NEW YORK – New research is providing insights into the origins of proteins found in blood plasma, including disease-related ones, by tallying proteins and RNA in different cell or tissue types.
For a paper published in Cell on Wednesday, researchers at Lund University, the Roche Innovation Center Basel, and other institutions used mass spectrometry to profile proteins in eight blood cell types and 18 vascularized organ types, correlating them with proteins found in plasma samples.
After incorporating additional data from protein or RNA atlases spanning several cell or tissue types — including a cross-tissue expression atlas study that researchers from the European Molecular Biology Laboratory-European Bioinformatics Institute published in Nucleic Acids Research in 2021 and a quantitative proteome atlas outlined in a 2020 Cell study — the team put together a combined protein/RNA atlas spanning eight cell types and 21 tissues.
"The main goal of our study was to enable objective identification of tissue-derived proteins in plasma to enable monitoring of organ dysfunction in small amounts of blood plasma," co-senior and corresponding author Johan Malmström, a researcher affiliated with Lund University's clinical sciences department and the BioMS National Infrastructure in Biological and Medical Mass Spectrometry, said in an email.
To account for differences in findings from one cohort or analysis to the next, the team went on to establish a global label score (GLS) based on tissue- and organ-specific proteomic patterns found in each of the four atlases. This enabled them to highlight high-confidence protein patterns that scored relatively highly.
"Overall, we observe that the atlases show the same patterns in many cases but that there were also differences," Malmström said, noting that "[w]e believe that this highlights the importance of integrating information from several sources."
Together, the team's results revealed organ, tissue, or cell types that appeared particularly prone to have their proteins enriched in plasma, while identifying proteins that seemed to show consistent patterns across different atlases.
By bringing in blood proteomic profiles from the UK Biobank and from a preprint study of sepsis appearing in MedRxiv in 2024, the investigators were able to highlight changes in the levels of certain proteins in the blood in relation to conditions such as sepsis.
These plasma-enriched proteins "provide new opportunities to monitor organ dysfunction directly from a blood plasma sample," Malmström explained. "This is particularly relevant for diseases where organ dysfunction is a hallmark such as, for example, sepsis."
Building on their work, members of the team are planning to continue teasing out blood plasma protein changes that reflect tissue changes or disease, including protein features in thousands of blood samples from individuals suffering from sepsis.
"We aim to measure how panels of tissue-specific proteins change in concentration in the blood to rapidly quantify the level of organ dysfunction from a simple blood sample," Malmström noted. "Such information is intended to improve the prediction of disease progression and to find treatment-indicative biomarkers for sepsis."