New technology to get “ protein fingerprints ” in minutes

Researchers from Charité – Universitätsmedizin Berlin and the Francis Crick Institute have developed a technique based on mass spectrometry capable of measuring samples containing thousands of proteins in just a few minutes. It is faster and cheaper than a conventional blood count.

To demonstrate the potential of the technique, the researchers used blood plasma collected from patients with COVID-19. Using the new technology, they identified eleven previously unknown proteins that are markers of disease severity. The work was published in Biotechnology of nature.

Thousands of proteins are active inside the human body at all times, providing its structure and enabling reactions essential to life. The body increases and lowers the activity levels of specific proteins as needed, including when it responds to external factors such as pathogens and drugs. Detailed diagrams of proteins found in cells, tissues and blood samples can therefore help researchers better understand diseases or make diagnoses and prognoses. In order to obtain this “protein footprint”, the researchers use mass spectrometry, a technology known to be both time consuming and expensive. “SWATH Scanning”, a new technology based on mass spectrometry, promises to change that. Developed under the direction of Professor Markus Ralser, director of the Institute of Biochemistry of Charité, this technology, much faster and cost-effective than previous methods, allows researchers to measure several hundred samples per day.

“In order to accelerate this technology, we have modified the electric fields of the mass spectrometer. The data produced is so extremely complex that humans can no longer analyze it, ”says Professor Einstein, Professor Ralser, who is also a group leader at the Francis Crick Institute in London. He adds: “So we have developed computer algorithms based on neural networks that use this data to extract relevant biological information. This allows us to identify thousands of proteins in parallel and dramatically reduces the measurement time scales. Fortunately, this method is also more precise. “

This high-throughput technology has a wide range of potential applications, from basic research and large-scale drug development to the identification of biological markers (biomarkers), which can be used to estimate a patient’s risk. individual. The suitability of the technology for the latter has been demonstrated by the researchers’ study of COVID-19. As part of this research, the team analyzed blood plasma samples from 30 hospitalized Charité patients with COVID-19 of varying degrees of disease severity, comparing the protein profiles obtained with those of 15 people. in good health. Actual measurements made on individual samples took only a few minutes.

The researchers were able to identify a total of 54 proteins whose serum levels varied depending on the severity of COVID-19. While 43 of these proteins had already been linked to disease severity in previous studies, no such relationship had been established for 11 of the identified proteins. Several of the previously unknown proteins associated with COVID-19 are involved in the body’s immune response to pathogens, which increases the tendency to clot.

In the shortest possible time, we discovered protein fingerprints in blood samples that we are now able to use to categorize COVID-19 patients based on disease severity. This type of objective assessment can be extremely valuable, as patients sometimes underestimate the severity of their illness. However, in order to be able to use mass spectrometry analysis for routine categorization of COVID-19 patients, this technology will need to be further refined and turned into a diagnostic test. It may also become possible to use rapid analysis of protein patterns to predict the likely course of a case of COVID-19. While the initial results we have gathered are promising, more studies will be needed before this can be used in routine practice. “

Dr Christoph Messner, lead author of the study, researcher at the Institute of Biochemistry of Charity and the Francis Crick Institute

Professor Ralser is convinced that blood tests based on mass spectrometry could one day supplement conventional blood count profiles. “Proteomics analysis is now cheaper than a complete blood count. By identifying several thousand proteins at the same time, proteomics analysis also yields a lot more information. So I see enormous potential for widespread use, for example. example in the early detection of diseases. We will therefore continue to use our studies to develop proteome technology for this type of application. “