PLoS Computational Biology (Sep 2020)

A compiler for biological networks on silicon chips.

  • J Kyle Medley,
  • Jonathan Teo,
  • Sung Sik Woo,
  • Joseph Hellerstein,
  • Rahul Sarpeshkar,
  • Herbert M Sauro

DOI
https://doi.org/10.1371/journal.pcbi.1008063
Journal volume & issue
Vol. 16, no. 9
p. e1008063

Abstract

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The explosive growth in semiconductor integrated circuits was made possible in large part by design automation software. The design and/or analysis of synthetic and natural circuits in living cells could be made more scalable using the same approach. We present a compiler which converts standard representations of chemical reaction networks and circuits into hardware configurations that can be used to simulate the network on specialized cytomorphic hardware. The compiler also creates circuit-level models of the target configuration, which enhances the versatility of the compiler and enables the validation of its functionality without physical experimentation with the hardware. We show that this compiler can translate networks comprised of mass-action kinetics, classic enzyme kinetics (Michaelis-Menten, Briggs-Haldane, and Botts-Morales formalisms), and genetic repressor kinetics, thereby allowing a large class of models to be transformed into a hardware representation. Rule-based models are particularly well-suited to this approach, as we demonstrate by compiling a MAP kinase model. Development of specialized hardware and software for simulating biological networks has the potential to enable the simulation of larger kinetic models than are currently feasible or allow the parallel simulation of many smaller networks with better performance than current simulation software.