In year three of the French revolution, a law was enacted to realize the rallying cry, “un roi, une loi, un poids, et une mesure” (One king, one law, one weight, and one measure). This became the introduction of the metric system. The one king idea may have been dropped shortly after, but the idea of one system of measurement has survived. In all of science, our imagination is constrained by what we can measure and to advance the understanding it is absolutely necessary that everyone is talking about the same thing. However, this should not be mis-interpreted as meaning that we are measuring or understanding everything that needs to be known.
Beyond the Canonical: Why Protein Measurement is Missing the Pathology
This is true when it comes to the science of proteomics. To advance the science it has been necessary to define canonical forms for protein measurement. The definition of a canonical form is based on our capacity for protein measurement. As such, the key is the amino acid sequence. Traditional proteomics (LC-MS/MS) has succeeded due to the creation of software that solves possibilities by relying on reference databases of protein sequences. The ability to identify isoforms and post-translational modifications has improved through the addition of information to the database.
High-plex proteomics platforms improve upon traditional ones by translating information about proteins abundance to DNA abundance. This allows for direct measurement by qPCR or next generation sequencing (NGS). Although these platforms can read multiple proteins at a time, they have been built in a traditional way by characterizing the binding of one probe to the canonical form of a protein. However, there is a flaw because most patho-physiologies are not caused by the canonical forms of proteins. They are caused by deviation from these forms. For Example, a sign of diabetes is the hyper-glycosylation of proteins in blood and Alzheimer’s is defined by mis-cleavage and mis-folding events.
The Aptamarker Platform: Capturing the Full Proteoform Spectrum
To address this need we have developed the Aptamarker platform. We have reinvented aptamer selection by designing libraries with a reduced number of random nucleotides interspersed by fixed sequences. This enables us to apply the same set of millions of probes to different biofluid or tissue samples. Subsequently, we can characterize the binding abundance of all these probes in one NGS analysis. This data contains all the information regarding canonical forms of proteins as well as information regarding their non-canonical forms. We are moving the science of proteomics ahead by moving our capacity to measure proteins beyond defined canonical databases.
“One king” may be returning in the form of artificial intelligence, the question for the future is what this means for “one measurement”.
To learn more about the Aptamarker platform and to investigate how you could become involved in a pilot study please visit us at neoventures-eu.com.
Photo credit: L. F. Labrousse (engraver). J. P. Delion, Paris (publisher)