Researchers at TU Graz’s Institute of Computational Biotechnology with scientists from the Austrian Centre of Industrial Biotechnology (acib), the Medical University of Graz and CNA Diagnostics GmbH (Grambach, Styria) have identified biomarkers that can be used to diagnose sepsis with high accuracy two to three days before the first clinical symptoms occur.
The test could significantly increase the chance of survival of sepsis patients and lower the negative side effects for sepsis survivors.
The research is published in two papers: “Evaluation of host-based molecular markers for the early detection of human sepsis”[1] and “Circulating cell-free DNA is predominantly composed of retro transposable elements and non-telomeric satellite
DNA”[2] in the Journal of Biotechnology.
Classification algorithms
“Our team has identified 24 biomarkers with which bacterial or fungal induced sepsis can be detected at an earlier stage when compared to the currently used tests, using newly developed classification algorithms,” explained Christoph W. Sensen, head of the Institute of Computational Biotechnology at TU Graz.
For their work, the bioinformaticians used sequencing data derived from anonymised plasma samples provided by the research groups led by Robert Krause, co-director of BioTechMed-Graz, and Peter Neumeister at the Medical University of Graz. The samples came from persons diagnosed with sepsis caused by bacteria or fungi, respectively, (in whose blood these pathogens were detected), influenza or lymphoma, as well as from healthy individuals. The sequencing data formed the basis for the development of the algorithms that were used to identify the markers, thus creating an unprecedented set of markers.
“This data set can be used to distinguish people in the early stages of sepsis and those with early clinical signs from healthy people and from people with other diseases,” said Sensen. “Within the patient group for which the markers were developed, the diagnostic accuracy was almost 90% in the period from two days before the first clinical signs until two days after diagnosis with the currently used diagnostic methods. In blind studies with patient groups that were not included in the marker development, the accuracy was still up to 81%.”
With the help of this method, sepsis can therefore be diagnosed much earlier than with any other diagnostic method.
In the course of their studies, the researchers also developed a new form of quantitative real-time PCR (Polymerase Chain Reaction) test. These kind of tests are often used to amplify the DNA or RNA of an infectious agent in a blood, plasma or serum sample, allowing the direct detection of bacteria or fungi in sepsis patients. In view of the large number of possible pathogen species which might cause sepsis, this is only possible to a very limited extent for sepsis patients and is therefore very imprecise.
The newly developed test of the Graz group, on the other hand, focuses on the body’s own signals, which are representative for the onset of sepsis for all bacterial and fungal cases. These can therefore be measured with much higher accuracy and also 2-3 days earlier than the direct detection of pathogens would allow.
Data from China shows that even Covid-19 patients with severe end-stage disease often had sepsis as a secondary disease. Sensen and his team are all the more interested in cooperating with biobanks such as BBMRI-ERIC and hospitals that are able to provide the team in Graz with plasma samples from Covid-19 patients. Because, according to Sensen: “On the basis of the sepsis early detection research programme, we should be able to develop diagnostic tools for the faster identification of high-risk patients and a strategy for early intervention at the first signs of sepsis, which can be used in future pandemics to reduce the consequences of the infection for those affected.”
References
[1] E. Ullrich, et. al. Evaluation of host-based molecular markers for the early detection of human sepsis. Journal of Biotechnology.
doi: https://doi.org/10.1016/j.jbiotec.2020.01.013
[2] S. Grabuschnig, et. al. Circulating cell-free DNA is predominantly composed
of retro transposable elements and non-telomeric satellite DNA. Journal of Biotechnology. 2020. doi: https://doi.org/10.1016/j.jbiotec.2020.03.002
