The field of knowledge graph representation learning (KGRL) has been rapidly expanding. To effectively apply KGRL models to large real-world knowledge graphs (KGs), anchor-based methods have been proposed. These methods aim to reduce computational costs and parameter requirements by encoding entities using a small set of entity anchors. However, existing anchor selection approaches are often rudimentary and sometimes yield suboptimal results. In this article, we propose a scalable anchor-based KGRL method called SKIP. By leveraging prototype information, our method selects representative entities as anchors. The SKIP method consists of two main steps. First, pretraining models are employed to encode entities by utilizing the topological structure and textual information in KGs. Second, the prototype learning module (PLM) extracts entity prototypes, which are then used to sample entity anchors that contain valuable prototype information. These settings enable SKIP to identify representative and reasonable entity anchors, leading to improved performance while requiring fewer computational resources. Extensive experiments conducted on various downstream tasks using KGs of different scales demonstrate the superiority and effectiveness of SKIP. Particularly, on the large OGB WikiKG 2 dataset, our method achieves comparable performance while reducing running time by approximately 21.28% and requiring 21.43% fewer model parameters compared to the baseline. This indicates the superior scalability of SKIP.

Nuclear Magnetic Resonance (NMR) spectroscopy is the gold standard for molecular structure elucidation, yet interpreting complex spectra for unknown molecules remains a bottleneck reliant on human expertise. While artificial intelligence has advanced this field, current methods face a critical trade-off: database retrieval cannot identify novel scaffolds, while de novo molecular structure elucidation models operate as black boxes, lacking the atom-level interpretability required for rigorous scientific validation. Here, we present NMRAgent, an evidential reasoning agent powered by large language models (LLMs) that bridges this gap by integrating specialized spectral analysis tools with chemical knowledge graphs. Unlike previous approaches, NMRAgent mimics the deductive reasoning of human experts: it takes experimental NMR spectra and molecular formula as input, plans the elucidation process, proposes candidate structures, verifies peak-atom consistency, and refines misaligned substructure through formula-aware fragment optimization. Enabled by its evidential reasoning, NMRAgent outperforms state-of-the-art methods, improving top-1 accuracy by 46.5

Tandem mass spectrometry (MS/MS) is central to small molecule identification, but current deep learning systems for spectrum prediction still remain difficult to evaluate and deploy in practice. While novel architectures constantly claim state-of-the-art performance, inconsistent metadata conditioning and entangled preprocessing pipelines hinder fair architectural comparisons. Besides, existing evaluations are often restricted to curated datasets, failing to capture the heterogeneity and cross-domain shifts of real-world metabolomics. Furthermore, current benchmarks lack difficulty-aware diagnostics and leave blind to how models behave under specific compute or data constraints. To address this, we present FlexMS, a modular public-data benchmark framework that standardizes MS/MS prediction across public resources while keeping molecular encoders, metadata conditioning, predictor heads, and downstream retrieval under one protocol. FlexMS establishes a fair evaluation playground which significantly lowers the barrier for integrating new predictive tools. Rather than solely optimizing for average scores, FlexMS augments aggregate accuracy with difficulty-aware diagnostics, providing actionable guidance on model selection across different compute constraints, data scales, and downstream retrieval objectives. Ultimately, FlexMS provides the community with a reproducible standard to identify which algorithmic conclusions are stable and which operating points are most viable in practice.

Molecular interactions are a common phenomenon in physical chemistry field, which could produce unexpected biochemical properties harmful to humans, such as drug-drug interactions. Machine learning has the potential to deliver rapid and accurate predictions. However, the complexity of molecular structures and the diversity of molecular interactions could undermine model prediction accuracy and hinder generalizability. In this context, identifying core invariant substructures (\textit{i.e.}, rationales) has become essential for enhancing interpretability and generalization. Despite notable efforts, existing models often neglect the molecular pairs’ modeling, leading to insufficient capture of interaction relationships. To address these limitations, we propose a novel framework, \textbf{I}nteraction-aware \textbf{I}nvariant \textbf{Mole}cular learning (I2Mole), for generalizable property prediction. I2Mole meticulously models atomic interactions such as hydrogen bonds by initially establishing indiscriminate connections between intermolecular atoms, which are subsequently refined using an improved graph information bottleneck theory tailored for merged graphs. To further enhance model generalization, we construct an environment codebook by environment subgraph of the merged graph. This approach not only could provide noise source for optimizing mutual information but also preserve the integrity of chemical semantic information. By comprehensively leveraging the information inherent in the merged graph, our model accurately captures core substructures and significantly enhances generalization capabilities. Extensive experimental validation demonstrates the efficacy and generalizability of I2Mole. The implementation code is available.

Large Reasoning Models (LRMs) significantly improve the reasoning ability of Large Language Models (LLMs) by learning to reason, exhibiting promising performance in solving complex tasks. However, their deliberative reasoning process leads to inefficiencies in token usage, memory consumption, and inference time. Thus, this survey provides a review of efficient inference methods designed specifically for LRMs, focusing on mitigating token inefficiency while preserving the reasoning quality. The overview structure of this paper is shown in Figure 1. First, we introduce a taxonomy to group the recent methods into two main categories: (a) explicit compact Chain-of-Thought (CoT), which reduces tokens while keeping the explicit reasoning structure, and (b) implicit latent CoT, which encodes reasoning steps within hidden representations instead of explicit tokens. Meanwhile, we discuss their strengths and weaknesses. Then, we conduct empirical analyses on existing methods from reasoning scenarios, object functions, and performance & efficiency aspects. Besides, we present open challenges in this field, including human-centric controllable reasoning, trade-off between interpretability and efficiency of reasoning, ensuring the safety of efficient reasoning, and broader applications of efficient reasoning. In addition, we highlight key insights for enhancing LRMs' inference efficiency via techniques such as model merging, new architectures, and agent routers. We hope this work serves as a valuable guide, helping researchers overcome challenges in this vibrant field. A collection of efficient reasoning methods for LRMs (papers and codes) is provided at this link: https://github.com/yueliu1999/Awesome-Efficient-Inference-for-LRMs.

Infrared (IR) spectra provide characteristic signals of molecular structure, which are often interpreted by experts via functional-group identification or library matching, making the process time-consuming and ambiguous. Recent machine learning methods have made progress in molecular structure elucidation using molecular formulas and IR spectra. However, these models often infer unreasonable candidate molecular structures, including top-ranked predictions. More specifically, the molecular formula implied by a candidate structure often fails to match the input molecular formula, and the candidate's theoretical IR spectrum is often inconsistent with the observed IR spectrum. To address these issues, we propose Formula- and IR-Matched Preference Optimization (FIRMPO), a general and plug-and-play chemical feedback-driven preference optimization framework for molecular structure elucidation. FIRMPO incorporates chemical feedback as preference signals based on exact molecular formula matching and IR spectral consistency to guide reasonable structure predictions. Unlike generic preference optimization methods, FIRMPO is tailored to molecular structure elucidation while remaining model-agnostic, enabling it to be readily integrated with different structure prediction models in this class. This encourages models to prioritize structures that satisfy the chemical feedback, leading to a substantial improvement in the accuracy of top-ranked predictions. Extensive experiments on three widely used IR datasets show that FIRMPO significantly improves molecular structure elucidation accuracy over existing baselines.

Multimodal large language models (MLLMs) are increasingly required to adapt to non-stationary streams of visual domains, question types, and user instructions, yet continual fine-tuning often causes severe forgetting of previously acquired multimodal skills. Existing continual vision-language methods mainly preserve outputs, replay data or pseudo-data, regularize embedding geometry, or allocate task-specific parameters, but they provide limited control over how internal cross-modal attention patterns supporting old skills drift during adaptation. We propose Attention-Spectrum Regularization (ASR), a replay-free continual learning framework that preserves skill-conditioned structures of cross-modal attention. ASR treats cross-attention maps as two-dimensional signals, summarizes their scale and directional properties into compact spectral statistics, and stores only skill-wise prototype distributions instead of replaying past image-question pairs, generated pseudo-examples, or old-stage teacher snapshots. In later stages, a phase-invariant spectral regularizer constrains harmful drift of these prototypes while allowing instance-level attention to adapt to new tasks. We provide theoretical analysis showing that skill-conditioned spectral drift controls forgetting under a spectral sufficiency assumption, and that Fourier power spectra are stable to spatial translations and bounded perturbations. Experiments on continual VQA and multimodal instruction-tuning benchmarks, including VQA v2, VQACL, CLT-VQA, CoIN, and UCIT, show that ASR consistently improves final performance and reduces forgetting over strong replay-, regularization-, and adapter-based baselines. Preserving skill-level attention structure is an effective and lightweight mechanism for continual MLLMs. Code is available at https://github.com/Creative-zcx/attention-spectrum-replay

De novo peptide sequencing from tandem mass spectrometry is pivotal in proteomics, enabling identification of novel peptides without reference databases. While recent Transformer-based encoder-decoder models have achieved remarkable performance, we uncover a critical pathology in their inference dynamics. Through comprehensive feature scaling experiments, we demonstrate that existing auto-regressive peptide decoders tend to over-rely on generated-sequence priors while progressively under-utilizing fine-grained physical evidence from the input mass spectrum. This phenomenon leads to suboptimal results, where generated peptide sequences are biologically plausible yet not faithful to the input spectrum. To rectify this, we propose MemNovo, a training-free and plug-and-play mechanism that re-balances peptide and spectral contributions at inference time. MemNovo alleviates the information bottleneck by establishing a persistent spectral memory bank and injecting retrieved features directly into the final decoding stage via an ultra-conservative residual connection. Theoretical analysis confirms that this mechanism restores the mutual information between the decoder state and the raw spectrum. Extensive experiments on the Nine Species benchmark with two representative baselines, Casanovo and InstaNovo, demonstrate that MemNovo consistently improves both amino acid precision and peptide precision, achieving up to 39.1

Protein inverse folding aims to design an amino acid sequence that will fold into a given backbone structure, serving as a central task in protein design. Two main paradigms have been widely explored. Template-based methods exploit database-derived structural priors and can achieve high local precision when close structural neighbors are available, but their dependence on database coverage and match quality often degrades performance on out-of-distribution (OOD) targets. Deep learning approaches, in contrast, learn general structure-to-sequence regularities and usually generalize better to new backbones. However, they struggle to capture fine-grained local structure, which can cause uncertain residue predictions and missed local motifs in ambiguous regions. We introduce Refold, a novel framework that synergistically integrates the strengths of database-derived structural priors and deep learning prediction to enhance inverse folding. Refold obtains structural priors from matched neighbors and fuses them with model predictions to refine residue probabilities. In practice, low-quality neighbors can introduce noise, potentially degrading model performance. We address this issue with a Dynamic Utility Gate that controls prior injection and falls back to the base prediction when the priors are untrustworthy. Comprehensive evaluations on standard benchmarks demonstrate that Refold achieves state-of-the-art native sequence recovery of 0.63 on both CATH 4.2 and CATH 4.3. Also, analysis indicates that Refold delivers larger gains on high-uncertainty regions, reflecting the complementarity between structural priors and deep learning predictions.

Graph clustering, which aims to divide nodes in the graph into several distinct clusters, is a fundamental yet challenging task. Benefiting from the powerful representation capability of deep learning, deep graph clustering (DGC) methods have achieved great success in recent years. However, the corresponding survey paper is relatively scarce, and it is imminent to make a summary of this field. From this motivation, we conduct a comprehensive survey of DGC. Firstly, we introduce formulaic definition, evaluation, and development in this field. Secondly, the taxonomy of DGC methods is presented based on four different criteria, including graph type, network architecture, learning paradigm, and clustering method. Thirdly, we carefully analyze the existing methods via extensive experiments and summarize the challenges and opportunities from five perspectives, including graph data quality, stability, scalability, discriminative capability, and unknown cluster number. Besides, the applications of DGC methods in six domains, including computer vision, natural language processing, recommendation systems, social network analysis, bioinformatics, and medical science, are presented. Last but not least, this paper provides open resource supports, including 1) a collection of state-of-the-art DGC methods (papers, codes, and datasets) and 2) a flexible and extensible Python library for DGC. We hope this work can serve as a quick guide and help researchers overcome challenges in this vibrant field.

The discovery of novel proteins relies on sensitive protein identification, for which de novo peptide sequencing (DNPS) from mass spectra is a crucial approach. While deep learning has advanced DNPS, existing models inadequately enforce the fundamental mass consistency constraint, that a predicted peptide's mass must match the experimental measured precursor mass. Previous DNPS methods often treat this critical information as a simple input feature or use it in post-processing, leading to numerous implausible predictions that do not adhere to this fundamental physical property. To address this limitation, we introduce DiffuNovo, a novel regressor-guided diffusion model for de novo peptide sequencing that provides explicit peptide-level mass control. Our approach integrates the mass constraint at two critical stages: during training, a novel peptide-level mass loss guides model optimization, while at inference, regressor-based guidance from gradient-based updates in the latent space steers the generation to compel the predicted peptide adheres to the mass constraint. Comprehensive evaluations on established benchmarks demonstrate that DiffuNovo surpasses state-of-the-art methods in DNPS accuracy. Additionally, as the first DNPS model to employ a diffusion model as its core backbone, DiffuNovo leverages the powerful controllability of diffusion architecture and achieves a significant reduction in mass error, thereby producing much more physically plausible peptides. These innovations represent a substantial advancement toward robust and broadly applicable DNPS. The source code is available in the supplementary material.

Predicting single-cell perturbation outcomes directly advances gene function analysis and facilitates drug candidate selection, making it a key driver of both basic and translational biomedical research. However, a major bottleneck in this task is the unpaired nature of single-cell data, as the same cell cannot be observed both before and after perturbation due to the destructive nature of sequencing. Although some neural generative transport models attempt to tackle unpaired single-cell perturbation data, they either lack explicit conditioning or depend on prior spaces for indirect distribution alignment, limiting precise perturbation modeling. In this work, we approximate Schrödinger Bridge (SB), which defines stochastic dynamic mappings recovering the entropy-regularized optimal transport (OT), to directly align the distributions of control and perturbed single-cell populations across different perturbation conditions. Unlike prior SB approximations that rely on bidirectional modeling to infer optimal source-target sample coupling, we leverage Minibatch-OT based pairing to avoid such bidirectional inference and the associated ill-posedness of defining the reverse process. This pairing directly guides bridge learning, yielding a scalable approximation to the SB. We approximate two SB models, one modeling discrete gene activation states and the other continuous expression distributions. Joint training enables accurate perturbation modeling and captures single-cell heterogeneity. Experiments on public genetic and drug perturbation datasets show that our model effectively captures heterogeneous single-cell responses and achieves state-of-the-art performance.

The advent of Large Language Models (LLMs) has fundamentally reshaped the way we interact with graphs, giving rise to a new paradigm called GraphLLM. As revealed in recent studies, graph learning can benefit from LLMs. However, we observe limited benefits when we directly utilize LLMs to make predictions for graph-related tasks within GraphLLM paradigm, which even yields suboptimal results compared to conventional GNN-based approaches. Through in-depth analysis, we find this failure can be attributed to LLMs' limited capability for processing graph data and their tendency to overlook graph information. To address this issue, we propose LoReC (Look, Remember, and Contrast), a novel plug-and-play method for GraphLLM paradigm, which enhances LLM's understanding of graph data through three stages: (1) Look: redistributing attention to graph; (2) Remember: re-injecting graph information into the Feed-Forward Network (FFN); (3) Contrast: rectifying the vanilla logits produced in the decoding process. Extensive experiments demonstrate that LoReC brings notable improvements over current GraphLLM methods and outperforms GNN-based approaches across diverse datasets. The implementation is available at https://github.com/Git-King-Zhan/LoReC.

Estimating single-cell responses across various perturbations facilitates the identification of key genes and enhances drug screening, significantly boosting experimental efficiency. However, single-cell sequencing is a destructive process, making it impossible to capture the same cell's phenotype before and after perturbation. Consequently, data collected under perturbed and unperturbed conditions are inherently unpaired, creating a critical yet unresolved problem in single-cell perturbation modeling. Moreover, the high dimensionality and sparsity of single-cell expression make direct modeling prone to focusing on zeros and neglecting meaningful patterns. To address these problems, we propose a new paradigm for single-cell perturbation modeling. Specifically, we leverage dual diffusion models to learn the control and perturbed distributions separately, and implicitly align them through a shared Gaussian latent space, without requiring explicit cell pairing. Furthermore, we introduce a sparsity masking strategy in which the mask model learns to predict zero-expressed genes, allowing the diffusion model to focus on capturing meaningful patterns among expressed genes and thereby preserving diversity in high-dimensional sparse data. We introduce \textbf{Doloris}, a generative framework that defines a new paradigm for modeling unpaired, high-dimensional, and sparse single-cell perturbation data. It leverages dual conditional diffusion models for separate learning of control and perturbed distributions, complemented by a sparsity masking strategy to enhance prediction of silent genes. The results on publicly available datasets show that our model effectively captures the diversity of single-cell perturbations and achieves state-of-the-art performance. To facilitate reproducibility, we include the code in the supplementary materials.

Graph Transformer has demonstrated impressive capabilities in the field of graph representation learning. However, existing approaches face two critical challenges: (1) most models suffer from exponentially increasing computational complexity, making it difficult to scale to large graphs; (2) attention mechanisms based on node-level operations limit the flexibility of the model and result in poor generalization performance in out-of-distribution (OOD) scenarios. To address these issues, we propose \textbf{VecFormer} (the \textbf{Vec}tor Quantized Graph Trans\textbf{former}), an efficient and highly generalizable model for node classification, particularly under OOD settings. VecFormer adopts a two-stage training paradigm. In the first stage, two codebooks are used to reconstruct the node features and the graph structure, aiming to learn the rich semantic \texttt{Graph Codes}. In the second stage, attention mechanisms are performed at the \texttt{Graph Token} level based on the transformed cross codebook, reducing computational complexity while enhancing the model's generalization capability. Extensive experiments on datasets of various sizes demonstrate that VecFormer outperforms the existing Graph Transformer in both performance and speed.

Simultaneous measurement of multiple omics modalities in single cells enables researchers to gain a more comprehensive understanding of cellular states and regulatory mechanisms. However, due to high experimental costs, significant noise, and incomplete modality coverage, a variety of computational methods for modality translation have emerged in recent years. Despite the development of translation models, there is still a lack of systematic benchmark evaluation in terms of datasets, evaluation metrics, and influencing factors. To address this, we present scTranslation, a comprehensive benchmark for single-cell multi-omics modality translation tasks. It includes diverse translation datasets, integrates state-of-the-art models, and provides a comprehensive evaluation metrics. In addition, we assess model performance under different scenarios, such as feature selection, feature quality, and few-shot settings. These factors significantly affect model performance but have rarely been systematically studied before. Leveraging this benchmark, we conduct a large-scale study of current methods, report many insightful findings that open up new possibilities for future development. The benchmark is open-sourced to facilitate future research. The code is anonymously released at https://github.com/Bunnybeibei/scTranslation.

Inferring molecular structures from infrared (IR) spectra is a fundamental yet challenging problem. A key difficulty is that an IR spectrum provides limited structural information: different molecules may share similar functional groups and local vibrational patterns, leading to highly similar spectral responses. Thus, even when an observed spectrum has a unique underlying structure, reconstructing it from the spectrum remains ambiguous. Existing IR-to-molecule models usually generate a ranked set of candidate molecules, but this set is largely determined by the model's learned generation preference and may not fully capture the structures that best satisfy the observed spectral constraints. To address this limitation, we propose SpecCal, a training-free candidate calibration framework for IR-to-molecule prediction. SpecCal operates on the candidate outputs of existing base models and improves the prediction set by re-ranking current candidates while introducing additional structurally plausible alternatives guided by spectral consistency. The framework is plug-and-play and model-agnostic, requiring no parameter updates for integration with diverse base models. Experiments on multiple benchmarks show that SpecCal consistently improves top-k reconstruction at both SMILES and scaffold levels across different base models. Further analyses demonstrate that calibrating candidate sets under spectral ambiguity provides a practical way to improve molecular reconstruction from IR spectra. The code is available at: https://anonymous.4open.science/r/SpecCal-B18A.

Molecular relational learning (MRL) seeks to understand the interaction behaviors between molecules, a pivotal task in domains such as drug discovery and materials science. Recently, extracting core substructures and modeling their interactions have emerged as mainstream approaches within machine learning-assisted methods. However, these methods still exhibit some limitations, such as insufficient consideration of molecular interactions or capturing substructures that include excessive noise, which hampers precise core substructure extraction.To address these challenges, we present an integrated dynamic framework called Iterative Substructure Extraction (ISE). ISE employs the Expectation-Maximization (EM) algorithm for MRL tasks, where the core substructures of interacting molecules are treated as latent variables and model parameters, respectively. Through iterative refinement, ISE gradually narrows the interactions from the entire molecular structures to just the core substructures.Moreover, to ensure the extracted substructures are concise and compact, we propose the Interactive Graph Information Bottleneck (IGIB) theory, which focuses on capturing the most influential yet minimal interactive substructures. In summary, our approach, guided by the IGIB theory, achieves precise substructure extraction within the ISE framework and is encapsulated in the IGIB-ISE}Extensive experiments validate the superiority of our model over state-of-the-art baselines across various tasks in terms of accuracy, generalizability, and interpretability.

Aggregating information from neighboring nodes benefits graph neural networks (GNNs) in semi-supervised node classification tasks. Nevertheless, this mechanism also renders nodes susceptible to the influence of their neighbors. For instance, this will occur when the neighboring nodes are imbalanced or the neighboring nodes contain noise, which can even affect the GNN's ability to generalize out of distribution. We find that ensuring the consistency of the norm for node representations can significantly reduce the impact of these two issues on GNNs. To this end, we propose a regularized optimization method called NodeReg that enforces the consistency of node representation norms. This method is simple but effective and satisfies Lipschitz continuity, thus facilitating stable optimization and significantly improving semi-supervised node classification performance under the above two scenarios. To illustrate, in the imbalance scenario, when training a GCN with an imbalance ratio of 0.1, NodeReg outperforms the most competitive baselines by 1.4 across five public datasets. Similarly, in the distribution shift scenario, NodeReg outperforms the most competitive baseline by 1.4