Researchers at Fudan University in Shanghai, China, have created an atlas of the human plasma proteome based on data from over 53,000 adults. This data can enable precision medicine by helping researchers understand which proteins are linked to diseases and which are health-related.
The study was recently published in the journal Cell. Using data from the UK Biobank, the researchers associated 2,920 plasma proteins with 406 prevalent diseases, 660 incident diseases, and 986 health-related traits. Examples of studied diseases were gastrointestinal, musculoskeletal, genitourinary, circulatory, respiratory, and infectious diseases, while health-related traits included mental health, cognitive function, diet, lifestyle, working and living environment, and medical history.
Using this data, the team was able to map a comprehensive proteomics atlas for 1,706 human diseases and traits. This allowed them to identify promising predictive and diagnostic biomarkers for different diseases, as well as 26 potential therapeutic targets with good safety profiles and 37 drugs that could potentially be repurposed.
Several other studies allowed the researchers to confirm the validity of their approach, for example, certain cancer biomarkers can be associated with COVID-19 severity, and the biomarker growth differentiation factor (GDF)15 plays a role in different mechanisms, including inflammation, stress signaling, tissue repair, and tumorigenesis.
However, the team also discovered new protein-disease and protein-health relationships that had not yet been reported: The main associations were found in the incidence of genitourinary diseases, such as chronic kidney disease, where the researchers discovered new biomarkers with high-hazard ratios, including NBL1 and COLEC12.
In their atlas of the human plasma proteome, the researchers also mapped almost 2,000 protein associations that had protective mechanisms against prevalent and incident diseases.
“Among these proteins, EGFR exhibited the most extensive and significant protective effects, impacting 90 diseases,” the researchers wrote in their paper. “The largest protective effect was on hypertensive renal disease […], supporting the pivotal role of EGFR signaling in kidney damage.”
Other studies have also looked into the relationship between plasma proteins and diseases. A recent study by researchers at the University of Oxford, for example, discovered that analyzing the plasma proteins of sepsis patients can provide insights into the severity and prognosis of the disease.
Furthermore, in 2021, researchers at Washington University School of Medicine developed an atlas of the brain proteome, which allowed them to identify potential drug targets for the treatment of Alzheimer’s and Parkinson’s disease, amyotrophic lateral sclerosis (ALS), and stroke.
In this most recent study of the human plasma proteome, the researchers found that at least 50 diseases shared more than 650 proteins, and over 1,000 proteins revealed sex and age heterogeneity. The average age of participants was 56.8 years and the participant population comprised 53.9% women and 93.7% white people. This lack of diversity reveals a limitation within the study, which was also acknowledged by the researchers:
“[…] the individuals included in this study were predominantly white Europeans. The insufficient sample size of other ancestries in the [UK Biobank] limits the power of extending the current discoveries to the whole population, emphasizing the necessity of further proteomic studies in large-scale non-European ancestral cohorts.”
This open-access atlas of the human plasma proteome nevertheless provides new insights into the biological mechanisms of different diseases, supporting researchers in understanding and assessing disease biomarkers and finding potential therapeutic targets.
