Understanding and continuously refining multimodal molecular knowledge is crucial for advancing biomedicine, chemistry, and materials science. Molecule language models (MoLMs) have become powerful tools in these domains, integrating structural representations (e.g., SMILES strings, molecular graphs) with rich contextual descriptions (e.g., physicochemical properties, biomedical applications). However, MoLMs can encode and propagate inaccuracies due to outdated web-mined training corpora or malicious manipulation, jeopardizing downstream discovery pipelines. While knowledge editing has been explored for general-domain AI, its application to MoLMs remains uncharted, presenting unique challenges due to the multifaceted and interdependent nature of molecular knowledge. In this paper, we take the first step toward MoLM editing for two critical tasks: molecule-to-caption generation and caption-to-molecule generation. To address molecule-specific challenges, we propose MolEdit, a powerful framework that enables targeted modifications while preserving unrelated molecular knowledge. MolEdit combines a Multi-Expert Knowledge Adapter that routes edits to specialized experts for different molecular facets with an Expertise-Aware Editing Switcher that activates the adapters only when input closely matches the stored edits across all expertise, minimizing interference with unrelated knowledge. To systematically evaluate editing performance, we introduce MEBench, a comprehensive benchmark assessing multiple dimensions, including Reliability (accuracy of the editing), Locality (preservation of irrelevant knowledge), and Generality (robustness to reformed queries). Across extensive experiments on two popular MoLM backbones, MolEdit delivers up to 18.8 % higher Reliability and 12.0 % better Locality than state-of-the-art editing baselines while maintaining efficiency. Our findings chart a clear path toward safer, continuously updatable scientific foundation models. The code is available at: https://github.com/LzyFischer/MolEdit.

Federated Graph Learning (FGL) enables multiple clients to jointly train powerful graph learning models, e.g., Graph Neural Networks (GNNs), without sharing their local graph data for graph-related downstream tasks, such as graph property prediction. In the real world, however, the graph data can suffer from significant distribution shifts across clients as the clients may collect their graph data for different purposes. In particular, graph properties are usually associated with invariant label-relevant substructures (i.e., subgraphs) across clients, while label-irrelevant substructures can appear in a client-specific manner. The issue of distribution shifts of graph data hinders the efficiency of GNN training and leads to serious performance degradation in FGL. To tackle the aforementioned issue, we propose a novel FGL framework entitled FedVN that eliminates distribution shifts through client-specific graph augmentation strategies with multiple learnable Virtual Nodes (VNs). Specifically, FedVN lets the clients jointly learn a set of shared VNs while training a global GNN model. To eliminate distribution shifts, each client trains a personalized edge generator that determines how the VNs connect local graphs in a client-specific manner. Furthermore, we provide theoretical analyses indicating that FedVN can eliminate distribution shifts of graph data across clients. Comprehensive experiments on four datasets under five settings demonstrate the superiority of our proposed FedVN over nine baselines.

Graph Neural Networks (GNNs) have achieved remarkable success in various graph-based learning tasks. While their performance is often attributed to the powerful neighborhood aggregation mechanism, recent studies suggest that other components such as non-linear layers may also significantly affecting how GNNs process the input graph data in the spectral domain. Such evidence challenges the prevalent opinion that neighborhood aggregation mechanisms dominate the behavioral characteristics of GNNs in the spectral domain. To demystify such a conflict, this paper introduces a comprehensive benchmark to measure and evaluate GNNs' capability in capturing and leveraging the information encoded in different frequency components of the input graph data. Specifically, we first conduct an exploratory study demonstrating that GNNs can flexibly yield outputs with diverse frequency components even when certain frequencies are absent or filtered out from the input graph data. We then formulate a novel research problem of measuring and benchmarking the performance of GNNs from a spectral perspective. To take an initial step towards a comprehensive benchmark, we design an evaluation protocol supported by comprehensive theoretical analysis. Finally, we introduce a comprehensive benchmark on real-world datasets, revealing insights that challenge prevalent opinions from a spectral perspective. We believe that our findings will open new avenues for future advancements in this area. Our implementations can be found at: https://github.com/yushundong/Spectral-benchmark.

Pre-training powerful Graph Neural Networks (GNNs) with unlabeled graph data in a self-supervised manner has emerged as a prominent technique in recent years. However, inevitable objective gaps often exist between pre-training and downstream tasks. To bridge this gap, graph prompt tuning techniques design and learn graph prompts by manipulating input graphs or reframing downstream tasks as pre-training tasks without fine-tuning the pre-trained GNN models. While recent graph prompt tuning methods have proven effective in adapting pre-trained GNN models for downstream tasks, they overlook the crucial role of edges in graph prompt design, which can significantly affect the quality of graph representations for downstream tasks. In this study, we propose EdgePrompt, a simple yet effective graph prompt tuning method from the perspective of edges. Unlike previous studies that design prompt vectors on node features, EdgePrompt manipulates input graphs by learning additional prompt vectors for edges and incorporates the edge prompts through message passing in the pre-trained GNN models to better embed graph structural information for downstream tasks. Our method is compatible with prevalent GNN architectures pre-trained under various pre-training strategies and is universal for different downstream tasks. We provide comprehensive theoretical analyses of our method regarding its capability of handling node classification and graph classification as downstream tasks. Extensive experiments on ten graph datasets under four pre-training strategies demonstrate the superiority of our proposed method against six baselines. Our code is available at https://github.com/xbfu/EdgePrompt.

Mechanistic interpretability (MI) research aims to understand large language models (LLMs) by identifying computational circuits, subgraphs of model components with associated functional interpretations, that explain specific behaviors. Current MI approaches focus on discovering task-specific circuits, which has two key limitations: (1) poor generalizability across different language tasks, and (2) high costs associated with requiring human or advanced LLM interpretation of each computational node. To address these challenges, we propose developing a “modular circuit (MC) vocabulary” consisting of task-agnostic functional units. Each unit consists of a small computational subgraph with its interpretation. This approach enables global interpretability by allowing different language tasks to share common MCs, while reducing costs by reusing established interpretations for new tasks. We establish five criteria for characterizing the MC vocabulary and present ModCirc, a novel global-level mechanistic interpretability framework for discovering MC vocabularies in LLMs. We demonstrate ModCirc’s effectiveness by showing that it can identify modular circuits that perform well on various metrics.

Predicting changes in binding free energy (ΔΔ G) is a vital task in protein engineering and protein-protein interaction (PPI) engineering for drug discovery. Previous works have observed a high correlation between ΔΔ G and entropy, using probabilities of biologically important objects such as side chain angles and residue identities to estimate ΔΔ G. However, estimating the full conformational distribution of a protein complex is generally considered intractable. In this work, we propose a new approach to ΔΔ G prediction that avoids this issue by instead leveraging energy-based models for estimating the probability of a complex's conformation. Specifically, we novelly decompose ΔΔ G into a sequence-based component estimated by an inverse folding model and a structure-based component estimated by an energy model. This decomposition is made tractable by assuming equilibrium between the bound and unbound states, allowing us to simplify the estimation of degeneracies associated with each state. Unlike previous deep learning-based methods, our method incorporates an energy-based physical inductive bias by connecting the often-used sequence log-odds ratio-based approach to ΔΔ G prediction with a new ΔΔ E term grounded in statistical mechanics. We demonstrate superiority over existing state-of-the-art structure and sequence-based deep learning methods in ΔΔ G prediction and antibody optimization against SARS-CoV-2.

In-Context Learning (ICL) is a technique where large language models (LLMs) leverage multiple demonstrations (i.e., examples) to perform tasks. With the recent expansion of LLM context windows, many-shot ICL (generally with more than 50 demonstrations) can lead to significant performance improvements on a variety of language tasks such as text classification and question answering. Nevertheless, ICL faces the issue of demonstration order instability (ICL-DOI), which means that performance varies significantly depending on the order of demonstrations. Moreover, ICL-DOI persists in many-shot ICL, validated by our thorough experimental investigation. Current strategies for handling ICL-DOI are not applicable to many-shot ICL due to two critical challenges: (1) Most existing methods assess demonstration order quality by first prompting the LLM, then using heuristic metrics based on the LLM's predictions. In the many-shot scenarios, these metrics without theoretical grounding become unreliable, where the LLMs struggle to effectively utilize information from long input contexts, making order distinctions less clear. The requirement to examine all orders for the large number of demonstrations is computationally infeasible due to the super-exponential complexity of the order space in many-shot ICL. To tackle the first challenge, we design a demonstration order evaluation metric based on information theory for measuring order quality, which effectively quantifies the usable information gain of a given demonstration order. To address the second challenge, we propose a hierarchical demonstration order optimization method named \texttt{HIDO} that enables a more refined exploration of the order space, achieving high ICL performance without the need to evaluate all possible orders. Extensive experiments on multiple LLMs and real-world datasets demonstrate that our \texttt{HIDO} method consistently and efficiently outperforms other baselines. Our code project can be found at https://github.com/YinhanHe123/HIDO/.

Chain-of-Thought (CoT) enhances the performance of Large Language Models (LLMs) on reasoning tasks by encouraging step-by-step solutions. However, the verbosity of CoT reasoning hinders its mass deployment in efficiency-critical applications. Recently, implicit CoT approaches have emerged, which encode reasoning steps within LLM's hidden embeddings (termed ``implicit reasoning'') rather than explicit tokens. This approach accelerates CoT reasoning by reducing the reasoning length and bypassing some LLM components. However, existing implicit CoT methods face two significant challenges: (1) they fail to preserve the semantic alignment between the implicit reasoning (when transformed to natural language) and the ground-truth reasoning, resulting in a significant CoT performance degradation, and (2) they focus on reducing the length of the implicit reasoning; however, they neglect the considerable time cost for an LLM to generate one individual implicit reasoning token. To tackle these challenges, we propose a novel semantically-aligned implicit CoT framework termed **SemCoT**. In particular, for the first challenge, we design a contrastively trained sentence transformer that evaluates semantic alignment between implicit and explicit reasoning, which is used to enforce semantic preservation during implicit reasoning optimization. To address the second challenge, we introduce an efficient implicit reasoning generator by finetuning a lightweight language model using knowledge distillation. This generator is guided by our sentence transformer to distill ground-truth reasoning into semantically aligned implicit reasoning, while also optimizing for accuracy. SemCoT is the first approach that enhances CoT efficiency by jointly optimizing token-level generation speed and preserving semantic alignment with ground-truth reasoning. Extensive experiments demonstrate the superior performance of SemCoT compared to state-of-the-art methods in both efficiency and effectiveness. Our code can be found at https://github.com/YinhanHe123/SemCoT/.

Computational epidemiology is crucial in understanding and controlling infectious diseases, as highlighted by large-scale outbreaks such as COVID-19. Given the inherent uncertainty and variability of disease spread, Monte Carlo (MC) simulations are widely used to predict infection peaks, estimate reproduction numbers, and evaluate the impact of non-pharmaceutical interventions (NPIs). While effective, MC-based methods require numerous runs to achieve statistically reliable estimates and variance, which suffer from high computational costs. In this work, we present a unified theoretical framework for analyzing disease spread dynamics on both directed and undirected contact networks, and propose an algorithm, **RAPID**, that significantly improves computational efficiency. Our contributions are threefold. First, we derive an asymptotic variance lower bound for MC estimates and identify the key factors influencing estimation variance. Second, we provide a theoretical analysis of the probabilistic disease spread process using linear approximations and derive the convergence conditions under non-reinfection epidemic models. Finally, we conduct extensive experiments on six real-world datasets, demonstrating our method's effectiveness and robustness in estimating the nodes' final state distribution. Specifically, our proposed method consistently produces accurate estimates aligned with results from a large number of MC simulations, while maintaining a runtime comparable to a single MC simulation. Our code and datasets are available at https://github.com/GuanghuiMin/RAPID.

Epidemic containment has long been a crucial task in many high-stake application domains, ranging from public health to misinformation dissemination. Existing studies for epidemic containment are primarily focused on undirected networks, assuming that the infection rate is constant throughout the contact network regardless of the strength and direction of contact. However, such an assumption can be unrealistic given the asymmetric nature of the real-world infection process. To tackle the epidemic containment problem in directed networks, simply grafting the methods designed for undirected network can be problematic, as most of the existing methods rely on the orthogonality and Lipschitz continuity in the eigensystem of the underlying contact network, which do not hold for directed networks. In this work, we derive a theoretical analysis on the general epidemic threshold condition for directed networks and show that such threshold condition can be used as an optimization objective to control the spread of the disease. Based on the epidemic threshold, we propose an asymptotically greedy algorithm DINO (DIrected NetwOrk epidemic containment) to identify the most critical nodes for epidemic containment. The proposed algorithm is evaluated on real-world directed networks, and the results validate its effectiveness and efficiency. The code is available at https://github.com/YinhanHe123/DINO/.

Causality lays the foundation for the trajectory of our world. Causal inference (CI), which aims to infer intrinsic causal relations among variables of interest, has emerged as a crucial research topic. Nevertheless, the lack of observation of important variables (e.g., confounders, mediators, exogenous variables, etc.) severely compromises the reliability of CI methods. The issue may arise from the inherent difficulty in measuring the variables. Additionally, in observational studies where variables are passively recorded, certain covariates might be inadvertently omitted by the experimenter. Depending on the type of unobserved variables and the specific CI task, various consequences can be incurred if these latent variables are carelessly handled, such as biased estimation of causal effects, incomplete understanding of causal mechanisms, lack of individual-level causal consideration, etc. In this survey, we provide a comprehensive review of recent developments in CI with latent variables. We start by discussing traditional CI techniques when variables of interest are assumed to be fully observed. Afterward, under the taxonomy of circumvention and inference-based methods, we provide an in-depth discussion of various CI strategies to handle latent variables, covering the tasks of causal effect estimation, mediation analysis, counterfactual reasoning, and causal discovery. Furthermore, we generalize the discussion to graph data where interference among units may exist. Finally, we offer fresh aspects for further advancement of CI with latent variables, especially new opportunities in the era of large language models (LLMs).