Study reveals molecular profiles of Parkinson's disease

The second most common neurodegenerative disorder in the world is Parkinson’s disease, but despite this fact, not much is known about the causes and progression of this medical condition.

Study reveals molecular profiles of Parkinson
Andreas Keller, the professorship for clinical bioinformatics at Saarland University and spokesman for the Center for Bioinformatics on the Saarland Informatics Campus. Image Credit: © Oliver Dietze.

To diagnose this neurodegenerative disorder at an early phase, make prognoses, and design new treatments, biomarkers are required that indicate its development and progression.

At Saarland University, bioinformaticians have looked for such biomarkers and targeted ribonucleic acids, or RNA. The research work was published in the Nature Aging journal.

The research team, headed by bioinformatics professor Andreas Keller and his doctoral student Fabian Kern, has demonstrated that it is possible to trace the course of Parkinson’s disease by using the concentration of non-coding RNAs in the blood of a patient suffering from this disorder.

For this analysis, the molecular profiles of over 5000 blood samples collected from more than 1600 Parkinson’s patients were generated and evaluated. This led to about 320 billion data points, which were investigated for biomarkers of Parkinson’s disease with the help of artificial intelligence techniques.

Our project is one of the most extensive RNA studies in the world,” stated Andreas Keller, head of the research team for clinical bioinformatics at Saarland University and is also the spokesman for the Center for Bioinformatics on the Saarland Informatics Campus.

The concentration of a unique class of RNAs, the so-called microRNAs, in the blood samples was specifically fascinating. MicroRNAs are essentially short, non-coding parts of RNA that play a crucial regulatory role in the translation of genetic data.

Since microRNAs are stable in the bloodstream, contain a wide range of information for diagnosis and prognosis, and their influence on the genes of an organism has been well researched, we consider them to be promising candidates for reliable biomarkers, also in the context of Parkinson’s disease.”

Fabian Kern, Study First Author, Saarland University

Kern is a doctoral student in Keller’s research team.

In other large-scale analyses, Keller’s research team has successfully identified microRNAs as diagnostic biomarkers for lung cancer and Alzheimer’s disease.

With regard to Parkinson’s disease, the bioinformaticians from Saarland University have now demonstrated that this disorder runs in specifically robust molecular waves in the third decade onwards and from the age of 70.

This is indicated by the increased concentration of deregulated microRNAs that we found in blood samples from the corresponding study cohorts.

Andreas Keller., Bioinformatics Professor, Saarland University

To make this evaluation, the investigators collected the blood samples from one of the biggest Parkinson’s research works in the world, called the “Parkinson’s Progression Markers Initiative (PPMI)” from the United States.

Since the PPMI dataset happens to be a longitudinal analysis, the researchers addressed the query of whether the microRNA concentration changes over the time axis, which could help reach a conclusion about the course of Parkinson’s disease.

In the new study, the bioinformaticians from Saarland University worked with whole blood samples and assessed the overall level of the microRNAs in all types of blood cells. The team was able to demonstrate that the data content of specific types of cells changes based on the stage and age of the disease in a patient.

In the future, we want to analyze the blood down to the single-cell level, which will enable us to make much more precise statements,” added Keller with a focus on upcoming research projects.

The new study involved a total of 11 institutions, including global leaders like the American elite Stanford University, in which Keller worked as a visiting professor back in 2019 and 2020; the Translational Genomics Research Institute (TGen) based in Phoenix; the University of Southern California situated in Los Angeles; and the University of California at San Diego.

We are of course very pleased that our expertise in the field of microRNAs and bioinformatics is also valued on an international level and that we play a leading role in a predominantly American study and is a quality criterion for research at the Saarland Informatics Campus.”

Andreas Keller., Bioinformatics Professor, Saarland University

Source:
Journal reference:

Kern, F., et al. (2021) Deep sequencing of sncRNAs reveals hallmarks and regulatory modules of the transcriptome during Parkinson's disease progression. Nature Aging. doi.org/10.1038/s43587-021-00042-6.

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