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Distributed biological computation: from oscillators, logic gates and switches to a multicellular processor and neural computing applications

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Abstract

Ever since its foundational years, synthetic biology has been focused on the implementation of biological computing structures. In the beginning, engineered biological computation has mainly been based on uncoupled monoclonal cellular populations. Implementations of such computing structures were mostly inspired by digital electronic circuits and revealed many constraints that limited the advance of the field to relatively simple information processing structures. The focus has recently shifted towards the implementation of biological computing structures within coupled intercellular circuits composed of engineered cellular modules. These circuits have, however, advanced only to a certain point, namely to consist of a few engineered bacterial strains, which perform the computation. It is now time to make a transition from modules and relatively simple systems of biological processing structures to networks composing different strains each presenting a designated computing structure. In such networks, each strain is analogous to a logic chip on a breadboard circuit and is connected to other strains by means of intercellular communication mechanisms rather than copper wires. This analogy can be driven further to use a set of engineered biological modules to construct a complex computing system, such as a multicellular biological processor. We review the state of the art of distributed cellular computation, communication mechanisms, and computational analysis and design approaches for distributed biological computing. We demonstrate the potential next step in engineered biological computation by a proposal of a design of a multicellular biological processor. We demonstrate an analysis of the proposed computing network using in silico simulation and optimisation approaches. Finally, we discuss the potential applications of the reviewed distributed cellular computing structures to the field of neural computing.

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Availability of data and materials

The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.

Code availability

The code that can be used to reproduce the results reported in the article is available at https://github.com/roman-komac/distributed-bio-computing.

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Funding

The research was partially supported by the scientific research programme Pervasive Computing (P2-0359) financed by the Slovenian Research Agency in the years from 2013 to 2023 and by the basic research project CholesteROR in metabolic liver diseases (J1-9176) financed by the Slovenian Research Agency in the years from 2018 to 2021. The funding sources did not have any role in the study design, in the collection, analysis, and interpretation of data, in the writing of the manuscript, or in the decision to submit the manuscript for publication.

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  1. Faculty of Computer and Information Science, University of Ljubljana, Ljubljana, Slovenia

    Miha Moškon, Roman Komac, Nikolaj Zimic & Miha Mraz

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  1. Miha Moškon
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  2. Roman Komac
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  3. Nikolaj Zimic
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Contributions

M.M. reviewed the literature, outlined the processor topology, and wrote the manuscript. R.K. implemented the processor model and conducted its optimisation and analysis. M.M. and N.Z. provided critical feedback and helped shape the research, analysis and manuscript. All authors read and approved the final manuscript.

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Correspondence to Miha Moškon.

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Moškon, M., Komac, R., Zimic, N. et al. Distributed biological computation: from oscillators, logic gates and switches to a multicellular processor and neural computing applications. Neural Comput & Applic 33, 8923–8938 (2021). https://doi.org/10.1007/s00521-021-05711-6

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  • DOI: https://doi.org/10.1007/s00521-021-05711-6

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