Whether it activates or silences genes, breaks down damaged cells, or builds new tissue, our body is constantly working to repair itself. To fight the disease, our body sends signals, often long before we even notice the disease. Such signals are, for example, DNA molecules that are released from the body’s cells, circulate in the blood, and other cells most likely recognize them as a message to trigger a defensive response.
Researchers at the TU Graz Institute of Computer Biotechnology have identified these messengers and developed a revolutionary method. Using endogenous signals (i.e., biomarkers), sepsis can be diagnosed with great accuracy two to three days before the onset of the first symptoms. A test based on this method could significantly increase the chance of survival of patients with sepsis. Researchers have now published details on this in two papers, “Evaluation of Host-Based Molecular Markers for Early Detection of Sepsis in Humans” and “Circulating DNA without Cells is Mainly Composed of Retrotranslable Elements and Non-telomeric Satellite DNA” in the Journal of Biotechnology (Elsevier).
Classification algorithms serve as a basis
“Our team has identified 24 biomarkers that can detect bacterial or fungal sepsis at an earlier stage compared to currently used tests, using a classification of newly developed algorithms,” explains Christoph W. Sensen, head of the Institute of Computer Biotechnology at TU Graz.
Bioinformatics used sequencing data obtained from anonymous plasma samples. The samples come from people diagnosed with sepsis, caused by bacteria or fungi (in whose blood these pathogens have been identified), influenza (a disease with symptoms partly similar to sepsis) or lymphoma, as well as from healthy individuals.
Sequencing data formed the basis for the development of the algorithms used to identify markers, thus creating an unprecedented set of markers. “This data set can be used to distinguish people in the early stages of sepsis from healthy people. In the group of patients for whom markers were developed, diagnostic accuracy was almost 90 percent in the period from two days before the first clinical signs to two days after diagnosis using the currently used diagnostic methods. In studies with random groups of patients, which were not involved in the development of markers, the accuracy was still up to 81%. ”
Clinical research and FDA approval on the go
During their research, the researchers also developed a new form of quantitative real-time PCR test. PCR is a polymerase chain reaction, a method of amplifying (highlighting) nucleic acids. PCR-based tests are already used in clinics, for example to detect SARS-CoV-2 virus in patients.
These types of tests are often used to amplify DNA agents from a blood sample to detect the cause of sepsis. However, given the large number of possible pathogens that can cause sepsis, this is possible to a very limited extent in patients with sepsis and is therefore very imprecise.On the other hand, the newly developed test focuses on the body’s own signals, which are representative of sepsis caused by all bacteria and fungi.
These signals can therefore be measured with much greater accuracy, and also 2-3 days earlier than direct detection of pathogens would allow. Approval from the U.S. Food and Drug Administration (FDA) in Washington has already been requested and a clinical trial has begun. Work on the approval in Europe is just beginning. Christoph W. Sensen hopes the tests will be used extensively soon.”However, the pandemic caused by SARS-CoV-2 is slowing us down a bit, because American hospitals will not be able to deliver plasma samples for some time due to the current situation.”
Further plasma samples are required
The data show that even more severe patients with COVID-19 often developed sepsis. Sensen and his team are looking for biobanks, such as BBMRI-ERIC, that can provide his team with plasma samples from patients infected with SARS-CoV-2.