Publication highlights March 2025
The power of NGS-based proteomics
In this month’s Olink publications blog, we take a look at some recent examples of how NGS-based proteomics using the Olink® Explore platform is enabling impactful discoveries across the breadth of biomedical research. Using NGS to quantify protein data from Olink’s Proximity Extension Assay (PEA) technology has opened up new possibilities for accurate, specific measurement of thousands of proteins at any scale of study.
You may also be interested to learn about the newly launched Olink Reveal, which provides accessible NGS-based proteomics for every lab.
A proteomic signature of HIV-associated cardiovascular changes.
People living with HIV are at higher risk of heart failure and associated left atrial remodeling (LAR) compared to people without HIV. Mechanisms are unclear but have been linked to inflammation and premature aging. A team from John Hopkins University combined plasma proteomics using Olink Explore 3072 with cardiac magnetic resonance imaging (CMRI) data to identify parallels between HIV-related and aging-related immune dysfunction that could contribute to LAR and clinical heart failure (HF).
They identified a protein signature that may reflect or contribute to HIV-associated LAR many features of which were associated with older age and time to incident HF. The proteins involved suggested that there may be pathways shared in HIV and aging that may contribute to the risk of heart failure.
If successfully validated in other external populations, these proteins may help refine current risk prediction models and help identify therapeutic targets for heart failure among both people with and without HIV.
Cardiometabolic proteins with causal involvement in fragility fractures.
Cardiovascular diseases (CVD) predispose individuals to a higher risk of fragility fractures, but the mechanisms are not well understood. A group from Uppsala University used multiple Olink Target 96 panels to identify proteins associated with increased risk of fragility-related fractures in two elderly population-based cohorts. Mendelian Randomization (MR) analysis using proteogenomic data generated using Olink Explore 3072 in the UK Biobank Pharma Proteomics Project was then performed to examine whether the proteins identified could play causal roles in CVD-associated frailty fractures. This provided robust evidence that four proteins are all causally linked to increased risk of fragility fractures.
These data reveal biological links between cardiovascular diseases and fragility fractures. The proteins should be further evaluated as shared targets for developing pharmacological interventions to prevent fractures and cardiovascular disease.
Predictive biomarkers of kidney function in type 2 diabetes
The rate of kidney function decline, as monitored by estimated glomerular filtration rate (eGFR), varies among patients with type 2 diabetes (T2D). A team from Teck Puat Hospital in Singapore used the Olink Explore 1536 platform to identify plasma proteins associated with different eGFR trajectories in T2D patients. Based on eGFR measurements, subjects were divided into groups with slow, progressive or accelerated decline, with the accelerated decline group showing the greatest risk of adverse renal outcome.
19 proteins associated with accelerated eGFR decline across the three groups were identified and multivariable logistic regression was used to develop protein signatures that significantly improved a risk score based on current clinical risk factors.
Integrating proteomic biomarkers with traditional risk factors significantly improves the ability to identify high-risk patients.
The roles of genetics and environment in aging and mortality
Recent studies indicate that the genome may have a relatively modest effect on lifespan. This is corroborated by the observation that average human lifespan has doubled in just 200 years, suggesting that nongenetic environmental factors play a key role in aging and premature mortality. A study from the University of Oxford has looked at biological aging, chronic diseases, and mortality in relation to environmental and lifestyle factors (the “exposome”) in almost half a million subjects in the UK Biobank (UKB). Exposome and genome associations with aging were analyzed in relation to a proteomic age clock derived from measurements of ~3,000 proteins in over 45,000 individuals using Olink Explore 3072 in the 1st phase of the UKB Pharma Proteomics Project.
Their remarkable findings around the contributions of environment and genetics to mortality and incidence of common age-related diseases suggest that the exposome shapes distinct patterns of disease and mortality risk, irrespective of polygenic disease risk factors.
Overall, our results indicate that environment-focused interventions are possibly the most strategic starting point for ameliorating premature mortality and most age-related morbidity.
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