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
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