits to tribes as political collectives. Using a legal epidemiology approach, the paper discusses findings from a review of Tribal research legislation, policy, and administrative materials from 26 tribes in the US. The discussion specifies issues viewed by tribes as facilitators and barriers to securing benefits from research for their nations and members/citizens, and describes preemptive and mitigating strategies pursued by tribes in response. These strategies are set within the framing of the CARE Principles for Indigenous Data Governance (Collective Benefit, Authority to Control, Responsibility, Ethics), a set of standards developed to ensure that decisions made about data pertaining to Indigenous communities at the individual and tribal levels are responsive to their values and collective interests. Our findings illustrate gaps to address for benefit sharing and a need to strengthen Responsibility and Ethics in tribal research governance.

Benefit sharing: Why inclusive provenance metadata matter.

Fair and equitable benefit sharing of genetic resources is an expectation of the Nagoya Protocol. Although the Nagoya Protocol does not yet formally apply to Digital Sequence Information ("DSI"), discussions are currently underway regarding to include such data through ongoing Convention on Biological Diversity ("CBD") negotiations. While Indigenous Peoples and Local Communities ("IPLC") expect the value generated from genomic data to be subject to benefit sharing arrangements, a range of views are currently being expressed by Nation States, IPLC and other stakeholders. The use of DSI gives rise to unique considerations, creating a gray area as to how it should be considered under the Nagoya Protocol's Access and Benefit Sharing ("ABS") principles. One way for benefit sharing to be enhanced is through the connection of data to proper provenance information. A significant development is the use of digital labeling systems to ensure that the origin of samples is appropriately disclosed. The Traditional Knowledge and Biocultural Labels initiative offers a practical option for data provided to genomic databases. In particular, the BioCultural Labels ("BC Labels") are a mechanism for Indigenous communities to identify and maintain provenance, origin and authority over biocultural material and data generated from Indigenous land and waters held in research, cultural institutions and data repositories. This form of cultural metadata adds value to the research endeavor and the creation of Indigenous fields within databases adds transparency and accountability to the research environment.

Two-eyed seeing: Embracing the power of Indigenous knowledge for a healthy and sustainable Ocean.

Indigenous knowledge is often disregarded and opportunities for positive change are lost. To protect the Ocean, a "two-eyed seeing" approach combining Indigenous and western knowledge systems can create advancements while empowering coastal Indigenous Peoples.

Using Indigenous Standards to Implement the CARE Principles: Setting Expectations through Tribal Research Codes.

Biomedical data are now organized in large-scale databases allowing researchers worldwide to access and utilize the data for new projects. As new technologies generate even larger amounts of data, data governance and data management are becoming pressing challenges. The FAIR principles (Findable, Accessible, Interoperable, and Reusable) were developed to facilitate data sharing. However, the Indigenous Data Sovereignty movement advocates for greater Indigenous control and oversight in order to share data on Indigenous Peoples' terms. This is especially true in the context of genetic research where Indigenous Peoples historically have been unethically exploited in the name of science. This article outlines the relationship between sovereignty and ethics in the context of data to describe the collective rights that Indigenous Peoples assert to increase control over their biomedical data. Then drawing on the CARE Principles for Indigenous Data Governance (Collective benefit, Authority to control, Responsibility, and Ethics), we explore how standards already set by Native nations in the United States, such as tribal research codes, provide direction for implementation of the CARE Principles to complement FAIR. A broader approach to policy and procedure regarding tribal participation in biomedical research is required and we make recommendations for tribes, institutions, and ethical practice.

Ethical, legal, and social issues in the Earth BioGenome Project.

The Earth BioGenome Project (EBP) is an audacious endeavor to obtain whole-genome sequences of representatives from all eukaryotic species on Earth. In addition to the project's technical and organizational challenges, it also faces complicated ethical, legal, and social issues. This paper, from members of the EBP's Ethical, Legal, and Social Issues (ELSI) Committee, catalogs these ELSI concerns arising from EBP. These include legal issues, such as sample collection and permitting; the applicability of international treaties, such as the Convention on Biological Diversity and the Nagoya Protocol; intellectual property; sample accessioning; and biosecurity and ethical issues, such as sampling from the territories of Indigenous peoples and local communities, the protection of endangered species, and cross-border collections, among several others. We also comment on the intersection of digital sequence information and data rights. More broadly, this list of ethical, legal, and social issues for large-scale genomic sequencing projects may be useful in the consideration of ethical frameworks for future projects. While we do not-and cannot-provide simple, overarching solutions for all the issues raised here, we conclude our perspective by beginning to chart a path forward for EBP's work.

Balancing openness with Indigenous data sovereignty: An opportunity to leave no one behind in the journey to sequence all of life.

The field of genomics has benefited greatly from its "openness" approach to data sharing. However, with the increasing volume of sequence information being created and stored and the growing number of international genomics efforts, the equity of openness is under question. The United Nations Convention of Biodiversity aims to develop and adopt a standard policy on access and benefit-sharing for sequence information across signatory parties. This standardization will have profound implications on genomics research, requiring a new definition of open data sharing. The redefinition of openness is not unwarranted, as its limitations have unintentionally introduced barriers of engagement to some, including Indigenous Peoples. This commentary provides an insight into the key challenges of openness faced by the researchers who aspire to protect and conserve global biodiversity, including Indigenous flora and fauna, and presents immediate, practical solutions that, if implemented, will equip the genomics community with both the diversity and inclusivity required to respectfully protect global biodiversity.

The founding charter of the Omic Biodiversity Observation Network (Omic BON).

Omic BON is a thematic Biodiversity Observation Network under the Group on Earth Observations Biodiversity Observation Network (GEO BON), focused on coordinating the observation of biomolecules in organisms and the environment. Our founding partners include representatives from national, regional, and global observing systems; standards organizations; and data and sample management infrastructures. By coordinating observing strategies, methods, and data flows, Omic BON will facilitate the co-creation of a global omics meta-observatory to generate actionable knowledge. Here, we present key elements of Omic BON's founding charter and first activities.

Empowering Equitable Data Use Partnerships and Indigenous Data Sovereignties Amid Pandemic Genomics.

The COVID-19 pandemic has inequitably impacted Indigenous communities in the United States. In this emergency state that highlighted existing inadequacies in US government and tribal public health infrastructures, many tribal nations contracted with commercial entities and other organization types to conduct rapid diagnostic and antibody testing, often based on proprietary technologies specific to the novel pathogen. They also partnered with public-private enterprises on clinical trials to further the development of vaccines. Indigenous people contributed biological samples for assessment and, in many cases, broadly consented for indefinite use for future genomics research. A concern is that the need for crisis aid may have placed Indigenous communities in a position to forego critical review of data use agreements by tribal research governances. In effect, tribal nations were placed in the unenviable position of trading short-term public health assistance for long-term, unrestricted access to Indigenous genomes that may disempower future tribal sovereignties over community members' data. Diagnostic testing, specimen collection, and vaccine research is ongoing; thus, our aim is to outline pathways to trust that center current and future equitable relationship-building between tribal entities and public-private interests. These pathways can be utilized to increase Indigenous communities' trust of external partners and share understanding of expectations for and execution of data protections. We discuss how to navigate genomic-based data use agreements in the context of pathogen genomics. While we focus on US tribal nations, Indigenous genomic data sovereignties relate to global Indigenous nations regardless of colonial government recognition.

Considerations for Cardiovascular Genetic and Genomic Research With Marginalized Racial and Ethnic Groups and Indigenous Peoples: A Scientific Statement From the American Heart Association.

Historically marginalized racial and ethnic groups and Indigenous peoples are burdened by significant health inequities that are compounded by their underrepresentation in genetic and genomic research. Of all genome-wide association study participants, ≈79% are of European descent, despite this group constituting only 16% of the global population. For underrepresented populations, polygenic risk scores derived from these studies are less accurate in predicting disease phenotypes, novel population-specific genetic variations may be misclassified as potentially pathogenic, and there is a lack of understanding of how different populations metabolize drugs. Although inclusion of marginalized racial and ethnic groups and Indigenous peoples in genetic and genomic research is crucial, scientific studies must be guided by ethical principles of respect, honesty, justice, reciprocity, and care for individuals and communities. Special considerations are needed to support research that benefits the scientific community as well as Indigenous peoples and marginalized groups. Before a project begins, collaboration with community leaders and agencies can lead to successful implementation of the study. Throughout the study, consideration must be given to issues such as implications of informed consent for individuals and communities, dissemination of findings through scientific and community avenues, and implications of community identity for data governance and sharing. Attention to these issues is critical, given historical harms in biomedical research that marginalized groups and Indigenous peoples have suffered. Conducting genetic and genomic research in partnership with Indigenous peoples and marginalized groups guided by ethical principles provides a pathway for scientific advances that will enhance prevention and treatment of cardiovascular disease for everyone.

Creating space for Indigenous perspectives on access and benefit-sharing: Encouraging researcher use of the Local Contexts Notices.

A recent Molecular Ecology editorial made a proactive statement of support for the "Nagoya Protocol" and the principle of benefit-sharing by requiring authors to provide a "Data Accessibility and Benefit-Sharing Statement" in their articles. Here, we encourage another step that enables Indigenous communities to provide their own definitions and aspirations for access and benefit-sharing alongside the author's "Statement". We invite the Molecular Ecology research community to use Biocultural-, Traditional Knowledge-, and Cultural Institution Notices to help Indigenous communities gain visibility within our research structures. Notices are one of the tools offered by the Biocultural Labels Initiative (part of the Local Contexts system) designed specifically for researchers and institutions. The Notices are highly visible, machine-readable icons that signal the Indigenous provenance of genetic resources, and rights of Indigenous communities to define the future use of genetic resources and derived benefits. The Notices invite collaboration with Indigenous communities and create spaces within our research systems for them to define the provenance, protocols, and permissions associated with genetic resources using Labels. Authors contributing to Molecular Ecology can apply Notices to their articles by providing the persistent unique identifier and an optional use-statement associated with the Notice in their "Data Accessibility and Benefit-Sharing Statement". In this way, our research community has an opportunity to accelerate support for the principles of the Nagoya Protocol, to alleviate concerns regarding Indigenous Data Sovereignty and equitable outcomes, and to build better relationships with Indigenous collaborators to enhance research, biodiversity, and conservation outcomes.

Including Digital Sequence Data in the Nagoya Protocol Can Promote Data Sharing.

The Nagoya Protocol (NP), a legal framework under the Convention on Biological Diversity (CBD), formalises fair and equitable sharing of benefits arising from biological diversity. It encompasses biological samples and associated indigenous knowledge, with equitable return of benefits to those providing samples. Recent proposals that the use of digital sequence information (DSI) derived from samples should also require benefit-sharing under the NP have raised concerns that this might hamper research progress. Here, we propose that formalised benefit-sharing for biological data use can increase willingness to participate in research and share data, by ensuring equitable collaboration between sample providers and researchers, and preventing exploitative practices. Three case studies demonstrate how equitable benefit-sharing agreements might build long-term collaborations, furthering research for global benefits.

Barriers and Considerations for Diagnosing Rare Diseases in Indigenous Populations.

Advances in omics and specifically genomic technologies are increasingly transforming rare disease diagnosis. However, the benefits of these advances are disproportionately experienced within and between populations, with Indigenous populations frequently experiencing diagnostic and therapeutic inequities. The International Rare Disease Research Consortium (IRDiRC) multi-stakeholder partnership has been advancing toward the vision of all people living with a rare disease receiving an accurate diagnosis, care, and available therapy within 1 year of coming to medical attention. In order to further progress toward this vision, IRDiRC has created a taskforce to explore the access barriers to diagnosis of rare genetic diseases faced by Indigenous peoples, with a view of developing recommendations to overcome them. Herein, we provide an overview of the state of play of current barriers and considerations identified by the taskforce, to further stimulate awareness of these issues and the passage toward solutions. We focus on analyzing barriers to accessing genetic services, participating in genomic research, and other aspects such as concerns about data sharing, the handling of biospecimens, and the importance of capacity building.

Indigenous Genomic Databases: Pragmatic Considerations and Cultural Contexts.

The potential to grow genomic knowledge and harness the subsequent clinical benefits has escalated the building of background variant databases (BVDs) for genetic diagnosis across the globe. Alongside the upsurge of this precision medicine, potential benefits have been highlighted for both rare genetic conditions and other diagnoses. However, with the ever-present "genomic divide," Indigenous peoples globally have valid concerns as they endure comparatively greater health disparities but stand to benefit the least from these novel scientific discoveries and progress in healthcare. The paucity of Indigenous healthcare providers and researchers in these fields contributes to this genomic divide both in access to, and availability of culturally safe, relevant and respectful healthcare using this genetic knowledge. The vital quest to provide equitable clinical research, and provision and use of genomic services and technologies provides a strong rationale for building BVDs for Indigenous peoples. Such tools would ground their representation and participation in accompanying genomic health research and benefit acquisition. We describe two, independent but highly similar initiatives-the "Silent Genomes" in Canada and the "Aotearoa Variome" in New Zealand-as exemplars that have had to address the aforementioned issues and work to create Indigenous BVDs with these populations. Taking into account the baseline inequities in genomic medicine for Indigenous populations and the ongoing challenges of implementing genomic research with Indigenous communities, we provide a rationale for multiple changes required that will assure communities represented in BVDs, as well as Indigenous researchers, that their participation will maximize benefits and minimize risk.