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A mathematical model for a biphasic DNA amplification reaction.

Danielle Ciesielski1, Burcu Özay2, Stephanie McCalla2

  • 11 Department of Mathematical Sciences, Montana State University , Bozeman, MT 59715 , USA.

Journal of the Royal Society, Interface
|May 30, 2019
PubMed
Summary

A new ultrasensitive DNA amplification reaction (UDAR) shows higher yields and biphasic behavior than EXPAR. A mathematical model explains UDAR

Keywords:
DNA amplificationbiochemical networkbiphasickinetic model

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Area of Science:

  • Molecular Biology
  • Biophysics
  • Biotechnology

Background:

  • Isothermal DNA amplification is crucial for analyte detection and DNA circuits.
  • Exponential amplification reaction (EXPAR) amplifies short DNA oligonucleotides exponentially.
  • A modified technique, ultrasensitive DNA amplification reaction (UDAR), exhibits enhanced performance.

Purpose of the Study:

  • To develop the first mathematical model for ultrasensitive DNA amplification reaction (UDAR).
  • To understand the mechanisms behind UDAR's biphasic amplification and high DNA yield.
  • To elucidate the behavior of EXPAR and other nucleic acid amplification reactions.

Main Methods:

  • Developing a mathematical model for UDAR based on four key reaction mechanisms.
  • Simulating UDAR to reproduce experimentally observed biphasic amplification.
  • Analyzing the necessity of each proposed mechanism for biphasic behavior.

Main Results:

  • The mathematical model successfully reproduces the experimentally observed biphasic amplification of UDAR.
  • Three specific mechanisms are identified as essential for the biphasic behavior.
  • The model provides insights into high-gain, switch-like DNA output from low DNA input concentrations.

Conclusions:

  • The developed mathematical model accurately describes UDAR's unique amplification profile.
  • Positively cooperative binding, template deactivation/recycling, and polymerase sequestration are critical for UDAR.
  • This work offers a framework for understanding and optimizing various nucleic acid amplification strategies.