Jerusalem Researchers Develop a Potential Replacement for Some Invasive Biopsies

Biopsies, in which a sample of tissue is extracted from the patient for analysis to diagnose disease, is a common tool used by a variety of physicians. But this approach has several drawbacks – it can be painful; doesn’t always extract the diseased tissue; and it can be used only when the disease is in sufficiently advanced stage, making it, in some cases, too late for intervention.  

These concerns have encouraged researchers to find less invasive and more accurate options for diagnoses. Now, a new blood test developed by researchers at the Hebrew University of Jerusalem (HUJI) has the potential to diagnose a wide array of disorders including cancers, liver diseases, immune disorders and more.  Extremely accurate, the test can report on the exact state and location of the disease without need for invasive and painful biopsies.

Prof. Nir Friedman and Dr. Ronen Sadeh of HUJI” Life Sciences Institute and School of Computer Engineering have just published a study in the prestigious journal Nature Biotechnology under the title “ChIP-seq of plasma cell-free nucleosomes identifies gene expression programs of the cells of origin” that shows how a wide range of diseases can be detected through a simple blood test.  

The test makes it possible for lab technicians to identify and determine the state of the dead cells throughout the body and then diagnose various diseases including cancers and disorders of the heart and liver. The test is even able to identify specific markers that may differ among patients suffering from the same types of tumorous growths – a feature that has the potential to help physicians develop personalized treatments for specific patients.

The test relies on a natural process in which millions of cells in our body die and are replaced by new cells every day. When cells die, their DNA is fragmented and some of these DNA fragments reach the blood and can be detected by DNA sequencing methods. But, since all our cells have the same DNA sequence, simply sequencing the DNA cannot identify from which cells it originated. 

While the DNA sequence is identical between cells, the way the DNA is organized in the cell is substantially different. The DNA is packaged into nucleosomes – small repeating structures that contain specialized proteins called histones. The cells write a unique chemical code on the histone proteins that can identify the cell and even the biological and pathological processes that are going on inside. In recent years, numerous studies have successfully developed a process in which this information can  be identified and thus reveal abnormal cell activity.   

A new approach advanced by Friedman and can precisely read this information from DNA in the blood and use it to determine the nature of the disease or tumor, exactly where in the body it’s found and even how far developed it is.  

The approach relies on analysis of epigenetic information (heritable changes in gene expression that do not involve changes to the underlying DNA sequence within the cell) – a method which has been increasingly fine-tuned in recent years.  

“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. Based on those findings, we can uncover key details about the patient’s health,” Friedman added.  “We are able to better understand why the cells died, whether it’s an infection or cancer and based on that be better positioned to determine how the disease is developing.”

Along with the clear diagnostic benefits of this process, the test is also non-invasive and far less expensive than traditional biopsies, Sadeh said. “We hope that this approach will allow for earlier diagnosis of disease and help physicians to treat patients more effectively.  Recognizing the potential of this approach and how this technology can be so beneficial for diagnostic and therapeutic purposes, we a company named Senseera that will perform clinical testing in partnership with major pharmaceutical companies with the goal of making this innovative approach available to patients.”