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Plasma epigenomics: A new liquid biopsy paradigm

Project description

Plasma epigenomics as an extension of liquid biopsy technologies

Genomic DNA carries a multitude of post-translational modifications that reflect cells’ transcriptional states. Upon cell death, fragmented chromatin retaining histone modifications is released into circulation. The EU-funded cfChIP project aims to obtain plasma epigenomic information and translate it into medically relevant findings via liquid biopsy and chromatin immunoprecipitation of cell-free nucleosomes with chromatin marks followed by sequencing (cfChIP-seq). The previous study showed that cfChIP-seq provides multidimensional epigenetic information about the identity and the transcriptional state of the originating cells. The project will explore plasma samples from patients and donors in combination with probabilistic modelling to find correlations between tissue gene expressions and circulating chromatin profiles and how the immune system changes with disease progression and response to treatments.

Objective

Genomic DNA is packaged by histone proteins that carry a multitude of post-translational modifications, which reflect cellular transcriptional states. When cells die, fragmented chromatin retaining histone modifications is released to the circulation. Recently, we pioneered chromatin immunoprecipitation of cell-free nucleosomes carrying active chromatin marks followed by sequencing (cfChIP-seq). Our results show that cfChIP-seq provides multidimensional epigenetic information and that the plasma epigenome contains rich information about the identity and the transcriptional state of the originating cells.

Liquid biopsies already entered the clinical practice, yet current methodologies use them to assess genetic information. Our breakthrough methodology opens an unprecedented opportunity to delineate the transcriptional state of specific cell types and different pathologic states. Here we aim to translate plasma epigenomic information into medically relevant findings. The challenge is recovering the states of the cells represented in the circulation and relate these to pathological processes. Our working hypothesis is that this task is attainable by probabilistic modeling exploiting knowledge about epigenomics and transcription programs in health and disease. In this project we will assay plasma samples from multiple patient and donor cohorts to characterize the relation between tissue gene expression and circulating chromatin profiles, to recover the immune system status and chart how it changes with disease progression and response to treatment, and to monitor transplant patients for early detection of rejection.

Our extensive preliminary data, our expertise in probabilistic modeling and genomics and our collaborators’ access to relevant patient cohorts support the projects’ feasibility. Plasma epigenomics will open a new non-invasive window into tissue dynamics in living humans, beyond current liquid biopsy technologies, with far-reaching medical implications.

Host institution

THE HEBREW UNIVERSITY OF JERUSALEM
Net EU contribution
€ 2 962 500,00
Address
EDMOND J SAFRA CAMPUS GIVAT RAM
91904 Jerusalem
Israel

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Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 2 962 500,00

Beneficiaries (1)