The mission of HGP2 will be to empower all of humanity to read and use the knowledge of their genomes to lead healthier and longer lives. HGP2 will set initial goals covering data generation, precision intervention, and clinical translation:

Data generation goals

Sequence the genomes of > 1% of the world population with maximal genetic representation (80 M individuals from > 100 countries);

Contribute 50,000 telomere-to-telomere (T2T) phased diploid reference genomes from > 20 countries to a Human Pangenome Project and expand the pangenome reference to cover most diversity;

Define standards and methodologies for integrating multi-omics into precision medicine, and;

Create large multi-omics cohorts totaling > 0.1% of the world population from diverse populations and collect their multi-omics data (8 M individuals from > 10 countries).

Precision intervention goals

Define clinically actionable reporting and intervention best practices for carrier screening, incidental findings, dominant disorders, rare disease diagnosis, and pharmacogenomics;

Implement clinically actionable reporting and intervention for all genomes sequenced within the scope of HGP2, and;

Implement standardized health economics studies incorporating all genomes sequenced within the scope of HGP2, quantifying cost-effectiveness of genome-guided interventions.

Clinical translation goals

Catalog all genetic and multi-omic variation from genomes sequenced in HGP2;

Clarify the clinical relevance of all genetic and multi-omic variation cataloged, and;

Embed genomic and multi-omic findings into standard clinical practice and precision public health.

To achieve these goals, HGP2 is proposed to be organized to directly address key global challenges for precision public health:

Addressing economic challenge

HGP2 is proposed to be supported by an open industry pledge, where any company with relevant technologies or solutions participate by pledging low costs for the scale of HGP2’s goals. We propose a commitment to a $99 or less re-sequenced genome for HGP2, as well as significant in-kind contribution toward 1000 de novo T2T reference assemblies for each participating national initiative. HGP2 will organize an international funding initiative or institution to be a “World Bank” for LMICs participating in HGP2. These measures address global inequity, leveling the economic playing field for countries so that all may bring the scale and representation needed for the HGP2 effort. A health economics work stream will be established to integrate, assess, and share global study experiences. This will support HGP2’s participating countries with their health economics analysis and simulations, informing them on economic feasibility and value proposition. Most funding for HGP2 will come from existing and future national initiative budgets, which will be deployed more efficiently and create more value within the HGP2 framework. HGP2 will also work with international bodies such as the World Health Organization (WHO) and United Nations Sustainable Development Goals (UNSDGs) for funding support.

Addressing organizational challenge

As HGP2 is a global endeavor touching all of humanity, a national initiative participatory framework will help countries to coalesce around their common cause. This framework will be a national blueprint for precision public health, as well as provide access to HGP2 industry support, funding aid, standards, best practices, and scientific leadership. It will be equitable, interoperable, and public health outcomes oriented. Most of all, the HGP2 participatory framework will allow national initiatives to partake in something greater; through the HGP2 platform, national initiatives concurrently build a better country and a better world. Both ongoing and new national initiatives may join HGP2 through this participatory framework, in grassroot fashion. A global ELSI work stream comprised of representatives from participating countries or organizations will be established, pioneering new guidelines to preemptively protect the individual and serve as a watchdog for the responsible ethical use of data throughout HGP2.

Addressing infrastructural challenge

Global Alliance for Genomics and Health (GA4GH) is a choice platform to bridge the infrastructural challenge with its many interoperability standards, work streams, and driver projects underway. HGP2 may join the GA4GH community as a premier driver project and utilize their data interoperability, federation, analysis, and security standards. HGP2 could contribute to existing GA4GH work streams and other driver projects, as well as create new ones with GA4GH, particularly in data security. With the GA4GH backbone and community, the HGP2 national initiative participatory framework will better break down regional silos, enhance global collaboration, and translate global scientific discovery to public health outcomes.

Addressing scientific challenge

HGP2 will create a global research alliance to achieve its translational scientific goals and to foster knowledge equity among national initiative scientific strategies. Redundant effort must be avoided, when possible, to provide maximal support for existing scientific initiatives; this research alliance will foster “team science”, not competition. The HGP2 global research alliance will provide a participatory framework for scientific initiatives to access more interoperable data and resources to achieve their aims, in solidarity with the HGP2 mission.

Addressing ELSI challenge

HGP2 stakeholders will engage ELSI experts to develop culturally sensitive, respectful to human rights and, legally sound approaches for all humanity. Training core expertise in genomics and counselling — such as clinical geneticists, counsellors, and social workers — will be prioritized. Working with governments, regional groups, patient representative groups and genomics organizations will be of immense importance. International bodies such as WHO and UNESCO could be partners to ensure that ELSI are incorporated into government policies. Public announcements and universal declarations on these issues must be made by these august bodies, so that they become official policies in all member countries. Hence, similar to the original HGP, a specific budget will be allocated to address these ELSI challenges to ensure their solution.