skip to main content

This content will become publicly available on May 1, 2024

Title: Retrieval-based Controllable Molecule Generation
Generating new molecules with specified chemical and biological properties via generative models has emerged as a promising direction for drug discovery. However, existing methods require extensive training/fine-tuning with a large dataset, often unavailable in real-world generation tasks. In this work, we propose a new retrieval-based framework for controllable molecule generation. We use a small set of exemplar molecules, i.e., those that (partially) satisfy the design criteria, to steer the pre-trained generative model towards synthesizing molecules that satisfy the given design criteria. We design a retrieval mechanism that retrieves and fuses the exemplar molecules with the input molecule, which is trained by a new self-supervised objective that predicts the nearest neighbor of the input molecule. We also propose an iterative refinement process to dynamically update the generated molecules and retrieval database for better generalization. Our approach is agnostic to the choice of generative models and requires no task-specific fine-tuning. On various tasks ranging from simple design criteria to a challenging real-world scenario for designing lead compounds that bind to the SARS-CoV-2 main protease, we demonstrate our approach extrapolates well beyond the retrieval database, and achieves better performance and wider applicability than previous methods.  more » « less
Award ID(s):
1911094 1838177 1730574
Author(s) / Creator(s):
; ; ; ; ;
Date Published:
Journal Name:
International Conference on Learning Representations (ICLR) 2023
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Transfer learning using ImageNet pre-trained models has been the de facto approach in a wide range of computer vision tasks. However, fine-tuning still requires task-specific training data. In this paper, we propose N3 (Neural Networks from Natural Language) - a new paradigm of synthesizing task-specific neural networks from language descriptions and a generic pre-trained model. N3 leverages language descriptions to generate parameter adaptations as well as a new task-specific classification layer for a pre-trained neural network, effectively “fine-tuning” the network for a new task using only language descriptions as input. To the best of our knowledge, N3 is the first method to synthesize entire neural networks from natural language. Experimental results show that N3 can out-perform previous natural-language based zero-shot learning methods across 4 different zero-shot image classification benchmarks. We also demonstrate a simple method to help identify keywords in language descriptions leveraged by N3 when synthesizing model parameters. 
    more » « less
  2. Machine learning (ML) accelerates the exploration of material properties and their links to the structure of the underlying molecules. In previous work [Shi et al. ACS Applied Materials & Interfaces 2022, 14, 37161−37169.], ML models were applied to predict the adhesive free energy of polymer–surface interactions with high accuracy from the knowledge of the sequence data, demonstrating successes in inverse-design of polymer sequence for known surface compositions. While the method was shown to be successful in designing polymers for a known surface, extensive data sets were needed for each specific surface in order to train the surrogate models. Ideally, one should be able to infer information about similar surfaces without having to regenerate a full complement of adhesion data for each new case. In the current work, we demonstrate a transfer learning (TL) technique using a deep neural network to improve the accuracy of ML models trained on small data sets by pretraining on a larger database from a related system and fine-tuning the weights of all layers with a small amount of additional data. The shared knowledge from the pretrained model facilitates the prediction accuracy significantly on small data sets. We also explore the limits of database size on accuracy and the optimal tuning of network architecture and parameters for our learning tasks. While applied to a relatively simple coarse-grained (CG) polymer model, the general lessons of this study apply to detailed modeling studies and the broader problems of inverse materials design. 
    more » « less
  3. Transfer learning has fundamentally changed the landscape of natural language processing (NLP). Many state-of-the-art models are first pre-trained on a large text corpus and then fine-tuned on downstream tasks. However, due to limited data resources from downstream tasks and the extremely high complexity of pre-trained models, aggressive fine-tuning of- ten causes the fine-tuned model to overfit the training data of downstream tasks and fail to generalize to unseen data. To address such an issue in a principled manner, we propose a new learning framework for robust and efficient fine-tuning for pre-trained models to attain better generalization performance. The pro- posed framework contains two important in- gredients: 1. Smoothness-inducing regulariza- tion, which effectively manages the complex- ity of the model; 2. Bregman proximal point optimization, which is an instance of trust- region methods and can prevent aggressive up- dating. Our experiments show that the pro- posed framework achieves new state-of-the-art performance on a number of NLP tasks includ- ing GLUE, SNLI, SciTail and ANLI. More- over, it also outperforms the state-of-the-art T5 model, which is the largest pre-trained model containing 11 billion parameters, on GLUE. 
    more » « less
  4. Real-world applications often involve irregular time series, for which the time intervals between successive observations are non-uniform. Irregularity across multiple features in a multi-variate time series further results in a different subset of features at any given time (i.e., asynchronicity). Existing pre-training schemes for time-series, however, often assume regularity of time series and make no special treatment of irregularity. We argue that such irregularity offers insight about domain property of the data—for example, frequency of hospital visits may signal patient health condition—that can guide representation learning. In this work, we propose PrimeNet to learn a self-supervised representation for irregular multivariate time-series. Specifically, we design a timesensitive contrastive learning and data reconstruction task to pre-train a model. Irregular time-series exhibits considerable variations in sampling density over time. Hence, our triplet generation strategy follows the density of the original data points, preserving its native irregularity. Moreover, the sampling density variation over time makes data reconstruction difficult for different regions. Therefore, we design a data masking technique that always masks a constant time duration to accommodate reconstruction for regions of different sampling density. We learn with these tasks using unlabeled data to build a pre-trained model and fine-tune on a downstream task with limited labeled data, in contrast with existing fully supervised approach for irregular time-series, requiring large amounts of labeled data. Experiment results show that PrimeNet significantly outperforms state-of-the-art methods on naturally irregular and asynchronous data from Healthcare and IoT applications for several downstream tasks, including classification, interpolation, and regression. 
    more » « less
  5. ABSTRACT Astronomers have typically set out to solve supervised machine learning problems by creating their own representations from scratch. We show that deep learning models trained to answer every Galaxy Zoo DECaLS question learn meaningful semantic representations of galaxies that are useful for new tasks on which the models were never trained. We exploit these representations to outperform several recent approaches at practical tasks crucial for investigating large galaxy samples. The first task is identifying galaxies of similar morphology to a query galaxy. Given a single galaxy assigned a free text tag by humans (e.g. ‘#diffuse’), we can find galaxies matching that tag for most tags. The second task is identifying the most interesting anomalies to a particular researcher. Our approach is 100 per cent accurate at identifying the most interesting 100 anomalies (as judged by Galaxy Zoo 2 volunteers). The third task is adapting a model to solve a new task using only a small number of newly labelled galaxies. Models fine-tuned from our representation are better able to identify ring galaxies than models fine-tuned from terrestrial images (ImageNet) or trained from scratch. We solve each task with very few new labels; either one (for the similarity search) or several hundred (for anomaly detection or fine-tuning). This challenges the longstanding view that deep supervised methods require new large labelled data sets for practical use in astronomy. To help the community benefit from our pretrained models, we release our fine-tuning code zoobot. Zoobot is accessible to researchers with no prior experience in deep learning. 
    more » « less