Through the advancing technology, scientists increasingly search for tiny signs of cancer and other health issues in samples of the blood and urine of patients. These liquid biopsies are less invasive than a traditional biopsy and can provide information about what is happening throughout the body instead of just at a single site.
At present, University of Michigan Rogel Cancer Center's researchers has developed a new method for lifting the genetic fingerprints of tiny fragments of RNA found in blood plasma that are invisible to traditional techniques of RNA sequencing.
Muneesh Tewari, M.D., Ph.D., professor of internal medicine at the U-M Medical School and of biomedical engineering, a joint department of the Medical School and College of Engineering, said that they believe there are a wide variety of potential clinical applications. For instance, in cancer, they are excited about applying this approach to try to detect the earliest signs of autoimmune side-effects from immunotherapies. There's also the potential for early detection of cancer because there are long non-coding RNAs that are relatively specific to certain cancer types.
Tewari explained that the real innovation in this new study was recognizing that these other types of RNA were being missed because they had simple but crucial differences that prevented them from showing up in the blood plasma sequencing results. The scientist used an enzyme to tailor the ends of these fragments so they would show up in the sequencing. And that relatively simple step revealed that there are thousands of these new gene transcripts in the bloodstream.
The scientists had to figure out how to separate signal from noise, how to remove bits of irrelevant genetic material from bacterial and viral RNAs as well as from our genome which add noise to the data. When the sequences are short, they are matched to multiple places in the human genome by chance, and it is difficult to say which gene from where they are coming.
Explaining further, Tewari claimed that on the primary science side, now that they know there are thousands of these RNAs floating around in the bloodstream, it raises questions about why they are there and what function they may have. But the more immediate application is there they are now better able to read the human-transcriptome, the activity of genes throughout the body, in plasma samples which can give them new information about states of health and disease.
Tewari stressed the collaborative and cross-disciplinary nature of the work which required laboratory, computational and clinical expertise.
