Bruker Corporation (Nasdaq: BRKR) announced a seminal bioRxiv preprint describing a draft atlas of the human plasma proteome. The atlas maps proteins at isoform, or proteoform, resolution. Researchers conducted the study under principal investigator Markus Ralser at Charité – Universitätsmedizin Berlin. The team also included several collaborators.
The preprint, “A draft atlas of the human plasma proteome at isoform resolution,” appeared on September 28, 2026. Researchers published the work through bioRxiv. The study combines intact protein fractionation with diaPASEF mass spectrometry. The researchers performed the analysis on Bruker timsTOF mass spectrometry systems.
With this approach we identified 5,077 plasma protein groups. It also identified 179,049 unique proteoforms in the plasma samples analyzed. A high-confidence map contained 44,083 proteoforms. They found a median of eleven proteoforms per protein.
These results demonstrate the enormous complexity of the human plasma proteome. Traditional protein lists capture only part of this molecular diversity. Furthermore, canonical proteins may represent less than half of the total protein content in serum.
“Human plasma contains far more molecular diversity than conventional protein lists suggest,” said Dr. Markus Ralser, Einstein Professor of Biochemistry and Head of the Institute of Biochemistry at Charité – Universitätsmedizin Berlin. “This first draft of the plasma proteoform atlas shows that proteoforms are not rare exceptions, but a defining feature of plasma biology. Mapping this diversity opens an enormous, largely unexplored molecular space for understanding physiology, disease mechanisms and differentiated biomarkers.”
Plasma Proteomics Reveals Extensive Proteoform Diversity
The atlas demonstrates substantial proteoform diversity among abundant plasma proteins. These proteins support several important biological functions. They include molecular transport, complement activity, and coagulation. Furthermore, the study provides a framework for understanding differences between protein measurement technologies. These differences can become particularly important for low-abundance proteins. They also matter for proteins that occur across numerous molecular isoforms.
The researchers did not use nanoparticle-based enrichment during the workflow. Instead, they combined intact-protein fractionation with sensitive, high-throughput mass spectrometry. This strategy allowed the team to resolve plasma proteoform diversity at an unprecedented scale. The findings could therefore expand research into plasma biology and biomarker discovery. Researchers can use the atlas as a foundation for future proteomics investigations. It may also support more detailed studies of protein isoforms and their biological roles.
Mass Spectrometry Supports Precision Medicine Research
“This landmark discovery moves plasma proteomics beyond counting protein groups toward resolving the molecular isoforms that actually carry biological and ultimately biomedical function,” said Dr. Daniel Hornburg, Bruker Vice President, Biomarkers & Precision Medicine. “The combination of protein separation, diaPASEF and sensitive timsTOF mass spectrometry provides a powerful foundation for studying proteoform-specific biology and for developing the next generation of more specific drug targets and biomarkers.”
The draft isoform atlas will be a launching pad for more detailed research on proteoforms. Future studies could compare these proteoforms among individuals. Researchers can also look at differences between physiological states and disease. The work could help scientists gain a better understanding of how molecular differences influence biological processes. It may also help to identify more specific biomarkers of disease. In addition, the findings can be used by researchers to find possible therapeutic targets.
“Resolving protein isoforms and their modifications is fundamental to understanding the molecular drivers of disease,” said Dr. Rohan A. Thakur, Bruker Daltonics EVP and President of TofWerk. “The breakthrough timsOmni platform now enables deep top-down sequencing with near-complete sequence coverage on many proteoforms, combined with PTM localization and quantitation for in-depth functional proteome studies.”
This study adds to the knowledge of protein diversity in human plasma. The combination of intact protein fractionation, diaPASEF and timsTOF mass spectrometry provides a detailed analytical workflow. The resulting atlas provides researchers with a wider view of plasma proteomics. It also provides opportunities for the future studies on disease mechanisms and biomarker development. As proteomics research progresses, proteoform-level measurements might provide more biological information than the traditional protein-group measurements.
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News Source: Businesswire.com
