GDiffRetro: Retrosynthesis Prediction with Dual Graph Enhanced Molecular Representation and Diffusion Generation

Retrosynthesis prediction focuses on identifying reactants capable of synthesizing a target product. Typically, the retrosynthesis prediction involves two phases: Reaction Center Identification and Reactant Generation. However, we argue that most existing methods suffer from two limitations in the two phases: (i) Existing models do not adequately capture the ``face'' information in molecular graphs for the reaction center identification. (ii) Current approaches for the reactant generation predominantly use sequence generation in a 2D space, which lacks versatility in generating reasonable distributions for completed reactive groups and overlooks molecules' inherent 3D properties. To overcome the above limitations, we propose GDiffRetro. For the reaction center identification, GDiffRetro uniquely integrates the original graph with its corresponding dual graph to represent molecular structures, which helps guide the model to focus more on the faces in the graph. For the reactant generation, GDiffRetro employs a conditional diffusion model in 3D to further transform the obtained synthon into a complete reactant. Our experimental findings reveal that GDiffRetro outperforms state-of-the-art semi-template models across various evaluative metrics.

Are High-Degree Representations Really Unnecessary in Equivariant Graph Neural Networks?

Equivariant Graph Neural Networks (GNNs) that incorporate E(3) symmetry have achieved significant success in various scientific applications. As one of the most successful models, EGNN leverages a simple scalarization technique to perform equivariant message passing over only Cartesian vectors (i.e., 1st-degree steerable vectors), enjoying greater efficiency and efficacy compared to equivariant GNNs using higher-degree steerable vectors. This success suggests that higher-degree representations might be unnecessary. In this paper, we disprove this hypothesis by exploring the expressivity of equivariant GNNs on symmetric structures, including $k$-fold rotations and regular polyhedra. We theoretically demonstrate that equivariant GNNs will always degenerate to a zero function if the degree of the output representations is fixed to 1 or other specific values. Based on this theoretical insight, we propose HEGNN, a high-degree version of EGNN to increase the expressivity by incorporating high-degree steerable vectors while maintaining EGNN's efficiency through the scalarization trick. Our extensive experiments demonstrate that HEGNN not only aligns with our theoretical analyses on toy datasets consisting of symmetric structures, but also shows substantial improvements on more complicated datasets such as $N$-body and MD17. Our theoretical findings and empirical results potentially open up new possibilities for the research of equivariant GNNs.

Molecular Graph Representation Learning Integrating Large Language Models with Domain-specific Small Models

Molecular property prediction is a crucial foundation for drug discovery. In recent years, pre-trained deep learning models have been widely applied to this task. Some approaches that incorporate prior biological domain knowledge into the pre-training framework have achieved impressive results. However, these methods heavily rely on biochemical experts, and retrieving and summarizing vast amounts of domain knowledge literature is both time-consuming and expensive. Large Language Models (LLMs) have demonstrated remarkable performance in understanding and efficiently providing general knowledge. Nevertheless, they occasionally exhibit hallucinations and lack precision in generating domain-specific knowledge. Conversely, Domain-specific Small Models (DSMs) possess rich domain knowledge and can accurately calculate molecular domain-related metrics. However, due to their limited model size and singular functionality, they lack the breadth of knowledge necessary for comprehensive representation learning. To leverage the advantages of both approaches in molecular property prediction, we propose a novel Molecular Graph representation learning framework that integrates Large language models and Domain-specific small models (MolGraph-LarDo). Technically, we design a two-stage prompt strategy where DSMs are introduced to calibrate the knowledge provided by LLMs, enhancing the accuracy of domain-specific information and thus enabling LLMs to generate more precise textual descriptions for molecular samples. Subsequently, we employ a multi-modal alignment method to coordinate various modalities, including molecular graphs and their corresponding descriptive texts, to guide the pre-training of molecular representations. Extensive experiments demonstrate the effectiveness of the proposed method.

Characterizing the Influence of Topology on Graph Learning Tasks

Graph neural networks (GNN) have achieved remarkable success in a wide range of tasks by encoding features combined with topology to create effective representations. However, the fundamental problem of understanding and analyzing how graph topology influences the performance of learning models on downstream tasks has not yet been well understood. In this paper, we propose a metric, TopoInf, which characterizes the influence of graph topology by measuring the level of compatibility between the topological information of graph data and downstream task objectives. We provide analysis based on the decoupled GNNs on the contextual stochastic block model to demonstrate the effectiveness of the metric. Through extensive experiments, we demonstrate that TopoInf is an effective metric for measuring topological influence on corresponding tasks and can be further leveraged to enhance graph learning.

Sculpting Molecules in 3D: A Flexible Substructure Aware Framework for Text-Oriented Molecular Optimization

The integration of deep learning, particularly AI-Generated Content, with high-quality data derived from ab initio calculations has emerged as a promising avenue for transforming the landscape of scientific research. However, the challenge of designing molecular drugs or materials that incorporate multi-modality prior knowledge remains a critical and complex undertaking. Specifically, achieving a practical molecular design necessitates not only meeting the diversity requirements but also addressing structural and textural constraints with various symmetries outlined by domain experts. In this article, we present an innovative approach to tackle this inverse design problem by formulating it as a multi-modality guidance generation/optimization task. Our proposed solution involves a textural-structure alignment symmetric diffusion framework for the implementation of molecular generation/optimization tasks, namely 3DToMolo. 3DToMolo aims to harmonize diverse modalities, aligning them seamlessly to produce molecular structures adhere to specified symmetric structural and textural constraints by experts in the field. Experimental trials across three guidance generation settings have shown a superior hit generation performance compared to state-of-the-art methodologies. Moreover, 3DToMolo demonstrates the capability to generate novel molecules, incorporating specified target substructures, without the need for prior knowledge. This work not only holds general significance for the advancement of deep learning methodologies but also paves the way for a transformative shift in molecular design strategies. 3DToMolo creates opportunities for a more nuanced and effective exploration of the vast chemical space, opening new frontiers in the development of molecular entities with tailored properties and functionalities.

MoD-SLAM: Monocular Dense Mapping for Unbounded 3D Scene Reconstruction

Neural implicit representations have recently been demonstrated in many fields including Simultaneous Localization And Mapping (SLAM). Current neural SLAM can achieve ideal results in reconstructing bounded scenes, but this relies on the input of RGB-D images. Neural-based SLAM based only on RGB images is unable to reconstruct the scale of the scene accurately, and it also suffers from scale drift due to errors accumulated during tracking. To overcome these limitations, we present MoD-SLAM, a monocular dense mapping method that allows global pose optimization and 3D reconstruction in real-time in unbounded scenes. Optimizing scene reconstruction by monocular depth estimation and using loop closure detection to update camera pose enable detailed and precise reconstruction on large scenes. Compared to previous work, our approach is more robust, scalable and versatile. Our experiments demonstrate that MoD-SLAM has more excellent mapping performance than prior neural SLAM methods, especially in large borderless scenes.

Large Language Models as Topological Structure Enhancers for Text-Attributed Graphs

The latest advancements in large language models (LLMs) have revolutionized the field of natural language processing (NLP). Inspired by the success of LLMs in NLP tasks, some recent work has begun investigating the potential of applying LLMs in graph learning tasks. However, most of the existing work focuses on utilizing LLMs as powerful node feature augmenters, leaving employing LLMs to enhance graph topological structures an understudied problem. In this work, we explore how to leverage the information retrieval and text generation capabilities of LLMs to refine/enhance the topological structure of text-attributed graphs (TAGs) under the node classification setting. First, we propose using LLMs to help remove unreliable edges and add reliable ones in the TAG. Specifically, we first let the LLM output the semantic similarity between node attributes through delicate prompt designs, and then perform edge deletion and edge addition based on the similarity. Second, we propose using pseudo-labels generated by the LLM to improve graph topology, that is, we introduce the pseudo-label propagation as a regularization to guide the graph neural network (GNN) in learning proper edge weights. Finally, we incorporate the two aforementioned LLM-based methods for graph topological refinement into the process of GNN training, and perform extensive experiments on four real-world datasets. The experimental results demonstrate the effectiveness of LLM-based graph topology refinement (achieving a 0.15%--2.47% performance gain on public benchmarks).

Empower Text-Attributed Graphs Learning with Large Language Models (LLMs)

Text-attributed graphs have recently garnered significant attention due to their wide range of applications in web domains. Existing methodologies employ word embedding models for acquiring text representations as node features, which are subsequently fed into Graph Neural Networks (GNNs) for training. Recently, the advent of Large Language Models (LLMs) has introduced their powerful capabilities in information retrieval and text generation, which can greatly enhance the text attributes of graph data. Furthermore, the acquisition and labeling of extensive datasets are both costly and time-consuming endeavors. Consequently, few-shot learning has emerged as a crucial problem in the context of graph learning tasks. In order to tackle this challenge, we propose a lightweight paradigm called ENG, which adopts a plug-and-play approach to empower text-attributed graphs through node generation using LLMs. Specifically, we utilize LLMs to extract semantic information from the labels and generate samples that belong to these categories as exemplars. Subsequently, we employ an edge predictor to capture the structural information inherent in the raw dataset and integrate the newly generated samples into the original graph. This approach harnesses LLMs for enhancing class-level information and seamlessly introduces labeled nodes and edges without modifying the raw dataset, thereby facilitating the node classification task in few-shot scenarios. Extensive experiments demonstrate the outstanding performance of our proposed paradigm, particularly in low-shot scenarios. For instance, in the 1-shot setting of the ogbn-arxiv dataset, ENG achieves a 76% improvement over the baseline model.

Measuring and Sampling: A Metric-guided Subgraph Learning Framework for Graph Neural Network

Graph neural network (GNN) has shown convincing performance in learning powerful node representations that preserve both node attributes and graph structural information. However, many GNNs encounter problems in effectiveness and efficiency when they are designed with a deeper network structure or handle large-sized graphs. Several sampling algorithms have been proposed for improving and accelerating the training of GNNs, yet they ignore understanding the source of GNN performance gain. The measurement of information within graph data can help the sampling algorithms to keep high-value information while removing redundant information and even noise. In this paper, we propose a Metric-Guided (MeGuide) subgraph learning framework for GNNs. MeGuide employs two novel metrics: Feature Smoothness and Connection Failure Distance to guide the subgraph sampling and mini-batch based training. Feature Smoothness is designed for analyzing the feature of nodes in order to retain the most valuable information, while Connection Failure Distance can measure the structural information to control the size of subgraphs. We demonstrate the effectiveness and efficiency of MeGuide in training various GNNs on multiple datasets.

Collaborative Graph Contrastive Learning: Data Augmentation Composition May Not be Necessary for Graph Representation Learning

Unsupervised graph representation learning is a non-trivial topic for graph data. The success of contrastive learning and self-supervised learning in the unsupervised representation learning of structured data inspires similar attempts on the graph. The current unsupervised graph representation learning and pre-training using the contrastive loss are mainly based on the contrast between handcrafted augmented graph data. However, the graph data augmentation is still not well-explored due to the unpredictable invariance. In this paper, we propose a novel collaborative graph neural networks contrastive learning framework (CGCL), which uses multiple graph encoders to observe the graph. Features observed from different views act as the graph augmentation for contrastive learning between graph encoders, avoiding any perturbation to guarantee the invariance. CGCL is capable of handling both graph-level and node-level representation learning. Extensive experiments demonstrate the advantages of CGCL in unsupervised graph representation learning and the non-necessity of handcrafted data augmentation composition for graph representation learning.