skip to main content

Explore Research Products in the NSF-PAR

Title: Molecular Graph Generation via Geometric Scattering
Graph neural networks (GNNs) have been used extensively for addressing problems in drug design and discovery. Both ligand and target molecules are represented as graphs with node and edge features encoding information about atomic elements and bonds respectively. Although existing deep learning models perform remarkably well at predicting physicochemical properties and binding affinities, the generation of new molecules with optimized properties remains challenging. Inherently, most GNNs perform poorly in whole-graph representation due to the limitations of the message-passing paradigm. Furthermore, step-by-step graph generation frameworks that use reinforcement learning or other sequential processing can be slow and result in a high proportion of invalid molecules with substantial post-processing needed in order to satisfy the principles of stoichiometry. To address these issues, we propose a representation-first approach to molecular graph generation. We guide the latent representation of an autoencoder by capturing graph structure information with the geometric scattering transform and apply penalties that structure the representation also by molecular properties. We show that this highly structured latent space can be directly used for molecular graph generation by the use of a GAN. We demonstrate that our architecture learns meaningful representations of drug datasets and provides a platform for goal-directed drug synthesis.  more » « less
Award ID(s):
2047856
NSF-PAR ID:
10352684
Author(s) / Creator(s):
Date Published:
Journal Name:
IEEE Machine Learning for Signal Processing
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. ; ; ; ; ; ( , Bioinformatics)
    Abstract Motivation

    Expanding our knowledge of small molecules beyond what is known in nature or designed in wet laboratories promises to significantly advance cheminformatics, drug discovery, biotechnology and material science. In silico molecular design remains challenging, primarily due to the complexity of the chemical space and the non-trivial relationship between chemical structures and biological properties. Deep generative models that learn directly from data are intriguing, but they have yet to demonstrate interpretability in the learned representation, so we can learn more about the relationship between the chemical and biological space. In this article, we advance research on disentangled representation learning for small molecule generation. We build on recent work by us and others on deep graph generative frameworks, which capture atomic interactions via a graph-based representation of a small molecule. The methodological novelty is how we leverage the concept of disentanglement in the graph variational autoencoder framework both to generate biologically relevant small molecules and to enhance model interpretability.

     Results

    Extensive qualitative and quantitative experimental evaluation in comparison with state-of-the-art models demonstrate the superiority of our disentanglement framework. We believe this work is an important step to address key challenges in small molecule generation with deep generative frameworks.

     Availability and implementation

    Training and generated data are made available at https://ieee-dataport.org/documents/dataset-disentangled-representation-learning-interpretable-molecule-generation. All code is made available at https://anonymous.4open.science/r/D-MolVAE-2799/.

     Supplementary information

    Supplementary data are available at Bioinformatics online.

     
    more » « less
  2. ; ; ( , The Journal of Chemical Physics)

    Bottom-up methods for coarse-grained (CG) molecular modeling are critically needed to establish rigorous links between atomistic reference data and reduced molecular representations. For a target molecule, the ideal reduced CG representation is a function of both the conformational ensemble of the system and the target physical observable(s) to be reproduced at the CG resolution. However, there is an absence of algorithms for selecting CG representations of molecules from which complex properties, including molecular electronic structure, can be accurately modeled. We introduce continuously gated message passing (CGMP), a graph neural network (GNN) method for atomically decomposing molecular electronic structure sampled over conformational ensembles. CGMP integrates 3D-invariant GNNs and a novel gated message passing system to continuously reduce the atomic degrees of freedom accessible for electronic predictions, resulting in a one-shot importance ranking of atoms contributing to a target molecular property. Moreover, CGMP provides the first approach by which to quantify the degeneracy of “good” CG representations conditioned on specific prediction targets, facilitating the development of more transferable CG representations. We further show how CGMP can be used to highlight multiatom correlations, illuminating a path to developing CG electronic Hamiltonians in terms of interpretable collective variables for arbitrarily complex molecules.

     
    more » « less
  3. ; ; ; ; ; ; ( , 2021 IEEE International Conference on Bioinformatics and Biomedicine (BIBM))
    Representation learning via deep generative models is opening a new avenue for small molecule generation in silico. Linking chemical and biological space remains a key challenge. In this paper, we debut a graph-based variational autoencoder framework to address this challenge under the umbrella of disentangled representation learning. The framework permits several inductive biases that connect the learned latent factors to molecular properties. Evaluation on diverse benchmark datasets shows that the resulting models are powerful and open up an exciting line of research on controllable molecule generation in support of cheminformatics, drug discovery, and other application settings. 
    more » « less
  4. ; ; ; ; ; ; ; ; ( , Bioinformatics)
    Abstract Motivation

    The crux of molecular property prediction is to generate meaningful representations of the molecules. One promising route is to exploit the molecular graph structure through graph neural networks (GNNs). Both atoms and bonds significantly affect the chemical properties of a molecule, so an expressive model ought to exploit both node (atom) and edge (bond) information simultaneously. Inspired by this observation, we explore the multi-view modeling with GNN (MVGNN) to form a novel paralleled framework, which considers both atoms and bonds equally important when learning molecular representations. In specific, one view is atom-central and the other view is bond-central, then the two views are circulated via specifically designed components to enable more accurate predictions. To further enhance the expressive power of MVGNN, we propose a cross-dependent message-passing scheme to enhance information communication of different views. The overall framework is termed as CD-MVGNN.

     Results

    We theoretically justify the expressiveness of the proposed model in terms of distinguishing non-isomorphism graphs. Extensive experiments demonstrate that CD-MVGNN achieves remarkably superior performance over the state-of-the-art models on various challenging benchmarks. Meanwhile, visualization results of the node importance are consistent with prior knowledge, which confirms the interpretability power of CD-MVGNN.

     Availability and implementation

    The code and data underlying this work are available in GitHub at https://github.com/uta-smile/CD-MVGNN.

     Supplementary information

    Supplementary data are available at Bioinformatics online.

     
    more » « less
  5. ; ; ; ; ( , Scientific Reports)
    null (Ed.)
    Abstract Molecular interaction networks are powerful resources for molecular discovery. They are increasingly used with machine learning methods to predict biologically meaningful interactions. While deep learning on graphs has dramatically advanced the prediction prowess, current graph neural network (GNN) methods are mainly optimized for prediction on the basis of direct similarity between interacting nodes. In biological networks, however, similarity between nodes that do not directly interact has proved incredibly useful in the last decade across a variety of interaction networks. Here, we present SkipGNN, a graph neural network approach for the prediction of molecular interactions. SkipGNN predicts molecular interactions by not only aggregating information from direct interactions but also from second-order interactions, which we call skip similarity. In contrast to existing GNNs, SkipGNN receives neural messages from two-hop neighbors as well as immediate neighbors in the interaction network and non-linearly transforms the messages to obtain useful information for prediction. To inject skip similarity into a GNN, we construct a modified version of the original network, called the skip graph. We then develop an iterative fusion scheme that optimizes a GNN using both the skip graph and the original graph. Experiments on four interaction networks, including drug–drug, drug–target, protein–protein, and gene–disease interactions, show that SkipGNN achieves superior and robust performance. Furthermore, we show that unlike popular GNNs, SkipGNN learns biologically meaningful embeddings and performs especially well on noisy, incomplete interaction networks. 
    more » « less
  • Citation Formats
  • MLA
  • APA
  • Chicago
  • BibTeX
  • Save / Share this Record
  • Send to Email