Lirong Wu

Cheng Tan, Siyuan Li, Zhangyang Gao et al.

Spatio-temporal predictive learning is a learning paradigm that enables models to learn spatial and temporal patterns by predicting future frames from given past frames in an unsupervised manner. Despite remarkable progress in recent years, a lack of systematic understanding persists due to the diverse settings, complex implementation, and difficult reproducibility. Without standardization, comparisons can be unfair and insights inconclusive. To address this dilemma, we propose OpenSTL, a comprehensive benchmark for spatio-temporal predictive learning that categorizes prevalent approaches into recurrent-based and recurrent-free models. OpenSTL provides a modular and extensible framework implementing various state-of-the-art methods. We conduct standard evaluations on datasets across various domains, including synthetic moving object trajectory, human motion, driving scenes, traffic flow and weather forecasting. Based on our observations, we provide a detailed analysis of how model architecture and dataset properties affect spatio-temporal predictive learning performance. Surprisingly, we find that recurrent-free models achieve a good balance between efficiency and performance than recurrent models. Thus, we further extend the common MetaFormers to boost recurrent-free spatial-temporal predictive learning. We open-source the code and models at https://github.com/chengtan9907/OpenSTL.

Sitao Luan, Chenqing Hua, Qincheng Lu et al.

Homophily principle, \ie{} nodes with the same labels or similar attributes are more likely to be connected, has been commonly believed to be the main reason for the superiority of Graph Neural Networks (GNNs) over traditional Neural Networks (NNs) on graph-structured data, especially on node-level tasks. However, recent work has identified a non-trivial set of datasets where GNN's performance compared to the NN's is not satisfactory. Heterophily, i.e. low homophily, has been considered the main cause of this empirical observation. People have begun to revisit and re-evaluate most existing graph models, including graph transformer and its variants, in the heterophily scenario across various kinds of graphs, e.g. heterogeneous graphs, temporal graphs and hypergraphs. Moreover, numerous graph-related applications are found to be closely related to the heterophily problem. In the past few years, considerable effort has been devoted to studying and addressing the heterophily issue. In this survey, we provide a comprehensive review of the latest progress on heterophilic graph learning, including an extensive summary of benchmark datasets and evaluation of homophily metrics on synthetic graphs, meticulous classification of the most updated supervised and unsupervised learning methods, thorough digestion of the theoretical analysis on homophily/heterophily, and broad exploration of the heterophily-related applications. Notably, through detailed experiments, we are the first to categorize benchmark heterophilic datasets into three sub-categories: malignant, benign and ambiguous heterophily. Malignant and ambiguous datasets are identified as the real challenging datasets to test the effectiveness of new models on the heterophily challenge. Finally, we propose several challenges and future directions for heterophilic graph representation learning.

Lirong Wu, Yunfan Liu, Haitao Lin et al.

To bridge the gaps between powerful Graph Neural Networks (GNNs) and lightweight Multi-Layer Perceptron (MLPs), GNN-to-MLP Knowledge Distillation (KD) proposes to distill knowledge from a well-trained teacher GNN into a student MLP. In this paper, we revisit the knowledge samples (nodes) in teacher GNNs from the perspective of hardness, and identify that hard sample distillation may be a major performance bottleneck of existing graph KD algorithms. The GNN-to-MLP KD involves two different types of hardness, one student-free knowledge hardness describing the inherent complexity of GNN knowledge, and the other student-dependent distillation hardness describing the difficulty of teacher-to-student distillation. However, most of the existing work focuses on only one of these aspects or regards them as one thing. This paper proposes a simple yet effective Hardness-aware GNN-to-MLP Distillation (HGMD) framework, which decouples the two hardnesses and estimates them using a non-parametric approach. Finally, two hardness-aware distillation schemes (i.e., HGMD-weight and HGMD-mixup) are further proposed to distill hardness-aware knowledge from teacher GNNs into the corresponding nodes of student MLPs. As non-parametric distillation, HGMD does not involve any additional learnable parameters beyond the student MLPs, but it still outperforms most of the state-of-the-art competitors. HGMD-mixup improves over the vanilla MLPs by 12.95% and outperforms its teacher GNNs by 2.48% averaged over seven real-world datasets.

Cheng Tan, Zhenxiao Cao, Zhangyang Gao et al.

Post-translational modifications (PTMs) profoundly expand the complexity and functionality of the proteome, regulating protein attributes and interactions that are crucial for biological processes. Accurately predicting PTM sites and their specific types is therefore essential for elucidating protein function and understanding disease mechanisms. Existing computational approaches predominantly focus on protein sequences to predict PTM sites, driven by the recognition of sequence-dependent motifs. However, these approaches often overlook protein structural contexts. In this work, we first compile a large-scale sequence-structure PTM dataset, which serves as the foundation for fair comparison. We introduce the MeToken model, which tokenizes the micro-environment of each amino acid, integrating both sequence and structural information into unified discrete tokens. This model not only captures the typical sequence motifs associated with PTMs but also leverages the spatial arrangements dictated by protein tertiary structures, thus providing a holistic view of the factors influencing PTM sites. Designed to address the long-tail distribution of PTM types, MeToken employs uniform sub-codebooks that ensure even the rarest PTMs are adequately represented and distinguished. We validate the effectiveness and generalizability of MeToken across multiple datasets, demonstrating its superior performance in accurately identifying PTM types. The results underscore the importance of incorporating structural data and highlight MeToken's potential in facilitating accurate and comprehensive PTM predictions, which could significantly impact proteomics research. The code and datasets are available at https://github.com/A4Bio/MeToken.

Stan Z. Li, Zelin Zang, Lirong Wu

We propose a novel framework, called Markov-Lipschitz deep learning (MLDL), to tackle geometric deterioration caused by collapse, twisting, or crossing in vector-based neural network transformations for manifold-based representation learning and manifold data generation. A prior constraint, called locally isometric smoothness (LIS), is imposed across-layers and encoded into a Markov random field (MRF)-Gibbs distribution. This leads to the best possible solutions for local geometry preservation and robustness as measured by locally geometric distortion and locally bi-Lipschitz continuity. Consequently, the layer-wise vector transformations are enhanced into well-behaved, LIS-constrained metric homeomorphisms. Extensive experiments, comparisons, and ablation study demonstrate significant advantages of MLDL for manifold learning and manifold data generation. MLDL is general enough to enhance any vector transformation-based networks. The code is available at https://github.com/westlake-cairi/Markov-Lipschitz-Deep-Learning.

Haitao Lin, Odin Zhang, Huifeng Zhao et al.

Therapeutic peptides have proven to have great pharmaceutical value and potential in recent decades. However, methods of AI-assisted peptide drug discovery are not fully explored. To fill the gap, we propose a target-aware peptide design method called \textsc{PPFlow}, based on conditional flow matching on torus manifolds, to model the internal geometries of torsion angles for the peptide structure design. Besides, we establish a protein-peptide binding dataset named PPBench2024 to fill the void of massive data for the task of structure-based peptide drug design and to allow the training of deep learning methods. Extensive experiments show that PPFlow reaches state-of-the-art performance in tasks of peptide drug generation and optimization in comparison with baseline models, and can be generalized to other tasks including docking and side-chain packing.

Lirong Wu, Haitao Lin, Yufei Huang et al.

Antibodies are Y-shaped proteins that protect the host by binding to specific antigens, and their binding is mainly determined by the Complementary Determining Regions (CDRs) in the antibody. Despite the great progress made in CDR design, existing computational methods still encounter several challenges: 1) poor capability of modeling complex CDRs with long sequences due to insufficient contextual information; 2) conditioned on pre-given antigenic epitopes and their static interaction with the target antibody; 3) neglect of specificity during antibody optimization leads to non-specific antibodies. In this paper, we take into account a variety of node features, edge features, and edge relations to include more contextual and geometric information. We propose a novel Relation-Aware Antibody Design (RAAD) framework, which dynamically models antigen-antibody interactions for co-designing the sequences and structures of antigen-specific CDRs. Furthermore, we propose a new evaluation metric to better measure antibody specificity and develop a contrasting specificity-enhancing constraint to optimize the specificity of antibodies. Extensive experiments have demonstrated the superior capability of RAAD in terms of antibody modeling, generation, and optimization across different CDR types, sequence lengths, pre-training strategies, and input contexts.

Bozhen Hu, Zelin Zang, Jun Xia et al.

Representing graph data in a low-dimensional space for subsequent tasks is the purpose of attributed graph embedding. Most existing neural network approaches learn latent representations by minimizing reconstruction errors. Rare work considers the data distribution and the topological structure of latent codes simultaneously, which often results in inferior embeddings in real-world graph data. This paper proposes a novel Deep Manifold (Variational) Graph Auto-Encoder (DMVGAE/DMGAE) method for attributed graph data to improve the stability and quality of learned representations to tackle the crowding problem. The node-to-node geodesic similarity is preserved between the original and latent space under a pre-defined distribution. The proposed method surpasses state-of-the-art baseline algorithms by a significant margin on different downstream tasks across popular datasets, which validates our solutions. We promise to release the code after acceptance.

Lirong Wu, Yunfan Liu, Haitao Lin et al.

The proteins that exist today have been optimized over billions of years of natural evolution, during which nature creates random mutations and selects them. The discovery of functionally promising mutations is challenged by the limited evolutionary accessible regions, i.e., only a small region on the fitness landscape is beneficial. There have been numerous priors used to constrain protein evolution to regions of landscapes with high-fitness variants, among which the change in binding free energy (DDG) of protein complexes upon mutations is one of the most commonly used priors. However, the huge mutation space poses two challenges: (1) how to improve the efficiency of DDG prediction for fast mutation screening; and (2) how to explain mutation preferences and efficiently explore accessible evolutionary regions. To address these challenges, we propose a lightweight DDG predictor (Light-DDG), which adopts a structure-aware Transformer as the backbone and enhances it by knowledge distilled from existing powerful but computationally heavy DDG predictors. Additionally, we augmented, annotated, and released a large-scale dataset containing millions of mutation data for pre-training Light-DDG. We find that such a simple yet effective Light-DDG can serve as a good unsupervised antibody optimizer and explainer. For the target antibody, we propose a novel Mutation Explainer to learn mutation preferences, which accounts for the marginal benefit of each mutation per residue. To further explore accessible evolutionary regions, we conduct preference-guided antibody optimization and evaluate antibody candidates quickly using Light-DDG to identify desirable mutations.

Jun Xia, Lirong Wu, Jintao Chen et al.

Graph contrastive learning (GCL) has emerged as a dominant technique for graph representation learning which maximizes the mutual information between paired graph augmentations that share the same semantics. Unfortunately, it is difficult to preserve semantics well during augmentations in view of the diverse nature of graph data. Currently, data augmentations in GCL that are designed to preserve semantics broadly fall into three unsatisfactory ways. First, the augmentations can be manually picked per dataset by trial-and-errors. Second, the augmentations can be selected via cumbersome search. Third, the augmentations can be obtained by introducing expensive domain-specific knowledge as guidance. All of these limit the efficiency and more general applicability of existing GCL methods. To circumvent these crucial issues, we propose a \underline{Sim}ple framework for \underline{GRA}ph \underline{C}ontrastive l\underline{E}arning, \textbf{SimGRACE} for brevity, which does not require data augmentations. Specifically, we take original graph as input and GNN model with its perturbed version as two encoders to obtain two correlated views for contrast. SimGRACE is inspired by the observation that graph data can preserve their semantics well during encoder perturbations while not requiring manual trial-and-errors, cumbersome search or expensive domain knowledge for augmentations selection. Also, we explain why SimGRACE can succeed. Furthermore, we devise adversarial training scheme, dubbed \textbf{AT-SimGRACE}, to enhance the robustness of graph contrastive learning and theoretically explain the reasons. Albeit simple, we show that SimGRACE can yield competitive or better performance compared with state-of-the-art methods in terms of generalizability, transferability and robustness, while enjoying unprecedented degree of flexibility and efficiency.

Haitao Lin, Cheng Tan, Lirong Wu et al.

Temporal point process as the stochastic process on continuous domain of time is commonly used to model the asynchronous event sequence featuring with occurrence timestamps. Thanks to the strong expressivity of deep neural networks, they are emerging as a promising choice for capturing the patterns in asynchronous sequences, in the context of temporal point process. In this paper, we first review recent research emphasis and difficulties in modeling asynchronous event sequences with deep temporal point process, which can be concluded into four fields: encoding of history sequence, formulation of conditional intensity function, relational discovery of events and learning approaches for optimization. We introduce most of recently proposed models by dismantling them into the four parts, and conduct experiments by remodularizing the first three parts with the same learning strategy for a fair empirical evaluation. Besides, we extend the history encoders and conditional intensity function family, and propose a Granger causality discovery framework for exploiting the relations among multi-types of events. Because the Granger causality can be represented by the Granger causality graph, discrete graph structure learning in the framework of Variational Inference is employed to reveal latent structures of the graph. Further experiments show that the proposed framework with latent graph discovery can both capture the relations and achieve an improved fitting and predicting performance.

Lirong Wu, Haitao Lin, Zhangyang Gao et al.

Recent years have witnessed great success in handling node classification tasks with Graph Neural Networks (GNNs). However, most existing GNNs are based on the assumption that node samples for different classes are balanced, while for many real-world graphs, there exists the problem of class imbalance, i.e., some classes may have much fewer samples than others. In this case, directly training a GNN classifier with raw data would under-represent samples from those minority classes and result in sub-optimal performance. This paper presents GraphMixup, a novel mixup-based framework for improving class-imbalanced node classification on graphs. However, directly performing mixup in the input space or embedding space may produce out-of-domain samples due to the extreme sparsity of minority classes; hence we construct semantic relation spaces that allows the Feature Mixup to be performed at the semantic level. Moreover, we apply two context-based self-supervised techniques to capture both local and global information in the graph structure and then propose Edge Mixup specifically for graph data. Finally, we develop a \emph{Reinforcement Mixup} mechanism to adaptively determine how many samples are to be generated by mixup for those minority classes. Extensive experiments on three real-world datasets show that GraphMixup yields truly encouraging results for class-imbalanced node classification tasks.

Stan Z. Li, Lirong Wu, Zelin Zang

High dimensional data analysis for exploration and discovery includes three fundamental tasks: dimensionality reduction, clustering, and visualization. When the three associated tasks are done separately, as is often the case thus far, inconsistencies can occur among the tasks in terms of data geometry and others. This can lead to confusing or misleading data interpretation. In this paper, we propose a novel neural network-based method, called Consistent Representation Learning (CRL), to accomplish the three associated tasks end-to-end and improve the consistencies. The CRL network consists of two nonlinear dimensionality reduction (NLDR) transformations: (1) one from the input data space to the latent feature space for clustering, and (2) the other from the clustering space to the final 2D or 3D space for visualization. Importantly, the two NLDR transformations are performed to best satisfy local geometry preserving (LGP) constraints across the spaces or network layers, to improve data consistencies along with the processing flow. Also, we propose a novel metric, clustering-visualization inconsistency (CVI), for evaluating the inconsistencies. Extensive comparative results show that the proposed CRL neural network method outperforms the popular t-SNE and UMAP-based and other contemporary clustering and visualization algorithms in terms of evaluation metrics and visualization.

Stan Z. Li, Zelin Zang, Lirong Wu

Manifold learning-based encoders have been playing important roles in nonlinear dimensionality reduction (NLDR) for data exploration. However, existing methods can often fail to preserve geometric, topological and/or distributional structures of data. In this paper, we propose a deep manifold learning framework, called deep manifold transformation (DMT) for unsupervised NLDR and embedding learning. DMT enhances deep neural networks by using cross-layer local geometry-preserving (LGP) constraints. The LGP constraints constitute the loss for deep manifold learning and serve as geometric regularizers for NLDR network training. Extensive experiments on synthetic and real-world data demonstrate that DMT networks outperform existing leading manifold-based NLDR methods in terms of preserving the structures of data.

Siyuan Li, Haitao Lin, Zelin Zang et al.

Dimension reduction (DR) aims to learn low-dimensional representations of high-dimensional data with the preservation of essential information. In the context of manifold learning, we define that the representation after information-lossless DR preserves the topological and geometric properties of data manifolds formally, and propose a novel two-stage DR method, called invertible manifold learning (inv-ML) to bridge the gap between theoretical information-lossless and practical DR. The first stage includes a homeomorphic sparse coordinate transformation to learn low-dimensional representations without destroying topology and a local isometry constraint to preserve local geometry. In the second stage, a linear compression is implemented for the trade-off between the target dimension and the incurred information loss in excessive DR scenarios. Experiments are conducted on seven datasets with a neural network implementation of inv-ML, called i-ML-Enc. Empirically, i-ML-Enc achieves invertible DR in comparison with typical existing methods as well as reveals the characteristics of the learned manifolds. Through latent space interpolation on real-world datasets, we find that the reliability of tangent space approximated by the local neighborhood is the key to the success of manifold-based DR algorithms.

Lirong Wu, Kejie Huang, Haibin Shen et al.

The data storage has been one of the bottlenecks in surveillance systems. The conventional video compression algorithms such as H.264 and H.265 do not fully utilize the low information density characteristic of the surveillance video. In this paper, we propose a video compression method that extracts and compresses the foreground and background of the video separately. The compression ratio is greatly improved by sharing background information among multiple adjacent frames through an adaptive background updating and interpolation module. Besides, we present two different schemes to compress the foreground and compare their performance in the ablation study to show the importance of temporal information for video compression. In the decoding end, a coarse-to-fine two-stage module is applied to achieve the composition of the foreground and background and the enhancements of frame quality. Furthermore, an adaptive sampling method for surveillance cameras is proposed, and we have shown its effects through software simulation. The experimental results show that our proposed method requires 69.5% less bpp (bits per pixel) than the conventional algorithm H.265 to achieve the same PSNR (36 dB) on the HECV dataset.

Lirong Wu, Kejie Huang, Haibin Shen

The method of importance map has been widely adopted in DNN-based lossy image compression to achieve bit allocation according to the importance of image contents. However, insufficient allocation of bits in non-important regions often leads to severe distortion at low bpp (bits per pixel), which hampers the development of efficient content-weighted image compression systems. This paper rethinks content-based compression by using Generative Adversarial Network (GAN) to reconstruct the non-important regions. Moreover, multiscale pyramid decomposition is applied to both the encoder and the discriminator to achieve global compression of high-resolution images. A tunable compression scheme is also proposed in this paper to compress an image to any specific compression ratio without retraining the model. The experimental results show that our proposed method improves MS-SSIM by more than 10.3% compared to the recently reported GAN-based method to achieve the same low bpp (0.05) on the Kodak dataset.