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

Introduction

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.

Limitations of Current Strategies

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

Underexplored Field

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 to state-of-the-art methods because it offers targeted and multiplexed amplifications of exclusively informative genomic regions (i.e., promoters and enhancers).

Advantages of Histone PTM Strategies

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

Challenges in Development

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.

Proposal Overview

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

Research Plan

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.
2. Develop a market strategy and navigate product development opportunities for commercialization of the method.

Conclusion

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.