20 July 2021

How a next generation Human Genome Project could save countless lives

By Saloni Dattani & Henry Fingerhut

There’s a quiet revolution underway in the biomedical sciences. The cost of sequencing a human genome has fallen by an estimated 10,000 times in the last 15 years. New gene therapies and immunotherapies, which are growing rapidly, are now able to target specific disease-associated genes and proteins with extraordinary precision. Algorithms able to predict the structure of proteins from their sequences alone have reached the same accuracy as equivalent research carried out by careful experimental methods.

Our ability to understand the structures of genes and proteins at such a precise level is slowly being translated into improvements in many aspects of human health. Sequencing can enable doctors to diagnose genetic disorders at birth and potentially provide life-saving treatment. And the development of specific antibodies has demonstrably reduced the illness faced by patients with various cancers and immune disorders. Antibody therapies are now being successfully used to treat coronary heart disease, which is estimated to be the leading cause of death worldwide. This progress would not have been possible without the genetic studies that identified specific proteins that were commonly disrupted in families with these diseases.

Research will undoubtedly uncover even more potential therapeutics, but scientists face a number of obstacles. The genes responsible for various diseases are tricky to identify and the mechanisms by which they cause disease are difficult to decipher. A key problem is that we lack complete data from different biological sources in the same patients, such as their DNA, gene expression, biomolecules and samples of damaged tissues. Without these, it is more challenging to understand how disease develops at a molecular level, and so we have fewer options in terms of where we can target treatment. Solving this is one major goal of multi-omics, which incorporates data from various layers of omics (i.e. genomics, transcriptomics, proteomics, metabolomics, and so on) to understand how these cogs interact with each other and regulate the human body.

For years, multi-omics research has faced several major roadblocks.

  1. Collection: It has been difficult to acquire multi-omics data for sufficiently large samples, due to the cost of the technologies involved. Omics studies measure thousands of biomolecules and biomarkers, making it crucial to have large numbers of participants to avoid being misled by chance differences in some of these biomolecules.

  2. Standardisation: It has been difficult to standardise the data that has been collected. Most multi-omics research comes from pooling together data from different types of omics or is limited to data from particular organs and tissues only. These multiple sources often mean there are large differences in the conditions under which data are collected, prepared, stored and measured, which have to be accounted for by researchers.

  3. Aggregation and Collaboration: There are currently only a few centralised repositories available that aggregate multi-omics data, and there is a lack of collaboration or sharing of best practices between researchers who work with the different types of omics data.

In combination, these constraints reveal the enormous benefits that would arise from a large-scale effort to collect and share multi-omics data from a consistent set of patients and biological samples, with a high degree of curation and standardisation. Given the falling costs of biomedical research and the successes of other collaborative efforts to collect biological data – many of which were established in the UK – the benefits of developing a multi-omics project at a national level are clear. This is the motivation for establishing a multi-omics research centre, Omics UK, that would be the next step in an ambitious agenda for public research in the biomedical sciences.

There is precedent in the new era of biomedical research ushered in in recent decades. The Human Genome Project, for example, was a moonshot programme that successfully identified and sequenced the whole human genome. The project was notable not only for the scientific advances at its core but also for the scale of international collaboration it involved, the new public-sector structures that were developed to support it, and the principles that were pioneered to enable large scale data sharing between researchers. Together, these features strengthened coordination between researchers, ensured that data was curated to a high level of quality, and protected the genome from being monopolised by private patents.

Building on this success, the biomedical community extended their ambitions to fully map comprehensive libraries of other important biomolecules. Just as the Human Genome Project mapped the entire set of human genes, the Human Proteome Project is set to map all proteins encoded by  genes and the Human Epigenome Project to map physical markers that regulate the expression of genes. They have already shown rapid success, with the Human Proteome Project mapping 90% of the Human proteome in just ten years. Once more, they have brought together academic and government research organisations across borders, including the UK’s Wellcome Sanger Institute, the private company Epigenomics AG, and France’s National Centre for Genotyping.

These projects lay the foundations for advances in the future of applied biomedicine. With maps of the genome, proteome, and epigenome in hand, researchers will be able to more easily identify biomarkers for disease and design targeted treatments. In the UK, several programmes have been organised to use these tools to advance precision medicine in the coming years. The ambitious Genome UK programme comprises the 100,000 Genomes Project, which carries out large scale genotyping, and the NHS Genomic Medicine Service, which sequences the genomes of patients and DNA from cancer cells as part of routine care providing data that researchers could use to develop targeted cell and gene therapies.

Multi-omics research is the next step, enabling researchers to uncover the connections among the genome, biomolecules, cellular processes and the broader environment, in both healthy and diseased contexts.

Omics UK would be a centre for this research: collating clinical data from patients and applying the foundational work carried out during the Human Proteome Project and Human Epigenome Project into knowledge to understand, predict and treat diseases. Most importantly, an Omics UK body would take a systems approach, uniting researchers in different fields of biomedical science, enabling data collection and sharing, as well as joint analysis to understand how distinct cellular structures and processes interact to affect disease. The UK Biobank has laid the basis for this important work, future-proofing against long-term research needs by collecting and storing biological samples that can be used not only to generate genomic data but crucially to also link genomics to hormone, metabolite and protein levels. Omics UK would provide a unifying structure and mission to carry out the multi-omic research enabled by the UK Biobank samples.

At its core, Omics UK would enable researchers from diverse areas to collaborate and share data with each other, with data governance practices that streamline the process. This would include curating biological samples to collect multi-omic assays, developing novel approaches to hosting and analysing multi-omic data, and building new tools and research methods on top of shared data, such as the Cancer Omics Atlas, a resource helping researchers to explore experimental targets across specialities.

The project would also translate research into targeted treatment and precision medicine by linking across sectors to biomedical companies. These links would be reciprocal, enabling researchers to examine high-quality practice data, to evaluate the effectiveness of treatments and identify new challenges.

Just 30 years on from the launch of the Human Genome Project, biomedical research has changed profoundly and our knowledge of the genome and proteome is already enabling scientists to develop targeted treatments to improve lives. Omics UK would be the next step in one of the most fruitful research enterprises of our time, bringing together scientists from disparate fields of biomedical research and building on comprehensive maps of the genome, proteome, and epigenome. It would advance our ability to treat clinical disease by connecting these layers of knowledge and translating them into practice, seizing the opportunities provided by this acceleration in biomedical sciences.

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Saloni Dattani is a PhD student in psychiatric genetics at King's College London. Henry Fingerhut is a Senior Policy Analyst in the Science & Innovation unit at the Tony Blair Institute for Global Change.

Columns are the author's own opinion and do not necessarily reflect the views of CapX.