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UK Biobank’s Plasma Protein Study Places Proteomics at the Forefront of Multiomic Disease Research

By Olink

The UK Biobank’s recent decision to add proteome information to its genetic database exemplifies a recent trend to use big data and a multiomics approach to better understand drugs and disease.

The collaborative project, funded by several large biopharmaceutical companies, has tapped Olink Proteomics to measure the concentrations of around 1,500 plasma proteins in more than 50,000 UK Biobank participants.

While genomics, transcriptomics, and proteomics profiling are not new techniques, new technological advances are changing how the industry is using them together to gain a more complete picture of diseases of interest.

According to Olink, the project demonstrates the unique value of proteomics within multiomics projects. “It is at the protein level where things get really interesting, as it illustrates human biology as it happens, when it happens,” said Evan Mills, the director of Strategic Accounts at Olink. “The ability to measure human biology in real time is the key to making progress in disease and therapeutics.”

Proteins are the true indicators of the interaction between genes and environment, said Mills. “Recent advances in the throughput and reliability of proteomics tools indicate that a proteomics revolution is underway,” he added.

Barriers to uptake and enabling technology

The greatest challenge to the proteomics field thus far has been the lack of tools that could adequately obtain the level of information garnered using other -omics approaches. Past technology was low throughput, expensive, and slow; or it could not provide highly multiplexed proteomics data with the quality standards that are required to complement genomics and transcriptomic data.

The UK Biobank plasma proteome project is looking to prove that proteomics tools have improved enough to overcome these limitations.

In June of 2020, Olink released a version of its multiplex immunoassay platform, Olink Explore 1536, which runs on the Illumina NovaSeq next-generation sequencing (NGS) platform – the same system that the UK Biobank has been using for whole-exome sequencing.

Olink technology employs matched pairs of DNA-coupled antibodies that generate a small DNA amplicon upon binding to the correct protein (see figure below). Readout of this signal was previously achieved using qPCR, but with Olink Explore, the readout is on NGS. This upgrade has vastly improved the throughput and breadth of protein coverage. With NGS, Explore 1536 can measure 1,500 proteins using less than 3 microliters of blood with a throughput that was unprecedented just a year ago.

This approach will allow a wide range of large population cohort studies to add proteomics to their genomic and transcriptomic data sets. Starting in 2021, the UK Biobank project will analyze 56,000 samples in the space of four to five months using Olink’s proteomics immunoassay platform.

Efficiency in drug discovery

There are numerous potential benefits of harnessing proteomics profiling in drug discovery, which is widely known to be an inefficient and at times frustrating enterprise. By combining proteomics with genomics data, biopharmaceutical companies will be able to understand which potential therapeutic protein targets are linked to genetics. And several studies have demonstrated that therapeutic programs with genetic as well as protein evidence have a twofold increase in chances of success in the clinic.

Many therapeutic studies fail because they are not targeting the right proteins. Using proteomics technologies, researchers can determine early on whether a potential protein target will be worthwhile pursuing, saving pharma companies money while also ultimately helping patients and the healthcare systems supporting them.

Future developments

Mills said that Olink considers the Explore 1536 to be the first step in bringing “the proteomics revolution” to fruition. Within the next year, the company plans to double the number of proteins available for analysis on the platform and, in the next two years, triple it.

It’s possible, he surmised, that with that much analytical power, “proteomics may indeed become the field that drives human health and disease biology into the future.”

Find out more about the Olink Explore 1536 here.

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