Protein 3D Graph Structure Learning for Robust Structure-based Protein Property Prediction

Protein structure-based property prediction has emerged as a promising approach for various biological tasks, such as protein function prediction and sub-cellular location estimation. The existing methods highly rely on experimental protein structure data and fail in scenarios where these data are unavailable. Predicted protein structures from AI tools (e.g., AlphaFold2) were utilized as alternatives. However, we observed that current practices, which simply employ accurately predicted structures during inference, suffer from notable degradation in prediction accuracy. While similar phenomena have been extensively studied in general fields (e.g., Computer Vision) as model robustness, their impact on protein property prediction remains unexplored. In this paper, we first investigate the reason behind the performance decrease when utilizing predicted structures, attributing it to the structure embedding bias from the perspective of structure representation learning. To study this problem, we identify a Protein 3D Graph Structure Learning Problem for Robust Protein Property Prediction (PGSL-RP3), collect benchmark datasets, and present a protein Structure embedding Alignment Optimization framework (SAO) to mitigate the problem of structure embedding bias between the predicted and experimental protein structures. Extensive experiments have shown that our framework is model-agnostic and effective in improving the property prediction of both predicted structures and experimental structures. The benchmark datasets and codes will be released to benefit the community.

Revisiting the Temporal Modeling in Spatio-Temporal Predictive Learning under A Unified View

Spatio-temporal predictive learning plays a crucial role in self-supervised learning, with wide-ranging applications across a diverse range of fields. Previous approaches for temporal modeling fall into two categories: recurrent-based and recurrent-free methods. The former, while meticulously processing frames one by one, neglect short-term spatio-temporal information redundancies, leading to inefficiencies. The latter naively stack frames sequentially, overlooking the inherent temporal dependencies. In this paper, we re-examine the two dominant temporal modeling approaches within the realm of spatio-temporal predictive learning, offering a unified perspective. Building upon this analysis, we introduce USTEP (Unified Spatio-TEmporal Predictive learning), an innovative framework that reconciles the recurrent-based and recurrent-free methods by integrating both micro-temporal and macro-temporal scales. Extensive experiments on a wide range of spatio-temporal predictive learning demonstrate that USTEP achieves significant improvements over existing temporal modeling approaches, thereby establishing it as a robust solution for a wide range of spatio-temporal applications.

OpenSTL: A Comprehensive Benchmark of Spatio-Temporal Predictive Learning

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.

Quantifying the Knowledge in GNNs for Reliable Distillation into MLPs

To bridge the gaps between topology-aware Graph Neural Networks (GNNs) and inference-efficient Multi-Layer Perceptron (MLPs), GLNN proposes to distill knowledge from a well-trained teacher GNN into a student MLP. Despite their great progress, comparatively little work has been done to explore the reliability of different knowledge points (nodes) in GNNs, especially their roles played during distillation. In this paper, we first quantify the knowledge reliability in GNN by measuring the invariance of their information entropy to noise perturbations, from which we observe that different knowledge points (1) show different distillation speeds (temporally); (2) are differentially distributed in the graph (spatially). To achieve reliable distillation, we propose an effective approach, namely Knowledge-inspired Reliable Distillation (KRD), that models the probability of each node being an informative and reliable knowledge point, based on which we sample a set of additional reliable knowledge points as supervision for training student MLPs. Extensive experiments show that KRD improves over the vanilla MLPs by 12.62% and outperforms its corresponding teacher GNNs by 2.16% averaged over 7 datasets and 3 GNN architectures.

Extracting Low-/High- Frequency Knowledge from Graph Neural Networks and Injecting it into MLPs: An Effective GNN-to-MLP Distillation Framework

Recent years have witnessed the great success of Graph Neural Networks (GNNs) in handling graph-related tasks. However, MLPs remain the primary workhorse for practical industrial applications due to their desirable inference efficiency and scalability. To reduce their gaps, one can directly distill knowledge from a well-designed teacher GNN to a student MLP, which is termed as GNN-to-MLP distillation. However, the process of distillation usually entails a loss of information, and ``which knowledge patterns of GNNs are more likely to be left and distilled into MLPs?" becomes an important question. In this paper, we first factorize the knowledge learned by GNNs into low- and high-frequency components in the spectral domain and then derive their correspondence in the spatial domain. Furthermore, we identified a potential information drowning problem for existing GNN-to-MLP distillation, i.e., the high-frequency knowledge of the pre-trained GNNs may be overwhelmed by the low-frequency knowledge during distillation; we have described in detail what it represents, how it arises, what impact it has, and how to deal with it. In this paper, we propose an efficient Full-Frequency GNN-to-MLP (FF-G2M) distillation framework, which extracts both low-frequency and high-frequency knowledge from GNNs and injects it into MLPs. Extensive experiments show that FF-G2M improves over the vanilla MLPs by 12.6% and outperforms its corresponding teacher GNNs by 2.6% averaged over six graph datasets and three common GNN architectures.

Towards Reasonable Budget Allocation in Untargeted Graph Structure Attacks via Gradient Debias

It has become cognitive inertia to employ cross-entropy loss function in classification related tasks. In the untargeted attacks on graph structure, the gradients derived from the attack objective are the attacker's basis for evaluating a perturbation scheme. Previous methods use negative cross-entropy loss as the attack objective in attacking node-level classification models. However, the suitability of the cross-entropy function for constructing the untargeted attack objective has yet been discussed in previous works. This paper argues about the previous unreasonable attack objective from the perspective of budget allocation. We demonstrate theoretically and empirically that negative cross-entropy tends to produce more significant gradients from nodes with lower confidence in the labeled classes, even if the predicted classes of these nodes have been misled. To free up these inefficient attack budgets, we propose a simple attack model for untargeted attacks on graph structure based on a novel attack objective which generates unweighted gradients on graph structures that are not affected by the node confidence. By conducting experiments in gray-box poisoning attack scenarios, we demonstrate that a reasonable budget allocation can significantly improve the effectiveness of gradient-based edge perturbations without any extra hyper-parameter.

Data-Efficient Protein 3D Geometric Pretraining via Refinement of Diffused Protein Structure Decoy

Learning meaningful protein representation is important for a variety of biological downstream tasks such as structure-based drug design. Having witnessed the success of protein sequence pretraining, pretraining for structural data which is more informative has become a promising research topic. However, there are three major challenges facing protein structure pretraining: insufficient sample diversity, physically unrealistic modeling, and the lack of protein-specific pretext tasks. To try to address these challenges, we present the 3D Geometric Pretraining. In this paper, we propose a unified framework for protein pretraining and a 3D geometric-based, data-efficient, and protein-specific pretext task: RefineDiff (Refine the Diffused Protein Structure Decoy). After pretraining our geometric-aware model with this task on limited data(less than 1% of SOTA models), we obtained informative protein representations that can achieve comparable performance for various downstream tasks.

Explaining Graph Neural Networks via Non-parametric Subgraph Matching

The great success in graph neural networks (GNNs) provokes the question about explainability: Which fraction of the input graph is the most determinant of the prediction? Particularly, parametric explainers prevail in existing approaches because of their stronger capability to decipher the black-box (i.e., the target GNN). In this paper, based on the observation that graphs typically share some joint motif patterns, we propose a novel non-parametric subgraph matching framework, dubbed MatchExplainer, to explore explanatory subgraphs. It couples the target graph with other counterpart instances and identifies the most crucial joint substructure by minimizing the node corresponding-based distance. Moreover, we note that present graph sampling or node-dropping methods usually suffer from the false positive sampling problem. To ameliorate that issue, we design a new augmentation paradigm named MatchDrop. It takes advantage of MatchExplainer to fix the most informative portion of the graph and merely operates graph augmentations on the rest less informative part. We conduct extensive experiments on both synthetic and real-world datasets and show the effectiveness of our MatchExplainer by outperforming all parametric baselines with significant margins. Additional results also demonstrate that our MatchDrop is a general scheme to be equipped with GNNs for enhanced performance.

A Survey on Protein Representation Learning: Retrospect and Prospect

Proteins are fundamental biological entities that play a key role in life activities. The amino acid sequences of proteins can be folded into stable 3D structures in the real physicochemical world, forming a special kind of sequence-structure data. With the development of Artificial Intelligence (AI) techniques, Protein Representation Learning (PRL) has recently emerged as a promising research topic for extracting informative knowledge from massive protein sequences or structures. To pave the way for AI researchers with little bioinformatics background, we present a timely and comprehensive review of PRL formulations and existing PRL methods from the perspective of model architectures, pretext tasks, and downstream applications. We first briefly introduce the motivations for protein representation learning and formulate it in a general and unified framework. Next, we divide existing PRL methods into three main categories: sequence-based, structure-based, and sequence-structure co-modeling. Finally, we discuss some technical challenges and potential directions for improving protein representation learning. The latest advances in PRL methods are summarized in a GitHub repository https://github.com/LirongWu/awesome-protein-representation-learning.

Non-equispaced Fourier Neural Solvers for PDEs

Solving partial differential equations is difficult. Recently proposed neural resolution-invariant models, despite their effectiveness and efficiency, usually require equispaced spatial points of data. However, sampling in spatial domain is sometimes inevitably non-equispaced in real-world systems, limiting their applicability. In this paper, we propose a Non-equispaced Fourier PDE Solver (\textsc{NFS}) with adaptive interpolation on resampled equispaced points and a variant of Fourier Neural Operators as its components. Experimental results on complex PDEs demonstrate its advantages in accuracy and efficiency. Compared with the spatially-equispaced benchmark methods, it achieves superior performance with $42.85\%$ improvements on MAE, and is able to handle non-equispaced data with a tiny loss of accuracy. Besides, to our best knowledge, \textsc{NFS} is the first ML-based method with mesh invariant inference ability to successfully model turbulent flows in non-equispaced scenarios, with a minor deviation of the error on unseen spatial points.