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 recent publication in Nature Biotechnology we show that the cfChIP-seq technology can detect cell-free chromatin tissue of origin including contribution from rare cells and from the population of special platelets generating cells in the bone marrow. We demonstrate that the technology detects various diseases including cancers in an extreme sensitivity. We also show that cfChIP-seq can identify patient-specific gene-expression like signatures that have the potential to promote a more personalized treatment.
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).