Interaction-Based Inductive Bias in Graph Neural Networks: Enhancing Protein-Ligand Binding Affinity Predictions From 3D Structures.

Aspect-based sentiment analysis aims to predict sentiment polarities of given aspects in text. Most current approaches employ attention-based neural methods to capture semantic relationships between aspects and words in one sentence. However, these methods ignore the fact that sentences with the same aspect and sentiment polarity often share the structure and semantic information in a domain, which leads to lower model performance. To mitigate this problem, we propose a heterogeneous aspect graph neural network (HAGNN) to learn the structure and semantic knowledge from intersentence relationships. Our model is a heterogeneous graph neural network since it contains three different kinds of nodes: word nodes, aspect nodes, and sentence nodes. These nodes can pass structure and semantic information between each other and update their embeddings to improve the performance of our model. To the best of our knowledge, we are the first to use a heterogeneous graph to capture relationships between sentences and aspects. The experimental results on five public datasets show the effectiveness of our model outperforming some state-of-the-art models.

Predicting the next interaction of a short-term interaction session is a challenging task in session-based recommendation. Almost all existing works rely on item transition patterns, and neglect the impact of user historical sessions while modeling user preference, which often leads to non-personalized recommendation. Additionally, existing personalized session-based recommenders capture user preference only based on the sessions of the current user, but ignore the useful item-transition patterns from other user's historical sessions. To address these issues, we propose a novel Heterogeneous Global Graph Neural Networks (HG-GNN) to exploit the item transitions over all sessions in a subtle manner for better inferring user preference from the current and historical sessions. To effectively exploit the item transitions over all sessions from users, we propose a novel heterogeneous global graph that contains item transitions of sessions, user-item interactions and global co-occurrence items. Moreover, to capture user preference from sessions comprehensively, we propose to learn two levels of user representations from the global graph via two graph augmented preference encoders. Specifically, we design a novel heterogeneous graph neural network (HGNN) on the heterogeneous global graph to learn the long-term user preference and item representations with rich semantics. Based on the HGNN, we propose the Current Preference Encoder and the Historical Preference Encoder to capture the different levels of user preference from the current and historical sessions, respectively. To achieve personalized recommendation, we integrate the representations of the user current preference and historical interests to generate the final user preference representation. Extensive experimental results on three real-world datasets show that our model outperforms other state-of-the-art methods.

In the drug discovery process and repurposing of existing drugs, accurately identifying ligands with high binding affinity to proteins is a very critical step. However, it sinks a lot of time and resources to detect the protein-ligand binding affinity through biological experiments. Therefore, it is very necessary to develop an accurate and reliable computational method to predict the binding affinity between protein and ligand. At present, some computational methods have been proposed to predict the protein-ligand binding affinity, but the absence of protein-ligand complexes structures restricts some predictive methods that require input the complexes structures. In this paper, a novel deep-learning-based method is proposed, named DPLA, to predict binding affinity by integrating multilevel information of protein and ligand. More specifically, our model extracted some important information, such as sequence representation, structural property representation of amino acids in protein and protein binding pocket, MACCS key ligand molecular fingerprint and ligand molecular network features. This method was tested on the PDBbind core set, and we compared it with some recent state-of-art protein-ligand affinity prediction methods. The excellent performance shows that DPLA is an accurate and reliable method for affinity prediction.

PLAGCA: Predicting protein-ligand binding affinity with the graph cross-attention mechanism.

Protein-ligand interactions are the molecular basis of many important cellular activities, such as gene regulation, cell metabolism, and signal transduction. Protein-ligand binding affinity is a crucial metric of the strength of the interaction between the two, and accurate prediction of its binding affinity is essential for discovering drugs' new uses. So far, although many predictive models based on machine learning and deep learning have been reported, most of the models mainly focus on one-dimensional sequence and two-dimensional structural characteristics of proteins and ligands, but fail to deeply explore the detailed interaction information between proteins and ligand atoms in the binding pocket region of three-dimensional space. In this study, we introduced a novel 4D tensor feature to capture key interactions within the binding pocket and developed a three-dimensional convolutional neural network (CNN) model based on this feature. Using ten-fold cross-validation, we identified the optimal parameter combination and pocket size. Additionally, we employed feature engineering to extract features across multiple dimensions, including one-dimensional sequences, two-dimensional structures of the ligand and protein, and three-dimensional interaction features between them. We proposed an efficient protein-ligand binding affinity prediction model MCDTA (multi-dimensional convolutional drug-target affinity), built on a multi-dimensional convolutional neural network framework. Feature ablation experiments revealed that the 4D tensor feature had the most significant impact on model performance. MCDTA performed exceptionally well on the PDBbind v.2020 dataset, achieving an RMSE of 1.231 and a PCC of 0.823. In comparative experiments, it outperformed five other mainstream binding affinity prediction models, with an RMSE of 1.349 and a PCC of 0.795. Moreover, MCDTA demonstrated strong generalization ability and practical screening performance across multiple benchmark datasets, highlighting its reliability and accuracy in predicting protein-ligand binding affinity. The code for MCDTA is available at https://github.com/dfhuang-AI/MCDTA .

Predicting protein-ligand binding affinity is a central issue in drug design. Various deep learning models have been published in recent years, where many of them rely on 3D protein-ligand complex structures as input and tend to focus on the single task of reproducing binding affinity. In this study, we have developed a graph neural network model called PLANET (Protein-Ligand Affinity prediction NETwork). This model takes the graph-represented 3D structure of the binding pocket on the target protein and the 2D chemical structure of the ligand molecule as input. It was trained through a multi-objective process with three related tasks, including deriving the protein-ligand binding affinity, protein-ligand contact map, and ligand distance matrix. Besides the protein-ligand complexes with known binding affinity data retrieved from the PDBbind database, a large number of non-binder decoys were also added to the training data for deriving the final model of PLANET. When tested on the CASF-2016 benchmark, PLANET exhibited a scoring power comparable to the best result yielded by other deep learning models as well as a reasonable ranking power and docking power. In virtual screening trials conducted on the DUD-E benchmark, PLANET's performance was notably better than several deep learning and machine learning models. As on the LIT-PCBA benchmark, PLANET achieved comparable accuracy as the conventional docking program Glide, but it only spent less than 1% of Glide's computation time to finish the same job because PLANET did not need exhaustive conformational sampling. Considering the decent accuracy and efficiency of PLANET in binding affinity prediction, it may become a useful tool for conducting large-scale virtual screening.

Accurate prediction of protein-ligand binding affinity is pivotal for drug design and discovery. Here, we proposed a novel deep fusion graph neural networks framework named FGNN to learn the protein-ligand interactions from the 3D structures of protein-ligand complexes. Unlike 1D sequences for proteins or 2D graphs for ligands, the 3D graph of protein-ligand complex enables the more accurate representations of the protein-ligand interactions. Benchmark studies have shown that our fusion models FGNN can achieve more accurate prediction of binding affinity than any individual algorithm. The advantages of fusion strategies have been demonstrated in terms of expressive power of data, learning efficiency and model interpretability. Our fusion models show satisfactory performances on diverse data sets, demonstrating their generalization ability. Given the good performances in both binding affinity prediction and virtual screening, our fusion models are expected to be practically applied for drug screening and design. Our work highlights the potential of the fusion graph neural network algorithm in solving complex prediction problems in computational biology and chemistry. The fusion graph neural networks (FGNN) model is freely available in https://github.com/LinaDongXMU/FGNN.

Heterogeneous graphs are an essential structure that models real-world data through different types of nodes and relationships between them, including multimodality, which comprises different types of data such as text, image, and audio. Graph Neural Networks (GNNs) are a prominent graph representation learning method that takes advantage of the graph structure and its attributes that, when applied to the multimodal heterogeneous graph, learn a unique semantic space for the different modalities. Consequently, it allows multimodal fusion through simple operators such as sum, average, or multiplication, generating unified representations considering the supplementary and complementarity relationships between the modalities. In multimodal heterogeneous graphs, the labeling process tends to be even more costly due to the multiple modalities analyzed, in addition to the imbalance of classes inherent to some applications. In order to overcome these problems in applications that comprise a class of interest, One-Class Learning (OCL) is used. Given the lack of studies on multimodal early fusion in heterogeneous graphs for OCL tasks, we proposed a method based on unsupervised GNN for heterogeneous graphs and evaluated different early fusion operators. In this paper, we extend another work by evaluating the behavior of the main GNN convolutions in the method. We highlight that using operators such as average, addition, and subtraction were the best early fusion operators. In addition, GNN layers that do not use an attention mechanism performed better. In this way, we argue for heterogeneous graph neural networks in multimodal using early fusion simple operators instead of well-often-used concatenation and less complex convolutions.

Heterogeneous Graph Neural Networks (GNNs) have shown good performance as a robust deep learning-based graph representation technique and have gained much research interest. Although it has adequately taken into account networks with a number of links and nodes, heterogeneity and the volume of semantic data provide significant obstacles. The attention mechanism, having great potential in a variety of areas, is one of the most interesting new developments in deep learning. This research demonstrates a system with two crucial attributes for embedding users and movies. The proposed framework achieves multi-level semantic attention using GNNs. We incorporated IMDB and Netflix Movie and TV Show datasets and merged them into a single consolidated dataset that was further utilized for results analysis. This paper mainly contributes a technique for movie recommendation using heterogeneous graphs and multi-level Semitics. We have proposed a framework that incorporates viewer and Director as an entity. During the research, we also combined two datasets in accordance with the proposed framework. After that, we evaluated the performance of the graph neural network on the heterogeneous graph. We discovered that the proposed model outperformed the current methodologies while using the proposed technique. Our model multilevel-Semitics-based framework shows effective results.

- Heterogeneous graph learning has emerged as a powerful paradigm for modeling complex relational data involving multiple types of nodes and edges. Unlike homogeneous graphs, heterogeneous graphs capture rich semantic relationships across diverse entities, enabling more expressive representations. This paper presents a comprehensive and structured review of heterogeneous graph learning, covering foundational theories, classical approaches, heterogeneous graph neural networks (HGNNs), and transformer-based architectures. Recent advances from 2020 to 2025, including multimodal, dynamic, and contrastive learning frameworks, are also discussed. Furthermore, we analyze experimental benchmarks, applications across domains, and key challenges such as scalability and interpretability. Finally, future research directions are outlined to guide advancements in this rapidly evolving field. Key Words: heterogeneous graphs, graph neural networks, HGNN, graph transformers, representation learning, knowledge graphs, deep learning

Heterogeneous Graph Neural Networks (HGNNs) have demonstrated remarkable capabilities in capturing effective information in heterogeneous graphs, achieving outstanding performance in various learning tasks. However, the heavy dependency of HGNNs on neighbors information may result in high latency, which restricts their practicality in real-world applications. Recent studies have attempted to overcome such latency in Graph Neural Networks (GNNs) by distilling knowledge into student models that do not rely on graph structure. But these approaches primarily focus on replicating teachers' predictive outcomes while neglecting the structural knowledge they encoded. This limitation makes such approach less effective when graphs become complex, particularly on heterogeneous graphs. Motivated by this challenge, we propose HGKD, a novel hierarchical knowledge distillation framework that transfers both structural knowledge and predictive outcomes from HGNN teachers to a multi-layer perceptron student. Additionally, we provide two variants of HGKD that help the student learn from multiple teacher models through Pareto learning and incorporate low-cost neighbor information. We evaluate HGKD and its variants on a range of heterogeneous graph datasets. The results demonstrate that our student model achieves performance comparable to or exceeding that of HGNN teachers, despite not relying on graph structures during inference.

Accurately predicting protein-ligand binding affinity is an important step in the drug discovery process. Deep learning (DL) methods have improved binding affinity prediction by using diverse categories of molecular data. However, many models rely heavily on interaction and sequence data, which impedes proper learning and limits performance in de novo applications. To address these limitations, we developed a novel graph neural network model, called StructureNet (structure-based graph neural network), to predict protein-ligand binding affinity. StructureNet improves existing DL methods by focusing entirely on structural descriptors to mitigate data memorization issues introduced by sequence and interaction data. StructureNet represents the protein and ligand structures as graphs, which are processed using a GNN-based ensemble deep learning model. StructureNet achieved a PCC of 0.68 and an AUC of 0.75 on the PDBBind v.2020 Refined Set, outperforming similar structure-based models. External validation on the DUDE-Z dataset showed that StructureNet can effectively distinguish between active and decoy ligands. Further testing on a small subset of well-known drugs indicates that StructureNet has high potential for rapid virtual screening applications. We also hybridized StructureNet with interaction- and sequence-based models to investigate their impact on testing accuracy and found minimal difference (0.01 PCC) between merged models and StructureNet as a standalone model. An ablation study found that geometric descriptors were the key drivers of model performance, with their removal leading to a PCC decrease of over 15.7%. Lastly, we tested StructureNet on ensembles of binding complex conformers generated using molecular dynamics (MD) simulations and found that incorporating multiple conformations of the same complex often improves model accuracy by capturing binding site flexibility. Overall, the results show that structural data alone are sufficient for binding affinity predictions and can address pattern recognition challenges introduced by sequence and interaction features. Additionally, structural representations of protein-ligand complexes can be considerably improved using geometric and topological descriptors. We made StructureNet GUI interface freely available online.

Pharmaceutical Applications of the Polarizable Amoeba Potential, Including Protein-Ligand Binding Affinity and Drug Solubility, using the Force Field X Software

Machine learning (ML) has been widely used for efficient resource allocation (RA) in wireless networks. Although superb performance is achieved on small and simple networks, most existing ML-based approaches are confronted with difficulties when heterogeneity occurs and network size expands. In this paper, specifically focusing on power control/beamforming (PC/BF) in heterogeneous device-to-device (D2D) networks, we propose a novel unsupervised learning-based framework named heterogeneous interference graph neural network (HIGNN) to handle these challenges. First, we characterize diversified link features and interference relations with heterogeneous graphs. Then, HIGNN is proposed to empower each link to obtain its individual transmission scheme after limited information exchange with neighboring links. It is noteworthy that HIGNN is scalable to wireless networks of growing sizes with robust performance after trained on small-sized networks. Numerical results show that compared with state-of-the-art benchmarks, HIGNN achieves much higher execution efficiency while providing strong performance.

Homophily, the tendency of similar nodes to connect, is a fundamental phenomenon in network science and a critical factor in the performance of graph neural networks (GNNs). While existing studies primarily explore homophily in homogeneous graphs, where nodes share the same type, real-world networks are often more accurately modeled as heterogeneous graphs (HGs) with diverse node types and intricate cross-type interactions. This structural diversity complicates the analysis of homophily, as traditional homophily metrics fail to account for distinct label spaces across node types. To address this limitation, we introduce the Cross-Type Homophily Ratio (CHR), a novel metric that quantifies homophily based on the similarity of target information across different node types. Additionally, we propose Cross-Type Homophily-guided Graph Editing (CTHGE), a novel method for improving heterogeneous graph neural networks (HGNNs) performance by optimizing cross-type connectivity using Cross-Type Homophily Ratio. Extensive experiments on five HG datasets with nine HGNNs validate the effectiveness of CTHGE, which delivers a maximum relative performance improvement of over 25% for HGNNs on node classification tasks, offering a fresh perspective on cross-type homophily in HGs learning.