New technology to find ‘protein fingerprints’ in minutes

Researchers from Charité – Universitätsmedizin Berlin and the Francis Crick Institute have developed a large-scale spectrametry-based device capable of measuring samples containing thousands of proteins within a few minutes. It is faster and cheaper than a normal blood count.

To demonstrate the potential of the technology, the researchers used blood plasma collected from COVID-19 patients. Using the new technology, they identified eleven previously unknown proteins that are indicators of the severity of disease. The work was published in Nature’s biotechnology.

There are thousands of active proteins inside the human body at any given time, providing its structure and enabling life-essential reactions. The body increases and decreases activity levels of certain proteins as needed, including when responding to external factors such as pathogens and drugs. Thus the precise patterns of the proteins found inside cells, nappies and blood samples can help researchers to better understand diseases or to make studies and prognoses. To obtain these ‘protein fingerprints’, researchers use mass spectrametry, a technology known to be both time-consuming and cost-intensive. ‘Scanning SWATH’, a new technology based on mass spectrametry, promises to change this. Developed under the direction of Prof. Dr. Markus Ralser, Director of the Charité Biochemistry Institute, says this technology, which is much faster and more cost-effective than previous methods, allows researchers to measure several hundred samples per day.

“To accelerate this technology, we modified the electric fields of the cosmetic spectrometer. The extracted data are so complex that people cannot analyze them,” explained Dr. Einstein Professor Ralser, who is also the Francis Group Director. Crick Institute in London. He said: “We have developed cloud-based computer algorithms that use this data to extract the relevant biological information. This allows us to identify thousands of proteins simultaneously and to greatly reduces measurement timescales. Fortunately, this method is also more accurate. “

This high-throughput technology has a wide range of potential applications, from basic and large-scale drug development and development to the identification of biological markers (biomarkers), which can be used to estimate individual patient risk. The suitability of the technology for the latter was revealed by the researchers ’study of COVID-19. As part of this research, the team analyzed blood plasma samples from 30 patients within Charité with COVID-19 of varying degrees of disease severity, comparing the protein patterns obtained with those of 15 individuals. healthy. The actual measurements taken on individual samples took only a few minutes.

The researchers were able to identify a total of 54 proteins whose serum levels varied according to the severity of COVID-19. Although 43 of these proteins had been linked to disease depth during earlier studies, no such relationship was established for 11 of the identified proteins. Several previously unrecognized COVID-19-associated proteins are involved in the body’s immune response to pathogens that increase clotting predisposition.

In the shortest time, we found protein fingerprints in blood samples that we are now able to use to classify COVID-19 patients according to the severity of the disease. This type of objective assessment can be extremely valuable, as patients sometimes underestimate the severity of the disease. However, in order to be able to use large spectrometry analysis for routine classification of COVID-19 patients, this technology needs to be further redefined and turned to diagnostic testing. It may also be possible to use protein pattern analysis to predict a course similar to that of COVID-19. While the initial results we collected are promising, further studies will be needed before this can be used in routine practice. “

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

Professor Ralser is convinced that large-scale spectrametry-based blood tests on the blood could contribute to routine blood counts. “Proteomeome analysis is now cheaper than whole blood count. By identifying thousands of proteins at once, proteomic analysis also reveals a lot more information. So I sees great potential for its widespread use, for example in the early detection of diseases, so we will continue to use our studies to develop proteome technology for this type of application. “