A Molecular Implementation of the Least Mean Squares Estimator

In order to function reliably, synthetic molecular circuits require mechanisms that allow them to adapt to environmental disturbances. Least mean squares (LMS) schemes, such as commonly encountered in signal processing and control, provide a powerful means to accomplish that goal. In this paper we show how the traditional LMS algorithm can be implemented at the molecular level using only a few elementary biomolecular reactions. We demonstrate our approach using several simulation studies and discuss its relevance to synthetic biology.Comment: Molecular circuits, synthetic biology, least mean squares estimator, adaptive system

Synthetic biology routes to bio-artificial intelligence

The design of synthetic gene networks (SGNs) has advanced to the extent that novel genetic circuits are now being tested for their ability to recapitulate archetypal learning behaviours first defined in the fields of machine and animal learning. Here, we discuss the biological implementation of a perceptron algorithm for linear classification of input data. An expansion of this biological design that encompasses cellular 'teachers' and 'students' is also examined. We also discuss implementation of Pavlovian associative learning using SGNs and present an example of such a scheme and in silico simulation of its performance. In addition to designed SGNs, we also consider the option to establish conditions in which a population of SGNs can evolve diversity in order to better contend with complex input data. Finally, we compare recent ethical concerns in the field of artificial intelligence (AI) and the future challenges raised by bio-artificial intelligence (BI)

Learning without neurons in physical systems

Learning is traditionally studied in biological or computational systems. The power of learning frameworks in solving hard inverse-problems provides an appealing case for the development of `physical learning' in which physical systems adopt desirable properties on their own without computational design. It was recently realized that large classes of physical systems can physically learn through local learning rules, autonomously adapting their parameters in response to observed examples of use. We review recent work in the emerging field of physical learning, describing theoretical and experimental advances in areas ranging from molecular self-assembly to flow networks and mechanical materials. Physical learning machines provide multiple practical advantages over computer designed ones, in particular by not requiring an accurate model of the system, and their ability to autonomously adapt to changing needs over time. As theoretical constructs, physical learning machines afford a novel perspective on how physical constraints modify abstract learning theory.Comment: 25 pages, 6 figure

COEL: A Cloud-Based Reaction Network Simulator

Chemical Reaction Networks (CRNs) are a formalism to describe the macroscopic behavior of chemical systems. We introduce COEL, a web- and cloud-based CRN simulation framework, which does not require a local installation, runs simulations on a large computational grid, provides reliable database storage, and offers a visually pleasing and intuitive user interface. We present an overview of the underlying software, the technologies, and the main architectural approaches employed. Some of COEL’s key features include ODE-based simulations of CRNs and multicompartment reaction networks with rich interaction options, a built-in plotting engine, automatic DNA-strand displacement transformation and visualization, SBML/Octave/Matlab export, and a built-in genetic-algorithm- based optimization toolbox for rate constants. COEL is an open-source project hosted on GitHub (doi:10.5281/zenodo.46544), which allows interested research groups to deploy it on their own sever. Regular users can simply use the web instance at no cost at coel-sim.org. The framework is ideally suited for a collaborative use in both research and education

Logic Circuits Based on Extended Molecular Spider Systems

Spatial locality brings the advantages of computation speed-up and sequence reuse to molecular computing. In particular, molecular walkers that undergo localized re- actions are of interest for implementing logic computations at the nanoscale. We use molecular spider walkers to implement logic circuits. We develop an extended multi- spider model with a dynamic environment wherein signal transmission is triggered via localized reactions, and use this model to implement three basic gates (AND, OR, and NOT) and a cascading mechanism. We develop an algorithm to automatically generate the layout of the circuit. We use a kinetic Monte Carlo algorithm to simulate circuit computations, and we analyze circuit complexity: our design scales linearly with formula size and has a logarithmic time complexity

Theory and Practice of Computing with Excitable Dynamics

Reservoir computing (RC) is a promising paradigm for time series processing. In this paradigm, the desired output is computed by combining measurements of an excitable system that responds to time-dependent exogenous stimuli. The excitable system is called a reservoir and measurements of its state are combined using a readout layer to produce a target output. The power of RC is attributed to an emergent short-term memory in dynamical systems and has been analyzed mathematically for both linear and nonlinear dynamical systems. The theory of RC treats only the macroscopic properties of the reservoir, without reference to the underlying medium it is made of. As a result, RC is particularly attractive for building computational devices using emerging technologies whose structure is not exactly controllable, such as self-assembled nanoscale circuits. RC has lacked a formal framework for performance analysis and prediction that goes beyond memory properties. To provide such a framework, here a mathematical theory of memory and information processing in ordered and disordered linear dynamical systems is developed. This theory analyzes the optimal readout layer for a given task. The focus of the theory is a standard model of RC, the echo state network (ESN). An ESN consists of a fixed recurrent neural network that is driven by an external signal. The dynamics of the network is then combined linearly with readout weights to produce the desired output. The readout weights are calculated using linear regression. Using an analysis of regression equations, the readout weights can be calculated using only the statistical properties of the reservoir dynamics, the input signal, and the desired output. The readout layer weights can be calculated from a priori knowledge of the desired function to be computed and the weight matrix of the reservoir. This formulation explicitly depends on the input weights, the reservoir weights, and the statistics of the target function. This formulation is used to bound the expected error of the system for a given target function. The effects of input-output correlation and complex network structure in the reservoir on the computational performance of the system have been mathematically characterized. Far from the chaotic regime, ordered linear networks exhibit a homogeneous decay of memory in different dimensions, which keeps the input history coherent. As disorder is introduced in the structure of the network, memory decay becomes inhomogeneous along different dimensions causing decoherence in the input history, and degradation in task-solving performance. Close to the chaotic regime, the ordered systems show loss of temporal information in the input history, and therefore inability to solve tasks. However, by introducing disorder and therefore heterogeneous decay of memory the temporal information of input history is preserved and the task-solving performance is recovered. Thus for systems at the edge of chaos, disordered structure may enhance temporal information processing. Although the current framework only applies to linear systems, in principle it can be used to describe the properties of physical reservoir computing, e.g., photonic RC using short coherence-length light

Biomolecular System Design: Architecture, Synthesis, and Simulation

The advancements in systems and synthetic biology have been broadening the range of realizable systems with increasing complexity both in vitro and in vivo. Systems for digital logic operations, signal processing, analog computation, program flow control, as well as those composed of different functions – for example an on-site diagnostic system based on multiple biomarker measurements and signal processing – have been realized successfully. However, the efforts to date tend to tackle each design problem separately, relying on ad hoc strategies rather than providing more general solutions based on a unified and extensible architecture, resulting in long development cycle and rigid systems that require redesign even for small specification changes.Inspired by well-tested techniques adopted in electronics design automation (EDA), this work aims to remedy current design methodology by establishing a standardized, complete flow for realizing biomolecular systems. Given a behavior specification, the flow streamlines all the steps from modeling, synthesis, simulation, to final technology mapping onto implementing chassis. The resulted biomolecular systems of our design flow are all built on top of an FPGA-like reconfigurable architecture with recurring modules. Each module is designed the function of eachmodule depends on the concentrations of assigned auxiliary species acting as the “tuning knobs.” Reconfigurability not only simplifies redesign for altered specification or post-simulation correction, but also makes post-manufacture fine-tuning – even after system deployment – possible. This flexibility is especially important in synthetic biology due to the unavoidable variations in both the deployed biological environment and the biomolecular reactions forming the designed system.In fact, by combining the system’s reconfigurability and neural network’s self-adaptiveness through learning, we further demonstrate the high compatibility of neuromorphic computation to our proposed architecture. Simulation results verified that with each module implementing a neuron of selected model (ex. spike-based, threshold-gate-like, etc.), accompanied by an appropriate choice of reconfigurable properties (ex. threshold value, synaptic weight, etc.), the system built from our proposed flow can indeed perform desired neuromorphic functions

Memristors for the Curious Outsiders

We present both an overview and a perspective of recent experimental advances and proposed new approaches to performing computation using memristors. A memristor is a 2-terminal passive component with a dynamic resistance depending on an internal parameter. We provide an brief historical introduction, as well as an overview over the physical mechanism that lead to memristive behavior. This review is meant to guide nonpractitioners in the field of memristive circuits and their connection to machine learning and neural computation.Comment: Perpective paper for MDPI Technologies; 43 page