New Cutting Edge Proteomic Technology Key to Improved Biomarker Discovery

Biomarkers are the molecules found in blood, urine, body fluids and tissues that serve as distinguishing signs of normal or abnormal processes, and can thereby provide clinicians with key Information about diseases and treatments. The accessibility of proteins in tissues and bodily fluids has led to extensive research to identify new biomarkers.

BIDMC’s Genomics and Proteomics Core recently acquired a new state-of-the-art proteomic technology called SOMAScan, which provides scientists with powerful new applications for ultra-sensitive protein biomarker discovery. BIDMC is the only certified facility in the Boston area to offer scientists this advanced technology.

“There are many different applications for biomarkers today,” says Towia Libermann, PhD, Director of the Genomics, Proteomics, Bioinformatics and Systems Biology Center at BIDMC and of the Cancer Proteomics Core for the Dana Farber/Harvard Cancer Center. “Biomarkers can help us figure out how to best manage patients, how to stratify patients, how to diagnose disease, how to monitor patient responses to therapies, and how to predict therapeutic response and outcomes.

A Complex System

The proteome is complex and proteomics encompasses a range of information that is broader than genomics, the large scale study of the human genome. Consider that a single gene can encode multiple proteins, and the human genome contains approximately 21,000 protein-encoding genes. Moreover, proteins are continuously and rapidly undergoing modifications that change their structure and function, frequently generating dozens of functionally different products from a single protein.

The total number of different forms of proteins in human cells remains unknown, but is estimated to be between 250,000 and 1 million. Furthermore, while the genome is relatively static, proteins are constantly undergoing changes, and exist in a wide range of different concentrations within the body. “Proteins are the primary effector molecules performing most of the reactions that result in changes related to disease onset and are the targets for many drugs used to treat diseases, “ explains Libermann. “Most importantly, protein levels in the blood are used in a majority of diagnostic tests.”

Improved Technology

The new SOMAScan proteomics platform offers scientists and clinicians an innovative tool with unprecedented power to discover new disease biomarkers and to understand the different pathophysiological processes involved in disease development and progression.

“Proteomics technology enables us to analyze a variety of biospecimens for their protein contents and accurately measure the concentrations of these proteins,” says Libermann. “But the issue with existing proteomics technologies has been that you are either able to get sensitive detection of just a few proteins or are able to get detection of many proteins -- but with low sensitivity. Because most disease biomarkers are expressed at very low levels in blood or urine [the preferred biofluids for diagnostic tests] it is critical to find a platform that can detect very low expression levels of proteins and can do this for many proteins that may be of interest as biomarkers.”

The SOMAscan technology incorporates unique reagents called SOMAmers (a new class of superior, high affinity protein-binding modified aptamers) to rapidly measure over 1,300 proteins across a wide range of concentrations (from low-abundant to high-abundant proteins) and in small volumes of various biological sample types with high reproducibility and high specificity. This is the only technology that can currently achieve this.

“Proteomics technologies such as SOMAscan are rapidly identifying and validating diagnostic, predictive and prognostic biomarkers for the prevention, detection, management and treatment of a range of diseases. Such a comprehensive protein analysis may enable the simultaneous diagnosis of multiple health parameters with a single test, which would be a major advance in personalized medicine,” said Libermann.

New Biomarkers Identified

“BIDMC proteomics as well as genomic studies have already identified candidate biopsy, blood, urine and cerebrospinal fluid biomarkers for a wide range of disease areas from cancer to inflammatory bowel disease, and autism to liver disease,” notes Libermann.

“In each instance we were able to confirm prior findings and to obtain new insights into the origins or progression of the disease,” he explains. For example, a new study by Libermann, currently published online in the journal Oncotarget, has identified highly accurate biomarkers for the detection of pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer which is largely incurable due to late diagnosis and lack of effective therapies. “We have identified and validated a 5-gene biomarker panel for discriminating PDAC and precursor lesions from non-malignant tissue. This could help lead to earlier or differential diagnosis, earlier intervention, as well as risk stratification in clinical trials.”