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Embedding computation in biochemical environments incompatible with traditional electronics is expected to have wide-ranging impact in synthetic biology, medicine, nanofabrication and other fields. Natural biochemical systems are typically modeled by chemical reaction networks (CRNs), and CRNs can be used as a specification language for synthetic chemical computation. In this paper, we identify a class of CRNs called non-competitive (NC) whose equilibria are absolutely robust to reaction rates and kinetic rate law, because their behavior is captured solely by their stoichiometric structure. Unlike prior work on rate-independent CRNs, checking non-competition and using it as a design criterion is easy and promises robust output. We also present a technique to program NC-CRNs using well-founded deep learning methods, showing a translation procedure from rectified linear unit (ReLU) neural networks to NC-CRNs. In the case of binary weight ReLU networks, our translation procedure is surprisingly tight in the sense that a single bimolecular reaction corresponds to a single ReLU node and vice versa. This compactness argues that neural networks may be a fitting paradigm for programming rate-independent chemical computation. As proof of principle, we demonstrate our scheme with numerical simulations of CRNs translated from neural networks trained on traditional machine learning datasets (IRIS and MNIST), as well as tasks better aligned with potential biological applications including virus detection and spatial pattern formation.

Embedding computation in molecular contexts incompatible with traditional electronics is expected to have wide ranging impact in synthetic biology, medicine, nanofabrication and other fields. A key remaining challenge lies in developing programming paradigms for molecular computation that are well-aligned with the underlying chemical hardware and do not attempt to shoehorn ill-fitting electronics paradigms. We discover a surprisingly tight connection between a popular class of neural networks (binary-weight ReLU aka BinaryConnect) and a class of coupled chemical reactions that are absolutely robust to reaction rates. The robustness of rate-independent chemical computation makes it a promising target for bioengineering implementation. We show how a BinaryConnect neural network trained in silico using well-founded deep learning optimization techniques, can be compiled to an equivalent chemical reaction network, providing a novel molecular programming paradigm. We illustrate such translation on the paradigmatic IRIS and MNIST datasets. Toward intended applications of chemical computation, we further use our method to generate a chemical reaction network that can discriminate between different virus types based on gene expression levels. Our work sets the stage for rich knowledge transfer between neural network and molecular programming communities.

This paper introduces the MCML approach for empirically studying the learnability of relational properties that can be expressed in the well-known software design language Alloy. A key novelty of MCML is quantification of the performance of and semantic differences among trained machine learning (ML) models, specifically decision trees, with respect to entire (bounded) input spaces, and not just for given training and test datasets (as is the common practice). MCML reduces the quantification problems to the classic complexity theory problem of model counting, and employs state-of-the-art model counters. The results show that relatively simple ML models can achieve surprisingly high performance (accuracy and F1-score) when evaluated in the common setting of using training and test datasets - even when the training dataset is much smaller than the test dataset - indicating the seeming simplicity of learning relational properties. However, MCML metrics based on model counting show that the performance can degrade substantially when tested against the entire (bounded) input space, indicating the high complexity of precisely learning these properties, and the usefulness of model counting in quantifying the true performance.

Formal methods have enabled breakthroughs in many fields, such as in hardware verification, machine learning and biological systems. The key object of interest in systems biology, synthetic biology, and molecular programming is chemical reaction networks (CRNs) which formalizes coupled chemical reactions in a well-mixed solution. CRNs are pivotal for our understanding of biological regulatory and metabolic networks, as well as for programming engineered molecular behavior. Although it is clear that small CRNs are capable of complex dynamics and computational behavior, it remains difficult to explore the space of CRNs in search for desired functionality. We use Alloy, a tool for expressing structural constraints and behavior in software systems, to enumerate CRNs with declaratively specified properties. We show how this framework can enumerate CRNs with a variety of structural constraints including biologically motivated catalytic networks and metabolic networks, and seesaw networks motivated by DNA nanotechnology. We also use the framework to explore analog function computation in rate-independent CRNs. By computing the desired output value with stoichiometry rather than with reaction rates (in the sense that $X \to Y+Y$ computes multiplication by $2$), such CRNs are completely robust to the choice of reaction rates or rate law. We find the smallest CRNs computing the max, minmax, abs and ReLU (rectified linear unit) functions in a natural subclass of rate-independent CRNs where rate-independence follows from structural network properties.

Rapid advancements in deep learning have led to many recent breakthroughs. While deep learning models achieve superior performance, often statistically better than humans, their adoption into safety-critical settings, such as healthcare or self-driving cars is hindered by their inability to provide safety guarantees or to expose the inner workings of the model in a human understandable form. We present Mo\"ET, a novel model based on Mixture of Experts, consisting of decision tree experts and a generalized linear model gating function. Thanks to such gating function the model is more expressive than the standard decision tree. To support non-differentiable decision trees as experts, we formulate a novel training procedure. In addition, we introduce a hard thresholding version, Mo\"ETH, in which predictions are made solely by a single expert chosen via the gating function. Thanks to that property, Mo\"ETH allows each prediction to be easily decomposed into a set of logical rules in a form which can be easily verified. While Mo\"ET is a general use model, we illustrate its power in the reinforcement learning setting. By training Mo\"ET models using an imitation learning procedure on deep RL agents we outperform the previous state-of-the-art technique based on decision trees while preserving the verifiability of the models. Moreover, we show that Mo\"ET can also be used in real-world supervised problems on which it outperforms other verifiable machine learning models.

Due to its potential to improve programmer productivity and software quality, automated program repair has been an active topic of research. Newer techniques harness neural networks to learn directly from examples of buggy programs and their fixes. In this work, we consider a recently identified class of bugs called variable-misuse bugs. The state-of-the-art solution for variable misuse enumerates potential fixes for all possible bug locations in a program, before selecting the best prediction. We show that it is beneficial to train a model that jointly and directly localizes and repairs variable-misuse bugs. We present multi-headed pointer networks for this purpose, with one head each for localization and repair. The experimental results show that the joint model significantly outperforms an enumerative solution that uses a pointer based model for repair alone., Comment: ICLR 2019

Synthetic biology is a rapidly emerging research area, with expected wide-ranging impact in biology, nanofabrication, and medicine. A key technical challenge lies in embedding computation in molecular contexts where electronic micro-controllers cannot be inserted. This necessitates effective representation of computation using molecular components. While previous work established the Turing-completeness of chemical reactions, defining representations that are faithful, efficient, and practical remains challenging. This paper introduces CRN++, a new language for programming deterministic (mass-action) chemical kinetics to perform computation. We present its syntax and semantics, and build a compiler translating CRN++ programs into chemical reactions, thereby laying the foundation of a comprehensive framework for molecular programming. Our language addresses the key challenge of embedding familiar imperative constructs into a set of chemical reactions happening simultaneously and manipulating real-valued concentrations. Although some deviation from ideal output value cannot be avoided, we develop methods to minimize the error, and implement error analysis tools. We demonstrate the feasibility of using CRN++ on a suite of well-known algorithms for discrete and real-valued computation. CRN++ can be easily extended to support new commands or chemical reaction implementations, and thus provides a foundation for developing more robust and practical molecular programs.