What does UK Biobank’s Pharma Proteomics election of Olink + Ultima Genomics NGS mean for proteomics researchers, and for the wider genomics community? Does it create a new Olink monopoly on NGS-proteommics? And what’s the impact on NGS technology providers?

At the end of last week the UK Biobank announced the full-scale launch of the UK Biobank Pharma Proteomics Project. This is slated to be the world’s most comprehensive study of circulating proteins, aiming to transform disease research and therapeutic development. This ambitious project, supported by 14 leading biopharmaceutical companies through the UK Biobank Pharma Proteomics Project (UKB-PPP), plans to analyze over 5,400 proteins in blood samples from half a million participants (it includes 100,000 follow-up samples taken up to 15 years later). By enabling researchers to study how protein levels change over time, this unprecedented dataset will shed light on the biological mechanisms underpinning disease progression and aging.

The project represents a milestone in population proteomics, a rapidly emerging field that investigates protein abundance and its role in diseases. UK Biobank’s pilot study, see Sun et al 2023, analyzed nearly 3,000 proteins in 54,000 participants and led to the discovery of over 14,000 genetic links to altered protein levels. Findings from this pilot have already advanced understanding of diseases such as breast cancer, cardiovascular disease, and neurodegenerative conditions like Parkinson’s. The full proteomics dataset, expected by 2027, promises to accelerate the discovery of biomarkers, enhance disease prediction, and support the development of targeted treatments.

The proteomics data will be integrated with UK Biobank’s existing datasets, including whole-genome sequencing and MRI imaging from nearly 100,000 participants. This layered approach will offer a detailed understanding of disease mechanisms and could drive the development of personalized medicine. By examining changes in protein levels alongside genetic and imaging data, researchers will gain unique insights into age-related conditions, neglected diseases like polycystic ovary syndrome, and complex illnesses such as motor neurone disease.

UK Biobank’s proteomics initiative highlights the importance of large-scale collaborations in modern medical research. The dataset will initially be accessible exclusively to the funding consortium for nine months before being made available to global researchers. This model ensures that discoveries are shared widely, fostering innovation across academia and industry.

As UK Biobank seeks additional funding to complete the full cohort analysis, the proteomics project represents a cornerstone effort in unlocking the molecular drivers of disease, paving the way for a new era in health research. This initiative not only underscores the growing importance of proteomics but also sets a benchmark for population-scale studies in the post-genomics era.

Breaking one technology monopoly to start another?

Central to this endeavor are cutting-edge technologies. Proteomic analysis will be conducted using Thermo Fisher Scientific’s Olink® Explore HT platform, which enables deep protein profiling, paired with Ultima Genomics’ UG 100™ sequencing technology. The sequencing will be performed at Regeneron Genetics Center, highlighting the project’s high-throughput capabilities. The collaboration underscores a significant shift in the next-generation sequencing (NGS) landscape, with Thermo Fisher and Ultima emerging as key players. And, ironically, might signal a push towards one technology ganing a monopoly.

Illumina has been dominating in NGS for ever, specifically short-read but they are still trying to get in on the long-read game. But recently there’s been a flurry of new companies coming to challenge this short-read dominance: Element Bio, Singular Genomics, Ultima Genomics, PacBio (Onso) and even, at a stretch, Nanopore’s Short Fragment Mode. This is finally breaking Illumina’s stranglehold on the NGS space and was perhaps most humorously highlighted by Dan Landau in his “Thanks to Ultima Genomics and BGI for delivering the much awaited
Illumina $200 genome”
Tweet!

However, the selection of Olink (Thermo Fisher) as opposed to SomaLogic (Illumina Protein Prep), for the proteomic analysis across the full 600,000 sample set in UK BioBank might mean this technology comes to dominate the space. Maybe not quite in the same way Illumina dominated NGS for almost 20 years, but as UKB becomes perhaps the dataset to benchmark against it could spell trouble ahead for SomaLogic (and other protein platforms – if you want to know more about Protein sequencing check out Albert Vilella’s substack (referral link)).

And given that at least one recent preprint (Rooney et al medRxiv) is highlighting the improved precision of SomaScan over Olink (CV of 6.8% versus 35.7% respectively) might the dominance given to Olink by UK BioBank prevent a “better” technology (by one measure) from becoming the leader?

A big win for Ultima Genomics…and a loss for Illumina

The data for the project will be generated Ultima Genomics UG 100 sequencer, which, as I said earlier, underscores a significant shift in the NGS landscape driven by transformative economics.

Firstly, this project announcement validates the Ultima technology for counting applications like single-cell and spatial, both of which are limited by costs if we want to drive data generation for AI & ML tools.

Secondly, it puts Ultima in the headlights for pharma as bona fide sequencing technology provider.

Thirdly, it probably opens the door for the next generation of population genomics studies to be done on a non-Illumina platform: Genomics England was done on Illumina (although Cancer 2.0 is being done on ONT), as were the All Of Us Research Program, the Million Veteran Program, and the Emirati Genome Programme (although the latter project had early data generated on BGI with M42 switching to Illumina for some data).

Fourthly, the 2nd wave of massive genomics initiatives coming with newborn screening opens a huge opportunity that will be driven by the promise $100 genome e.g. GUARDIAN’s (Genomic Uniform-screening Against Rare Diseases in All Newborns) goal of sequencing 100,000 newborns; Genomics England Newborn Genomes Programme, Screen4Care in Europe (sorry about Brexit) and likely projects in China (see Chen 2023 panel NGS paper) Australia, New Zealand, Korea, Taiwan, and Qatar.

Fifthlythe least well pressure tested of my points so be careful with it – this project might put Ultima in the spotlight for companies like Natera, Foundation Medicine, Guardant Health, Personalis and others offering diagnostics or MRD testing in cancer patients. This is a massive and well developed market. If Ultima can convince Natera to generate data on their platform instead of Illumina for some or all of their >3 Million tests per year, perhaps by exploring the instrument as Myriad appear to be doing, then the slight shift away from Illumina may become a landslide (with Core labs moving to e.g. Element)

I’ll finish up with a some questions for you? When will everyone start running combined genomics and proteomics as the default research liquid biopsy? Can blood proteomics supplant cfRNA-Seq? Is your imagination now the only sequence constraint – or is bioinformatics and interpretation going to remain the bottleneck for decades to come?

NB: I am not at all involved with AstraZeneca’s portion of the UK Biobank Pharma Proteomics Project.