Detecting diseases from blood cell-free chromatin

Cells throughout our body constantly die and are replaced by new ones. When cells die, they leak short fragments of their DNA into the blood. These DNA fragments in the blood are bound to dedicated structural proteins called histones. Beyond their structural role, histones carry rich epigenetic information in the form of chemical marks that together compose an elaborate epigenetic code. This code closely relates  and can report on the gene expression activity in the cells from which the cell-free chromatin was derived. We use antibodies to capture chromatin that carry specific epigenetic information followed by sequencing of the underlying DNA fragments. We then use sophisticated computational tools to translate this data into clinical information.

In our publication in Nature Biotechnology we show that the cfChIP-seq technology  detects signals emanating from our tissues and immune system, which are used to diagnose a range of diseases including sensitive and early detection of colorectal cancer, and liver diseases. cfChIP-seq also detects patient-specific gene-level signatures that are used for subtyping cancer patients, which is an important  step towards personalized treatment selection.

Sadeh, R., Sharkia, I., Fialkoff, G. et al. ChIP-seq of plasma cell-free nucleosomes identifies gene expression programs of the cells of origin. Nat Biotechnol (2021).

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