This is the first of several blogs we will share on our new Neomer process. The image above can be compared to a dilemma in traditional aptamer selection: are the aptamers that are enriching the product of the selection process (I would vote for the wine glass for this representation), or the product of bias of the selection process (the faces impinging on the wine glass), and how do we tell sequences apart?
There are many possible reasons for process bias on aptamer selection, but probably the most clear is the potential for PCR bias. This is evinced in at least two ways in sequencing data, a) aptamers that show high copy number enrichment over selection rounds but little or no binding to the target, and b) aptamers that show high copy number enrichment on both positive and negative selections. The latter observation leads to non-consideration of these aptamers but still it is annoying, why are they doing this?
It is clear that the more secondary structure in an aptamer the less well it is amplified. This often runs counter to optimum aptamer selection as strong, stable secondary structure is often a defining feature of good aptamers. PCR bias in aptamer selection is manifested as an exponential factor that is multiplied across selection rounds. Binding affinity and specificity is only a linear factor and thus can be easily overcome by PCR bias.
In our Neomer aptamer discovery method we overcome this problem in two ways.
One, we can perform as little as a single round of selection, thus differences in PCR efficiency are not accumulated. Two, given that we can start selection with different aliquots of the identical naïve starting library, we can run a negative control selection without target and use this to normalize for all selection effects on individual aptamer frequency, including PCR bias.
In our next blog we will discuss the statistical basis of Neomer analysis, and how this adds strength to the removal of bias and enables identification of desirable aptamers from the selection data. With the Neomer method we can parse the wine glass and most importantly, the wine within it from artefacts that were part of the process.
Le Dr. Gregory Penner a suivi une formation académique qui mêlait une théorie très pratique en matière de sélection végétale à la biologie moléculaire. Il a utilisé cette combinaison de biologie et de mathématiques pour développer et diriger une équipe de recherche en biotechnologie céréalière au sein du gouvernement du Canada, puis en tant que leader mondial de la recherche chez Monsanto Inc. Il a été un leader d'opinion en développement d'aptamères à l'échelle mondiale au cours des vingt dernières années en tant que PDG et président de NeoVentures. Il a dirigé cette entreprise vers la stabilité financière sans investissement extérieur grâce à une approche intégrée de la découverte et de la commercialisation des aptamères. En 2015, il a co-fondé une deuxième entreprise, NeoNeuro à Paris en France, axée sur une approche innovante pour identifier les Aptamarkers pour les maladies complexes.
Connectez-vous avec le Dr. Penner sur LinkedIn ou pour les mises à jour de l'entreprise, suivez NeoVentures.
French 
English 
Spanish