Mathematical models of diffusion-constrained polymerase chain reactions: basis of high-throughput nucleic acid assays and simple self-organizing systems


John Aach and George M. Church

The Lipper Center for Computational Genetics, and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA

Correspondence should be addressed to G.C. (email)

Supplemental materials

Contents

  1. Abstract
  2. Supplemental Information
  3. Software
  4. Citing the article or this supplemental material
  5. Copyright
  6. Further Assistance

Abstract

DNA templates amplified by polymerase chain reaction in thin polyacrylamide gels form diffusion-constrained amplicons called "polonies" (polymerase colonies) that have been used to phase DNA haplotypes over long distances, to analyze RNA splice variants, and to assay other phenomena of biological interest. We present two sets of mathematical models, one for single polony growth (SPGM) and one for two polony interaction (TPIM), that will be used for optimization of polony technology. The models provide detailed predictions of polony yield, concentration profiles, growth of isolated polonies, and the interaction of neighboring polonies. The TPIM explains an experimental observation that nearby polonies deform against each other rather than interpenetrate, an effect important for optimizing polony protocols. However, the TPIM also predicts that polonies may invade each other with a complex geometry when sufficiently close. Polonies are also of interest as simple abiotic systems that exhibit lifelike properties of self-organization, growth, and development, and the models may also apply to biological phenomena involving propagation through tethering and diffusion. Our polony modeling software is available at our web site http://arep.med.harvard.edu/polony_models/.

Supplemental Information

Information on algorithms, yield power-law regressions, and other topics may be obtained here.

Full color figures may be obtained here. These may be useful if you only have access to a printed version of the published article (in which only gray scale versions of the figures appear).

Obtaining the polony model software

C source code for the six implemented models may be obtained here, along with instructions for compiling the programs and usage notes.

Citing the article or this supplemental material

Aach, J. and Church, G.M., 2004, Mathematical models of diffusion-constrained polymerase chain reactions: basis of high-throughput nucleic acid assays and simple self-organizing systems, J. Theor. Biol 228:31-46

Copyright

Copyright (c) 2004 by John Aach and the President and Fellows of Harvard University

Further Assistance

Contact John Aach



This page last updated by JA on 15 Apr 2004.