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ABOUT THE AUTHOR
Dr. Steven Pelech is the Founder,
President, and Chief Scientific
Officer of Kinexus Bioinformatics
Corporation, and concurrently a
full professor in the Department of
Medicine at the University of British
Columbia. He was formerly the
founder and president of Kinetek
Pharmaceuticals. He has authored
more than 230 scientific papers
and created the SigNET on-line
Knowledge-bank.
Dr. Steven Pelech
Founder, President & Chief Scientific Officer
documented in proteins, with phosphorylation as the
predominant reversible regulatory mechanism. Over 85% of
the proteome is known to be phosphorylatable at over
250,000 sites, but the actual number of phosphosites
appears to be closer to a million. The occurrence of these
and other modifications in proteins represent a rich source
of biomarkers that may correlate better with the
development of pathologies.
Most sites of known protein modification were originally
revealed by mass spectrometry (MS). However, apart from
being very expensive, MS requires milligram amount of
biological sample material and is finicky for reliable
detection of desired target proteins. For example, out of
some 3000 phosphosites in proteins that have been well
documented to be functionally important in the scientific
literature, about 22% have not been reported in any MS
studies, whereas another 16% were documented in only one
of thousands of MS analyses that had been performed.
Antibodies have been well proven to be reliable and
effective probes for the detection and quantification of
specific proteins for their present and modification states.
Over a million different antibodies against diverse proteins
are presently commercially available. Furthermore, the
printing of antibodies as individual microdots on
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microscope slide-sized chips with densities exceeding 5000
spots per chip has paved the way for biomarker discovery
that is easily translatable into the development of routine
diagnostic tests. Biomarker antibodies can readily be
re-deployed into other tried and true platforms such as
immunoblotting, ELISA, and immunohistochemistry.
Problems with sample preparation, high background issues,
and low sensitivity of detection initially hampered the wide-
spread adoption of antibody microarrays. However, recent
breakthroughs on all of these fronts have poised antibody
microarrays to become the most versatile, reproducible, and
cost-effective tools in the foreseeable future for biomarker
discovery, using as little as 25 microgram amounts of
protein samples from crude, unfractionated lysates from
cells, tissues, and bio fluids. High content antibody
microarrays can identify the most appropriate and robust
panel of biomarkers. When used to probe lysate microarrays
printed instead with hundreds of patient specimen samples
on each slide, these biomarker antibodies can provide
accurate, comprehensive and economical diagnoses for
diseases and for the monitoring of the effectiveness of
therapeutic treatments.