A Dynamical Biomolecular Neural Network

While much of synthetic biology was founded on the creation of reusable, standardized parts, there is now a growing interest in synthetic networks which can compute unique, specially-designed functions in order to recognize patterns or classify cells in-vivo. While artificial neural networks (ANNs) have long provided a mature mathematical framework to address this problem in-silico, their implementation becomes much more challenging in living systems. In this work, we propose a Biomolecular Neural Network (BNN), a dynamical chemical reaction network which faithfully implements ANN computations and which is unconditionally stable with respect to its parameters when composed into deeper networks. Our implementation emphasizes the usefulness of molecular sequestration for achieving negative weight values and a nonlinear "activation function" in its elemental unit, a biomolecular perceptron. We then discuss the application of BNNs to linear and nonlinear classification tasks, and draw analogies to other major concepts in modern machine learning research.

[1]  J. Ross,et al.  Chemical implementation and thermodynamics of collective neural networks. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[2]  A Hjelmfelt,et al.  Chemical implementation of neural networks and Turing machines. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[3]  Lulu Qian,et al.  Supporting Online Material Materials and Methods Figs. S1 to S6 Tables S1 to S4 References and Notes Scaling up Digital Circuit Computation with Dna Strand Displacement Cascades , 2022 .

[4]  Kurt Hornik,et al.  Approximation capabilities of multilayer feedforward networks , 1991, Neural Networks.

[5]  Vladimir Vapnik,et al.  Chervonenkis: On the uniform convergence of relative frequencies of events to their probabilities , 1971 .

[6]  Franco Blanchini,et al.  Molecular Titration Promotes Oscillations and Bistability in Minimal Network Models with Monomeric Regulators. , 2016, ACS synthetic biology.

[7]  Arvind Murugan,et al.  Temporal Pattern Recognition through Analog Molecular Computation. , 2018, ACS synthetic biology.

[8]  Georg Seelig,et al.  A molecular multi-gene classifier for disease diagnostics , 2018, Nature Chemistry.

[9]  Nicolas E. Buchler,et al.  On schemes of combinatorial transcription logic , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[10]  Christof Teuscher,et al.  Online Learning in a Chemical Perceptron , 2013, Artificial Life.

[11]  Elisa Franco,et al.  Dynamic Control of Aptamer-Ligand Activity Using Strand Displacement Reactions. , 2018, ACS synthetic biology.

[12]  George Cybenko,et al.  Approximation by superpositions of a sigmoidal function , 1989, Math. Control. Signals Syst..

[13]  Lulu Qian,et al.  Scaling up molecular pattern recognition with DNA-based winner-take-all neural networks , 2018, Nature.

[14]  Jehoshua Bruck,et al.  Neural network computation with DNA strand displacement cascades , 2011, Nature.

[15]  Alexandra M. Westbrook,et al.  Computational design of small transcription activating RNAs for versatile and dynamic gene regulation , 2017, Nature Communications.

[16]  Franco Blanchini,et al.  Structural Analysis of Biological Networks , 2014 .

[17]  Christian Cuba Samaniego,et al.  A molecular device for frequency doubling enabled by molecular sequestration , 2019, 2019 18th European Control Conference (ECC).

[18]  Richard Hans Robert Hahnloser,et al.  Digital selection and analogue amplification coexist in a cortex-inspired silicon circuit , 2000, Nature.

[19]  Niko Beerenwinkel,et al.  Automated Design of Synthetic Cell Classifier Circuits Using a Two-Step Optimization Strategy. , 2017, Cell systems.

[20]  Christof Teuscher,et al.  Feedforward Chemical Neural Network : An In Silico Chemical System , 2018 .

[21]  Alan R. Davidson,et al.  Anti-CRISPR: discovery, mechanism and function , 2017, Nature Reviews Microbiology.

[22]  Nicolas E. Buchler,et al.  Protein sequestration generates a flexible ultrasensitive response in a genetic network , 2009, Molecular systems biology.