Taking a tissue sample from an organ suspected of harboring a disease is a common diagnostic practice. Instead of relying on living tissue biopsies for answers, could analyzing dead cells be a less invasive, less painful way of understanding what’s going wrong with a patient?
Certain tissues undergo a constant cell turnover whereby some cells die only to be replaced by new ones. Take the skin, for example, where an estimated 40,000 skin cells are shed every day.
As dying cells reach the end of their shelf lives, their DNA begins to break down into fragments, some of which can end up in the circulatory system. According to researchers, these bits and pieces of DNA, known as cell-free DNA, are rich sources of information about the health of the organs they originated in.
All cells in the body have uniform and identical DNA sequences. However, the way the DNA is packaged and organized in cells derived from different tissues differs significantly. Proteins called histones pack and order DNA into repeated structural units known as nucleosomes. These histones contain chemical barcodes that code information on where the cells came from, their biological function and could even have molecular red flags that point to the presence of disease.
Researchers at Hebrew University have created a “barcode reader” to extract and analyze this epigenetic information from cell-free DNA present in blood samples, potentially putting an end to painful tissue biopsies for good.
“As a result of these scientific advancements, we understood that if this information is maintained within the DNA structure in the blood, we could use that data to determine the tissue source of dead cells and the genes that were active in those very cells,” said Nir Friedman, who led the research published in Nature Biotechnology.
“Based on those findings, we can uncover key details about the patient’s health.”
According to Friedman, these details include why a particular cell died, what disease a patient has and how the condition is progressing.
The technique, known as ChIP-seq, was validated in blood samples taken from a cohort of nearly 270 participants. ChIP-seq successfully detected anomalies in liver cells in patients with liver disease diagnoses. The scientists also picked up activations in cancer-associated genes in patients with metastatic colorectal carcinoma.
“We hope that this approach will allow for earlier diagnosis of disease and help physicians treat patients more effectively,” said Ronen Sadeh, another contributing author of the paper, who added that besides being non-invasive, ChIP-seq is also far cheaper than current diagnostic methods using biopsies.
“Recognizing the potential of this approach and how this technology can be so beneficial for diagnostic and therapeutic purposes, we set up the company Senseera which will be involved with clinical testing in partnership with major pharmaceutical companies with the goal of making this innovative approach available to patients,” said Sadeh.