Novel Diagnostics through Methylation Profiling of Cell-free DNA

Cell-free DNA (cfDNA) is increasingly being used to detect and
characterize diseases. Recently, methodological advances to
analyse cfDNA methylation, and the detection of cfDNA in bodily
fluids beyond plasma, have expanded the spectrum of clinical
conditions where cfDNA is applicable.
In a pilot study, we demonstrated that cfDNA methylation can be
used to presymptomatically predict preeclampsia, a prevalent cause
for peripartal mortality and morbidity. This is a potential gamechanger
in prenatal care, as accurate early prediction enables
effective prophylactic treatment. We here propose 1.) to expand this
study from monocentric to multicentric, in order to build better
prediction models, 2.) to apply the optimized model for the
development a highly targeted cfDNA methylation panel, and 3.) to
demonstrate the performance of this classifier in an independent
patient cohort. Finally, we want to identify the sources of these DNA
methylation changes by analysing tissues that potentially contribute
to preeclampsia.
Additionally, building on this successful pilot, we propose 2 novel,
independent studies. Specifically, we will apply cfDNA methylome
analysis to aqueous and vitreous humour samples, in order to
diagnose uveal melanomas, and to urine samples, in order to
diagnose IgA nephropathy. Similar to preeclampsia, both diseases
are in dire need of better and more accessible diagnostic and
predictive handles.