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Controlling uncertainty in aptamer selection.

Fabian Spill1, Zohar B Weinstein2, Atena Irani Shemirani3

  • 1Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Biomedical Engineering, Boston University, Boston MA 02215.

Proceedings of the National Academy of Sciences of the United States of America
|October 30, 2016
PubMed
Summary
This summary is machine-generated.

Discovering high-affinity aptamers using Systematic Evolution of Ligands by EXponential Enrichment (SELEX) is challenging. Our model reveals that even rare aptamers can impact SELEX dynamics, highlighting the role of chance and environmental factors.

Keywords:
SELEXaptamerevolutionary dynamicshybrid modelstochastic process

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Area of Science:

  • Biotechnology
  • Molecular Biology
  • Bioinformatics

Background:

  • Aptamer discovery via Systematic Evolution of Ligands by EXponential Enrichment (SELEX) is crucial for molecular recognition.
  • SELEX relies on evolutionary selection from diverse random pools, but outcomes can be variable and unpredictable.
  • Understanding the factors influencing SELEX efficiency is vital for optimizing aptamer selection.

Purpose of the Study:

  • To develop a stochastic hybrid model to simulate aptamer evolutionary selection.
  • To investigate the impact of uncertainties and environmental parameters on SELEX outcomes.
  • To identify strategies for improving the efficiency and speed of aptamer discovery.

Main Methods:

  • Development of a stochastic hybrid model for aptamer evolutionary dynamics.
  • Monte Carlo simulations to explore SELEX under varying conditions.
  • Analysis of population dynamics influenced by high-affinity aptamer presence.

Main Results:

  • Even single high-affinity aptamers can significantly influence population dynamics in SELEX.
  • Aptamer survival is highly dependent on stochastic events and chance.
  • Target concentration critically affects SELEX efficiency, with strategies identified to mitigate uncertainties.

Conclusions:

  • The stochastic model provides insights into the complex dynamics of aptamer SELEX.
  • Controlling environmental parameters like target concentration can enhance selection efficiency.
  • This work offers strategies to accelerate and improve the resource-intensive aptamer discovery process.