Molecular design and synthesis planning are two critical steps in the process of molecular discovery that we propose to formulate as a single shared task of conditional synthetic pathway generation. We report an amortized approach to generate synthetic pathways as a Markov decision process conditioned on a target molecular embedding. This approach allows us to conduct synthesis planning in a bottom-up manner and design synthesizable molecules by decoding from optimized conditional codes, demonstrating the potential to solve both problems of design and synthesis simultaneously. The approach leverages neural networks to probabilistically model the synthetic trees, one reaction step at a time, according to reactivity rules encoded in a discrete action space of reaction templates. We train these networks on hundreds of thousands of artificial pathways generated from a pool of purchasable compounds and a list of expert-curated templates. We validate our method with (a) the recovery of molecules using conditional generation, (b) the identification of synthesizable structural analogs, and (c) the optimization of molecular structures given oracle functions relevant to drug discovery.
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Current efficient fine-tuning methods (e.g., adapters, prefix-tuning, etc.) have optimized conditional text generation via training a small set of extra parameters of the neural language model, while freezing the rest for efficiency. While showing strong performance on some generation tasks, they don't generalize across all generation tasks. In this work, we show that prompt based conditional text generation can be improved with simple and efficient methods that simulate modeling the discourse structure of human written text. We introduce two key design choices: First we show that a higher-level discourse structure of human written text can be modelled with \textit{hierarchical blocking} on prefix parameters that enable spanning different parts of the input and output text and yield more coherent output generations. Second, we propose sparse prefix tuning by introducing \textit{attention sparsity} on the prefix parameters at different layers of the network and learn sparse transformations on the softmax-function, respectively. We find that sparse attention enables the prefix-tuning to better control of the input contents (salient facts) yielding more efficient tuning of the prefix-parameters. Experiments on a wide-variety of text generation tasks show that structured design of prefix parameters can achieve comparable results to fine-tuning all parameters while outperforming standard prefix-tuning on all generation tasks even in low-resource settings.
This paper deals with differentiable dynamical models congruent with neural process theories that cast brain function as the hierarchical refinement of an internal generative model explaining observations. Our work extends existing implementations of gradient-based predictive coding with automatic differentiation and allows to integrate deep neural networks for non-linear state parameterization. Gradient-based predictive coding optimises inferred states and weights locally in for each layer by optimising precision-weighted prediction errors that propagate from stimuli towards latent states. Predictions flow backwards, from latent states towards lower layers. The model suggested here optimises hierarchical and dynamical predictions of latent states. Hierarchical predictions encode expected content and hierarchical structure. Dynamical predictions capture changes in the encoded content along with higher order derivatives. Hierarchical and dynamical predictions interact and address different aspects of the same latent states. We apply the model to various perception and planning tasks on sequential data and show their mutual dependence. In particular, we demonstrate how learning sampling distances in parallel address meaningful locations data sampled at discrete time steps. We discuss possibilities to relax the assumption of linear hierarchies in favor of more flexible graph structure with emergent properties. We compare the granular structure of the model with canonical microcircuits describing predictive coding in biological networks and review the connection to Markov Blankets as a tool to characterize modularity. A final section sketches out ideas for efficient perception and planning in nested spatio-temporal hierarchies.
Deep clustering (DC) leverages the representation power of deep architectures to learn embedding spaces that are optimal for cluster analysis. This approach filters out low-level information irrelevant for clustering and has proven remarkably successful for high dimensional data spaces. Some DC methods employ Generative Adversarial Networks (GANs), motivated by the powerful latent representations these models are able to learn implicitly. In this work, we propose HC-MGAN, a new technique based on GANs with multiple generators (MGANs), which have not been explored for clustering. Our method is inspired by the observation that each generator of a MGAN tends to generate data that correlates with a sub-region of the real data distribution. We use this clustered generation to train a classifier for inferring from which generator a given image came from, thus providing a semantically meaningful clustering for the real distribution. Additionally, we design our method so that it is performed in a top-down hierarchical clustering tree, thus proposing the first hierarchical DC method, to the best of our knowledge. We conduct several experiments to evaluate the proposed method against recent DC methods, obtaining competitive results. Last, we perform an exploratory analysis of the hierarchical clustering tree that highlights how accurately it organizes the data in a hierarchy of semantically coherent patterns.
Efficiently discovering molecules that meet various property requirements can significantly benefit the drug discovery industry. Since it is infeasible to search over the entire chemical space, recent works adopt generative models for goal-directed molecular generation. They tend to utilize the iterative processes, optimizing the parameters of the molecular generative models at each iteration to produce promising molecules for further validation. Assessments are exploited to evaluate the generated molecules at each iteration, providing direction for model optimization. However, most previous works require a massive number of expensive and time-consuming assessments, e.g., wet experiments and molecular dynamic simulations, leading to the lack of practicability. To reduce the assessments in the iterative process, we propose a cost-effective evolution strategy in latent space, which optimizes the molecular latent representation vectors instead. We adopt a pre-trained molecular generative model to map the latent and observation spaces, taking advantage of the large-scale unlabeled molecules to learn chemical knowledge. To further reduce the number of expensive assessments, we introduce a pre-screener as the proxy to the assessments. We conduct extensive experiments on multiple optimization tasks comparing the proposed framework to several advanced techniques, showing that the proposed framework achieves better performance with fewer assessments.
Drug Discovery is a fundamental and ever-evolving field of research. The design of new candidate molecules requires large amounts of time and money, and computational methods are being increasingly employed to cut these costs. Machine learning methods are ideal for the design of large amounts of potential new candidate molecules, which are naturally represented as graphs. Graph generation is being revolutionized by deep learning methods, and molecular generation is one of its most promising applications. In this paper, we introduce a sequential molecular graph generator based on a set of graph neural network modules, which we call MG^2N^2. At each step, a node or a group of nodes is added to the graph, along with its connections. The modular architecture simplifies the training procedure, also allowing an independent retraining of a single module. Sequentiality and modularity make the generation process interpretable. The use of graph neural networks maximizes the information in input at each generative step, which consists of the subgraph produced during the previous steps. Experiments of unconditional generation on the QM9 and Zinc datasets show that our model is capable of generalizing molecular patterns seen during the training phase, without overfitting. The results indicate that our method is competitive, and outperforms challenging baselines for unconditional generation.
We present Neural A*, a novel data-driven search method for path planning problems. Despite the recent increasing attention to data-driven path planning, a machine learning approach to search-based planning is still challenging due to the discrete nature of search algorithms. In this work, we reformulate a canonical A* search algorithm to be differentiable and couple it with a convolutional encoder to form an end-to-end trainable neural network planner. Neural A* solves a path planning problem by encoding a problem instance to a guidance map and then performing the differentiable A* search with the guidance map. By learning to match the search results with ground-truth paths provided by experts, Neural A* can produce a path consistent with the ground truth accurately and efficiently. Our extensive experiments confirmed that Neural A* outperformed state-of-the-art data-driven planners in terms of the search optimality and efficiency trade-off, and furthermore, successfully predicted realistic human trajectories by directly performing search-based planning on natural image inputs.
Retrosynthetic planning is a critical task in organic chemistry which identifies a series of reactions that can lead to the synthesis of a target product. The vast number of possible chemical transformations makes the size of the search space very big, and retrosynthetic planning is challenging even for experienced chemists. However, existing methods either require expensive return estimation by rollout with high variance, or optimize for search speed rather than the quality. In this paper, we propose Retro*, a neural-based A*-like algorithm that finds high-quality synthetic routes efficiently. It maintains the search as an AND-OR tree, and learns a neural search bias with off-policy data. Then guided by this neural network, it performs best-first search efficiently during new planning episodes. Experiments on benchmark USPTO datasets show that, our proposed method outperforms existing state-of-the-art with respect to both the success rate and solution quality, while being more efficient at the same time.
Most conditional generation tasks expect diverse outputs given a single conditional context. However, conditional generative adversarial networks (cGANs) often focus on the prior conditional information and ignore the input noise vectors, which contribute to the output variations. Recent attempts to resolve the mode collapse issue for cGANs are usually task-specific and computationally expensive. In this work, we propose a simple yet effective regularization term to address the mode collapse issue for cGANs. The proposed method explicitly maximizes the ratio of the distance between generated images with respect to the corresponding latent codes, thus encouraging the generators to explore more minor modes during training. This mode seeking regularization term is readily applicable to various conditional generation tasks without imposing training overhead or modifying the original network structures. We validate the proposed algorithm on three conditional image synthesis tasks including categorical generation, image-to-image translation, and text-to-image synthesis with different baseline models. Both qualitative and quantitative results demonstrate the effectiveness of the proposed regularization method for improving diversity without loss of quality.
Conventional neural autoregressive decoding commonly assumes a fixed left-to-right generation order, which may be sub-optimal. In this work, we propose a novel decoding algorithm -- InDIGO -- which supports flexible sequence generation in arbitrary orders through insertion operations. We extend Transformer, a state-of-the-art sequence generation model, to efficiently implement the proposed approach, enabling it to be trained with either a pre-defined generation order or adaptive orders obtained from beam-search. Experiments on four real-world tasks, including word order recovery, machine translation, image caption and code generation, demonstrate that our algorithm can generate sequences following arbitrary orders, while achieving competitive or even better performance compared to the conventional left-to-right generation. The generated sequences show that InDIGO adopts adaptive generation orders based on input information.
Generative Adversarial networks (GANs) have obtained remarkable success in many unsupervised learning tasks and unarguably, clustering is an important unsupervised learning problem. While one can potentially exploit the latent-space back-projection in GANs to cluster, we demonstrate that the cluster structure is not retained in the GAN latent space. In this paper, we propose ClusterGAN as a new mechanism for clustering using GANs. By sampling latent variables from a mixture of one-hot encoded variables and continuous latent variables, coupled with an inverse network (which projects the data to the latent space) trained jointly with a clustering specific loss, we are able to achieve clustering in the latent space. Our results show a remarkable phenomenon that GANs can preserve latent space interpolation across categories, even though the discriminator is never exposed to such vectors. We compare our results with various clustering baselines and demonstrate superior performance on both synthetic and real datasets.
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