New technology to get “protein fingerprints” in minutes

Researchers at Charité – Universitätsmedizin Berlin and the Francis Crick Institute have developed a mass spectrometric technique that can measure samples containing thousands of proteins within a few minutes. It’s faster and cheaper than a regular blood count.

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

Thousands of proteins are active in the human body at all times, providing structure and enabling vital reactions. The body increases and decreases the activity of certain proteins as needed, even when responding to external factors such as pathogens and drugs. The detailed patterns of proteins in cells, tissues and blood samples can therefore help researchers better understand diseases or make diagnoses and prognoses.

To get this “protein fingerprint”, researchers use mass spectrometry, a technology known to be both time-consuming and costly. ‘Scanning SWATH’, a new mass spectrometric technology, promises to change that. This technology, which was developed under the direction of Prof. Dr. Markus Ralser, Director of the Charité Institute for Biochemistry, and is much faster and cheaper than previous methods, enables researchers to measure several hundred samples per day.

“To speed up this technology, we changed the electric fields of the mass spectrometer. The data generated are so complex that humans can no longer analyze them,” explains Einstein professor Prof. Ralser, who is also a group leader at the Francis Crick Institute in London. He adds: “We have therefore developed computer algorithms based on neural networks and using this data to extract the relevant biological information. This enables us to identify thousands of proteins in parallel and to shorten the measurement timescales considerably. Fortunately, this one is Method also more precise. “

This high-throughput technology offers a wide range of applications, ranging from basic research to large-scale drug development to the identification of biological markers (biomarkers) with which the risk of an individual patient can be assessed. The technology’s suitability for the latter was demonstrated by the researchers’ study on COVID-19. As part of this research, the team analyzed blood plasma samples from 30 inpatient Charité patients with COVID-19 of varying severity and compared the protein patterns obtained with those of 15 healthy people. The actual measurements on individual samples only took 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 been linked to disease severity in previous studies, no such relationship was established for 11 of the proteins identified. Some 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 a very short time, we discovered protein fingerprints in blood samples, with which we can now categorize 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 their illness. However, in order to use mass spectrometry analysis for routine categorization of COVID-19 patients, this technology needs to be further refined and turned into a diagnostic test. It may also be possible to use rapid protein pattern analysis to predict the likely course of a COVID-19 case. While the initial results we have gathered are promising, more study is needed before these can be applied in routine practice. “

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

Prof. Ralser is convinced that mass spectrometric examinations of the blood could one day supplement conventional blood count profiles. “Proteome analysis is now cheaper than a complete blood count. By identifying many thousands of proteins at the same time, proteome analysis also provides a lot more information. I therefore see enormous potential for broad application, for example in the early detection of diseases. We will therefore become ours Studies continue to be used to develop proteome technology for this type of application. “

Source:

Charité – University Medicine Berlin

Journal reference:

Messner, CB et al. (2021) Ultrafast Proteomics with Scanning SWATH. Natural biotechnology. doi.org/10.1038/s41587-021-00860-4.

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