Deep multiplexed epigenetic profiling of plasma cell-free nucleosomes for early cancer diagnostics

Over recent years, cancer diagnostics based on cell-free DNA (cfDNA) in liquid biopsies demonstrated great promise in guiding treatment and screening for recurrent diseases.

Current diagnostic strategies are mainly based on the analyses of DNA mutations, fragment length or DNA methylation status.

However, these strategies do not provide a universal approach for cancer identification, are costly and labour intensive, and generally fall short in detecting cancer at early tumorigenic stages or minimal residual disease.

An underexplored field, is the development of diagnostic applications based on histone post-translational modifications (PTMs).

The strategy to harness these epigenetic signatures to identify cell-of-origin is potentially superior over state-of-the art methods because it offers targeted and multiplexed amplifications of exclusively informative genomic regions (i.e. promoters and enhancers).

Such strategies are cost-effective and display much increased sensitivity over existing methods in their accuracy in e.g. early cancer diagnoses, relapse detection or screenings.

Unfortunately, the development of this field is hampered by a lack of methods that are sensitive enough to detect multilayered histone PTM-signatures in samples with limited material such as blood plasma.

This proposal describes our plan to implement two new strategies, for ultra-sensitive detection of multi-layered histone PTMs signatures in blood plasma.

Our proposal outlines 1) a research plan for the implementation and optimization of these strategies to profile histone PTM profiles in plasma of healthy and patient material to determine the diagnostic potential of the method and 2) develop a market strategy and navigate product development opportunities for commercialization of the method.

Successful execution of this proposal will result in the establishment of a novel diagnostic strategy with unprecedented potential for universal cancer screening-approaches based on liquid biopsies.