Rise of the super-sized genome projects

Philippa Brice

25 August 2016

The UK’s 100,000 Genomes Project (100KGP), when announced in 2012, put existing efforts in the shade. Hitherto, efforts had begun with projects involving 1000 genomes, or at a push 10,000 genomes – ambitious targets at the time of proposal, especially given that the first human genome sequence took thirteen years and a massive international effort to complete, but soon eclipsed by new horizons, thanks to the ongoing technological developments in sequencing.

The first to break the fabled $1000 genome barrier pose d in 2004 as a goal was Illumina, with their ultra-high throughput HiSeq X Ten Sequencing System. The race to sequence genomes immediately accelerated, with the first customers being the US Broad Institute, the Australian Garvan Institute, and Genomics England itself, as the UK government struck a major deal with Illumina and the Wellcome Trust to build and equip a massive sequencing centre outside Cambridge, as part of a £300 million package to see 100,000 genomes sequenced by 2017.

Inevitably, the 100KGP would inspire other countries not only to emulate but to exceed the UK’s goals. Genomics England is reportedly collaborating with other initiatives in countries including Australia and Canada to assist their efforts, and offering to partner with others; according to Healthcare UK, ‘Few countries are so well prepared and many risk falling behind’. France recently revealed plans for a similar effort, including specific recommendations to engage with Genomics England, whilst the Genome Asia 100K aims to amass 100,000 genome s exclusively from Asian populations. 

From genomic to personalised medicine

However, the rapidly expanding field of personalised medicine has heralded a new phase in major genome projects, with president Obama’s much vaunted Precision Medicine Initiative (PMI) launched in 2015 with an initial budget of $215 million and plans to recruit a participant bank of at least a million people. 

Whilst earlier initiatives such as the UK Biobank project and the US Million Veteran Program (MVP) have created vast genomic databases – with half a million participants for the former and over halfway to the target million for the latter, which is said to be the largest genom ic database in the world at present – they did not set out to amass whole genome sequence data – rather, representative genotypic data.

In contrast, the PMI, frequently referred to as the ‘million genomes project’ has set its sights on a million whole genome sequences as a baseline target to underpin personalised medicine. Nor is it likely to rest there – US Food and Drug Administration

(FDA) lead Dr Robert Califf has reportedly called for 10 million, or even 100 million, as a target – perhaps spurred on by news of China’s $9.2 billion rival Precision Medicine Initiative, which aims to hit 100 million genomes by 2030. This rather puts in the shade global pharmaceutical company Astra Zeneca’s plans to create a database of 2 million patient genomes in partnership with the Sanger Institute and Human Longevity, though it should be noted that the link between number of genomes sequenced and effective personalised medicine solutions produced is by no means automatic.

A new entry to the million genomes club?

Most recently, the European Alliance for Personalized Medicine (EAPM) has called for a new project to link sequencing efforts across EU member states in a similar manner to the Genome Asia 100K, but to create a shared database of a million genomes from European populations for clinical research. Writing in the EU Reporter, EAPM Executive Director Denis Horgan says of the proposed Million European Genomes Alliance “if the US can pull off a project of such magnitude with its 300 million citizens then, surely, the EU can achieve the same with 500 million across 28 member states”. Plans for the UK to leave the EU could slow down the EAPM, if they prevent the expected 100,000 genomes from contributing to the total, but UK biomedical researchers will undoubtedly be keen to participate in such an ambitious project, if it takes off. Benefits are proposed to be not only improvements in health and reductions in health inequalities, but also stimulation of the European life sciences industry.

Slow progress

Meanwhile, back at the genome sequencing coalface, the 100,000 Genomes Project’s progress is markedly slower. Around 12,500 genomes have been completed so far, a total that presumably excludes the relatively tiny genomes from the mycobacteria that cause tuberculosis, which appear to form the main part of the infectious disease element of the project led by Public Health England.

Admittedly, it could hardly be expected that progress in actual genome sequencing could be paced evenly throughout the project; the first phase was to run until 2017, but this included building the sequencing centre and associated infrastructure from scratch, including creating the series of linked Genomic Medicine Centres to recruit project participants. Anyone who has ever seen a building project through will know that planning and laying the foundations takes longer than building the basic structure! 

With 2016 rapidly slipping away, the heat is on for Genomics England to deliver a lot of human genome sequences in a relatively short time, to keep pace not only with international rivals (the Garvan Institute is reportedly churning out 1,000 human genome sequences per month) but also home-grown ambitions. Plans for a specific Personalised Medicine Strategy  for NHS England led by Chief Scientific Officer Prof Sue Hill (expected to build firmly on the foundations of the 100,000 Genomes Project) continue to develop as the international hunger for the benefits of personalised medicine grows.