Machine learning-guided directed evolution for protein engineering

Machine learning (ML)-guided directed evolution is a new paradigm for biological design that enables optimization of complex functions. ML methods use data to predict how sequence maps to function without requiring a detailed model of the underlying physics or biological pathways. To demonstrate ML-guided directed evolution, we introduce the steps required to build ML sequence-function models and use them to guide engineering, making recommendations at each stage. This review covers basic concepts relevant to using ML for protein engineering as well as the current literature and applications of this new engineering paradigm. ML methods accelerate directed evolution by learning from information contained in all measured variants and using that information to select sequences that are likely to be improved. We then provide two case studies that demonstrate the ML-guided directed evolution process. We also look to future opportunities where ML will enable discovery of new protein functions and uncover the relationship between protein sequence and function.Comment: Made significant revisions to focus on aspects most relevant to applying machine learning to speed up directed evolutio

Discovering Representations for Black-box Optimization

The encoding of solutions in black-box optimization is a delicate, handcrafted balance between expressiveness and domain knowledge -- between exploring a wide variety of solutions, and ensuring that those solutions are useful. Our main insight is that this process can be automated by generating a dataset of high-performing solutions with a quality diversity algorithm (here, MAP-Elites), then learning a representation with a generative model (here, a Variational Autoencoder) from that dataset. Our second insight is that this representation can be used to scale quality diversity optimization to higher dimensions -- but only if we carefully mix solutions generated with the learned representation and those generated with traditional variation operators. We demonstrate these capabilities by learning an low-dimensional encoding for the inverse kinematics of a thousand joint planar arm. The results show that learned representations make it possible to solve high-dimensional problems with orders of magnitude fewer evaluations than the standard MAP-Elites, and that, once solved, the produced encoding can be used for rapid optimization of novel, but similar, tasks. The presented techniques not only scale up quality diversity algorithms to high dimensions, but show that black-box optimization encodings can be automatically learned, rather than hand designed.Comment: Presented at GECCO 2020 -- v2 (Previous title 'Automating Representation Discovery with MAP-Elites'

Discrete and fuzzy dynamical genetic programming in the XCSF learning classifier system

A number of representation schemes have been presented for use within learning classifier systems, ranging from binary encodings to neural networks. This paper presents results from an investigation into using discrete and fuzzy dynamical system representations within the XCSF learning classifier system. In particular, asynchronous random Boolean networks are used to represent the traditional condition-action production system rules in the discrete case and asynchronous fuzzy logic networks in the continuous-valued case. It is shown possible to use self-adaptive, open-ended evolution to design an ensemble of such dynamical systems within XCSF to solve a number of well-known test problems

Neo: A Learned Query Optimizer

Query optimization is one of the most challenging problems in database systems. Despite the progress made over the past decades, query optimizers remain extremely complex components that require a great deal of hand-tuning for specific workloads and datasets. Motivated by this shortcoming and inspired by recent advances in applying machine learning to data management challenges, we introduce Neo (Neural Optimizer), a novel learning-based query optimizer that relies on deep neural networks to generate query executions plans. Neo bootstraps its query optimization model from existing optimizers and continues to learn from incoming queries, building upon its successes and learning from its failures. Furthermore, Neo naturally adapts to underlying data patterns and is robust to estimation errors. Experimental results demonstrate that Neo, even when bootstrapped from a simple optimizer like PostgreSQL, can learn a model that offers similar performance to state-of-the-art commercial optimizers, and in some cases even surpass them

Born to learn: The inspiration, progress, and future of evolved plastic artificial neural networks

Biological plastic neural networks are systems of extraordinary computational capabilities shaped by evolution, development, and lifetime learning. The interplay of these elements leads to the emergence of adaptive behavior and intelligence. Inspired by such intricate natural phenomena, Evolved Plastic Artificial Neural Networks (EPANNs) use simulated evolution in-silico to breed plastic neural networks with a large variety of dynamics, architectures, and plasticity rules: these artificial systems are composed of inputs, outputs, and plastic components that change in response to experiences in an environment. These systems may autonomously discover novel adaptive algorithms, and lead to hypotheses on the emergence of biological adaptation. EPANNs have seen considerable progress over the last two decades. Current scientific and technological advances in artificial neural networks are now setting the conditions for radically new approaches and results. In particular, the limitations of hand-designed networks could be overcome by more flexible and innovative solutions. This paper brings together a variety of inspiring ideas that define the field of EPANNs. The main methods and results are reviewed. Finally, new opportunities and developments are presented