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Published November 19, 2021 | Published + Supplemental Material
Journal Article Open

A Loser-Take-All DNA Circuit

Abstract

DNA-based neural networks are a type of DNA circuit capable of molecular pattern recognition tasks. Winner-take-all DNA networks have been developed to scale up the complexity of molecular pattern recognition with a simple molecular implementation. This simplicity was achieved by replacing negative weights in individual neurons with lateral inhibition and competition across neurons, eliminating the need for dual-rail representation. Here we introduce a new type of DNA circuit that is called loser-take-all: an output signal is ON if and only if the corresponding input has the smallest analog value among all inputs. We develop a DNA strand-displacement implementation of loser-take-all circuits that is cascadable without dual-rail representation, maintaining the simplicity desired for scalability. We characterize the impact of effective signal concentrations and reaction rates on the circuit performance, and derive solutions for compensating undesired signal loss and rate differences. Using these approaches, we successfully demonstrate a three-input loser-take-all circuit with nine unique input combinations. Complementary to winner-take-all, loser-take-all DNA circuits could be used for recognition of molecular patterns based on their least similarities to a set of memories, allowing classification decisions for patterns that are extremely noisy. Moreover, the design principle of loser-take-all could be more generally applied in other DNA circuit implementations including k-winner-take-all.

Additional Information

© 2021 The Authors. Published by American Chemical Society. Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) Received: July 10, 2021; Published: October 8, 2021. K.R.R. and N.S. were supported by Caltech internal funds for BE/CS 196, a course on design and construction of programmable molecular systems. K.R.R. was also supported by a Bob and Carole Chapman Minority SURF fellowship and a NSF award (1908643). N.S. was also supported by a NIH/NRSA training grant (T32 GM07616). L.Q. was supported by a NSF award (1908643). The authors thank K. M. Cherry, S. J. Buse, and E. Winfree for discussions and comments. Author Contributions: K.R.R. and N.S. contributed equally. K.R.R. initiated the project and wrote the first draft of the manuscript; N.S. performed the experiments; all authors designed the experiments, analyzed the data, and edited the manuscript; L.Q. guided the project. The authors declare no competing financial interest.

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Published - acssynbio.1c00318.pdf

Supplemental Material - sb1c00318_si_001.pdf

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Additional details

Created:
September 15, 2023
Modified:
December 22, 2023