Unlocking the Human Proteome

The UKB-PPP aims to create a comprehensive map of proteins in the human body. The study will analyze more than 5,400 proteins from 600,000 patient samples, making it the most extensive study of the human proteome.  

Proteins are the molecules that carry out the biological functions necessary for life, so when proteins are broken or missing, it can often lead to conditions like cancer and neurodegenerative diseases. Scientists have been studying proteins and what they can tell us about our health for decades, but until now, methods for analyzing the entire set of our proteins (proteomics) have remained out of reach for many researchers.  

We expect that the findings from the study will fuel the discovery of new biomarkers to help identify new, more precise ways to treat diseases. 

The ambitious scale of the UKB-PPP presents numerous technological challenges. A primary obstacle is the large volume of samples that will need to be analyzed. This requires a solution that could scale in throughput while keeping resources, cost and hands-on time to a minimum. For example, some proteomics methods may scale well, but the hands-on time, number of consumables involved and/or overall cost can make them difficult to employ for a project of this size. 

Importantly, because of the high amount of data generated, the methods used for analysis must produce consistent, reliable data. This includes the ability to measure proteins of low abundance in samples that only a few proteins may dominate. Similar to trying to take good photos in a scene with both bright light and dark shadows, solutions must have excellent dynamic range. These specific challenges influenced how the technologies were selected. 

After a rigorous review process conducted by some of the world’s leading pharmaceutical researchers, the Olink Explore HT Platform from Thermo Fisher Scientific was chosen because it best overcomes the challenges presented by the UKB-PPP project. 

Because of the comprehensive nature of this data, which reflects protein levels over time in the human body, analyzing samples efficiently is critical for a project of this size. The Olink Explore HT platform will enable the UKB-PPP to analyze thousands of samples and generate tens of millions of data points per week. Once fully implemented, the project is expected to analyze over 9,000 samples per week using only one dedicated scientist, maximizing throughput while minimizing cost, waste and hands-on time that could lead to additional errors. 

Importantly, the data generated must be highly reliable. Olink Explore HT employs the innovated Proximity Extension Assay (PEA) technology that uses a dual-recognition, DNA-coupled technology to deliver industry-leading specificity, eliminating wrong targets that could lead to misinterpretation and wasted resources. Every assay undergoes a rigorous validation process and the protein selection strategy targets functional, actionable, druggable and circulating proteins identified from protein annotations, publications, clinical trials, approved therapies and researcher requests. This strategy allows researchers to gain deeper biological insights that can impact how we diagnose, monitor and treat disease. 

A few key considerations must be made to ensure the integrity and reproducibility of proteomic data across this large dataset. One consideration is that the data needs to be reliable and delivered at scale to help facilitate detailed protein analysis across large datasets. Another consideration is that the data should be well-characterized with complete detail and stored in a centralized location to allow standardized and uniform information to be used in various research applications.  

The robustness and consistency of PEA technology has been thoroughly analyzed in a concordance study comparing the same samples across all Olink products and readout platforms. Remarkably high correlations are seen for the same protein measured using different panels, from high-throughput proteomics with Olink Explore HT to cytokine analysis with Olink Target 48. In addition, over 2,500 peer-reviewed publications cite Olink’s PEA technology, providing rigorous validation and understanding of the underlying methods for Olink Explore HT. 

The UKB-PPP aims to support future drug discovery by creating a comprehensive map of the 5,400+ proteins in the human body. This map can help researchers identify new proteins that play a role in disease development and progression and find ways to target those proteins more precisely to treat diseases. Data from the UKB-PPP can help validate new drug targets, enhance diagnostics and accelerate targeted drug discovery, leading to safer and more effective medications. It may also help identify additional uses for existing treatments.  

The data from the UKB-PPP will be made available to UK Biobank-approved researchers worldwide as a shared resource to ensure future drug discoveries are based on the latest understanding of the proteome.  

The results of this study have the potential to fundamentally change how we diagnose and treat disease. In addition to supporting the discovery and development of novel therapies, we hope the data will help researchers better understand the effects of genetic differences, lifestyle and environmental factors on health. We could see the data being used to help identify new protein biomarkers that can help predict and diagnose a wide range of diseases and support the identification of new pathway associations with disease, leading to a deeper understanding of the commonalities among diverse diseases.  

Already we have seen the strong potential of the UKB-PPP. An earlier pilot study using proteomics data from 54,000 samples provided by UK Biobank identified protein risk factors for certain cancers up to seven years before diagnosis.