Accurately predicting cellular responses to genetic perturbations is essential for understanding disease mechanisms and designing effective therapies. Yet exhaustively exploring the space of possible perturbations (e.g., multi-gene perturbations or across tissues and cell types) is prohibitively expensive, motivating methods that can generalize to unseen conditions. In this work, we explore how knowledge graphs of gene-gene relationships can improve out-of-distribution (OOD) prediction across three challenging settings: unseen single perturbations; unseen double perturbations; and unseen cell lines. In particular, we present: (i) TxPert, a new state-of-the-art method that leverages multiple biological knowledge networks to predict transcriptional responses under OOD scenarios; (ii) an in-depth analysis demonstrating the impact of graphs, model architecture, and data on performance; and (iii) an expanded benchmarking framework that strengthens evaluation standards for perturbation modeling.
While large language models (LLMs) show great potential in temporal reasoning, most existing work focuses heavily on enhancing performance, often neglecting the explainable reasoning processes underlying the results. To address this gap, we introduce a comprehensive benchmark covering a wide range of temporal granularities, designed to systematically evaluate LLMs' capabilities in explainable temporal reasoning. Furthermore, our findings reveal that LLMs struggle to deliver convincing explanations when relying solely on textual information. To address challenge, we propose GETER, a novel structure-aware generative framework that integrates Graph structures with text for Explainable TEmporal Reasoning. Specifically, we first leverage temporal knowledge graphs to develop a temporal encoder that captures structural information for the query. Subsequently, we introduce a structure-text prefix adapter to map graph structure features into the text embedding space. Finally, LLMs generate explanation text by seamlessly integrating the soft graph token with instruction-tuning prompt tokens. Experimental results indicate that GETER achieves state-of-the-art performance while also demonstrating its effectiveness as well as strong generalization capabilities. Our dataset and code are available at https://github.com/carryTatum/GETER.
Graph-structured data pervades domains such as social networks, biological systems, knowledge graphs, and recommender systems. While foundation models have transformed natural language processing, vision, and multimodal learning through large-scale pretraining and generalization, extending these capabilities to graphs -- characterized by non-Euclidean structures and complex relational semantics -- poses unique challenges and opens new opportunities. To this end, Graph Foundation Models (GFMs) aim to bring scalable, general-purpose intelligence to structured data, enabling broad transfer across graph-centric tasks and domains. This survey provides a comprehensive overview of GFMs, unifying diverse efforts under a modular framework comprising three key components: backbone architectures, pretraining strategies, and adaptation mechanisms. We categorize GFMs by their generalization scope -- universal, task-specific, and domain-specific -- and review representative methods, key innovations, and theoretical insights within each category. Beyond methodology, we examine theoretical foundations including transferability and emergent capabilities, and highlight key challenges such as structural alignment, heterogeneity, scalability, and evaluation. Positioned at the intersection of graph learning and general-purpose AI, GFMs are poised to become foundational infrastructure for open-ended reasoning over structured data. This survey consolidates current progress and outlines future directions to guide research in this rapidly evolving field. Resources are available at https://github.com/Zehong-Wang/Awesome-Foundation-Models-on-Graphs.
Domain-specific QA systems require not just generative fluency but high factual accuracy grounded in structured expert knowledge. While recent Retrieval-Augmented Generation (RAG) frameworks improve context recall, they struggle with integrating heterogeneous data and maintaining reasoning consistency. To address these challenges, we propose DO-RAG, a scalable and customizable hybrid QA framework that integrates multi-level knowledge graph construction with semantic vector retrieval. Our system employs a novel agentic chain-of-thought architecture to extract structured relationships from unstructured, multimodal documents, constructing dynamic knowledge graphs that enhance retrieval precision. At query time, DO-RAG fuses graph and vector retrieval results to generate context-aware responses, followed by hallucination mitigation via grounded refinement. Experimental evaluations in the database and electrical domains show near-perfect recall and over 94% answer relevancy, with DO-RAG outperforming baseline frameworks by up to 33.38%. By combining traceability, adaptability, and performance efficiency, DO-RAG offers a reliable foundation for multi-domain, high-precision QA at scale.
We propose a novel framework for integrating fragmented multi-modal data in Alzheimer's disease (AD) research using large language models (LLMs) and knowledge graphs. While traditional multimodal analysis requires matched patient IDs across datasets, our approach demonstrates population-level integration of MRI, gene expression, biomarkers, EEG, and clinical indicators from independent cohorts. Statistical analysis identified significant features in each modality, which were connected as nodes in a knowledge graph. LLMs then analyzed the graph to extract potential correlations and generate hypotheses in natural language. This approach revealed several novel relationships, including a potential pathway linking metabolic risk factors to tau protein abnormalities via neuroinflammation (r>0.6, p<0.001), and unexpected correlations between frontal EEG channels and specific gene expression profiles (r=0.42-0.58, p<0.01). Cross-validation with independent datasets confirmed the robustness of major findings, with consistent effect sizes across cohorts (variance <15%). The reproducibility of these findings was further supported by expert review (Cohen's k=0.82) and computational validation. Our framework enables cross modal integration at a conceptual level without requiring patient ID matching, offering new possibilities for understanding AD pathology through fragmented data reuse and generating testable hypotheses for future research.
We introduce the concept of protoknowledge to formalize and measure how sequences of tokens encoding Knowledge Graphs are internalized during pretraining and utilized at inference time by Large Language Models (LLMs). Indeed, LLMs have demonstrated the ability to memorize vast amounts of token sequences during pretraining, and a central open question is how they leverage this memorization as reusable knowledge through generalization. We then categorize protoknowledge into lexical, hierarchical, and topological forms, varying on the type of knowledge that needs to be activated. We measure protoknowledge through Knowledge Activation Tasks (KATs), analyzing its general properties such as semantic bias. We then investigate the impact of protoknowledge on Text-to-SPARQL performance by varying prompting strategies depending on input conditions. To this end, we adopt a novel analysis framework that assesses whether model predictions align with the successful activation of the relevant protoknowledge for each query. This methodology provides a practical tool to explore Semantic-Level Data Contamination and serves as an effective strategy for Closed-Pretraining models.
Graphs serve as versatile data structures in numerous real-world domains-including social networks, molecular biology, and knowledge graphs-by capturing intricate relational information among entities. Among graph-based learning techniques, Graph Contrastive Learning (GCL) has gained significant attention for its ability to derive robust, self-supervised graph representations through the contrasting of positive and negative sample pairs. However, a critical challenge lies in ensuring high-quality positive pairs so that the intrinsic semantic and structural properties of the original graph are preserved rather than distorted. To address this issue, we propose SRGCL (Self-Reinforced Graph Contrastive Learning), a novel framework that leverages the model's own encoder to dynamically evaluate and select high-quality positive pairs. We designed a unified positive pair generator employing multiple augmentation strategies, and a selector guided by the manifold hypothesis to maintain the underlying geometry of the latent space. By adopting a probabilistic mechanism for selecting positive pairs, SRGCL iteratively refines its assessment of pair quality as the encoder's representational power improves. Extensive experiments on diverse graph-level classification tasks demonstrate that SRGCL, as a plug-in module, consistently outperforms state-of-the-art GCL methods, underscoring its adaptability and efficacy across various domains.
Large Language Models (LLMs) have inherent limitations of faithfulness and factuality, commonly referred to as hallucinations. Several benchmarks have been developed that provide a test bed for factuality evaluation within the context of English-centric datasets, while relying on supplementary informative context like web links or text passages but ignoring the available structured factual resources. To this end, Knowledge Graphs (KGs) have been identified as a useful aid for hallucination mitigation, as they provide a structured way to represent the facts about entities and their relations with minimal linguistic overhead. We bridge the lack of KG paths and multilinguality for factual language modeling within the existing hallucination evaluation benchmarks and propose a KG-based multilingual, multihop benchmark called \textbf{MultiHal} framed for generative text evaluation. As part of our data collection pipeline, we mined 140k KG-paths from open-domain KGs, from which we pruned noisy KG-paths, curating a high-quality subset of 25.9k. Our baseline evaluation shows an absolute scale increase by approximately 0.12 to 0.36 points for the semantic similarity score in KG-RAG over vanilla QA across multiple languages and multiple models, demonstrating the potential of KG integration. We anticipate MultiHal will foster future research towards several graph-based hallucination mitigation and fact-checking tasks.
Recent advances in large language models (LLMs) and the abundance of food data have resulted in studies to improve food understanding using LLMs. Despite several recommendation systems utilizing LLMs and Knowledge Graphs (KGs), there has been limited research on integrating food related KGs with LLMs. We introduce KERL, a unified system that leverages food KGs and LLMs to provide personalized food recommendations and generates recipes with associated micro-nutritional information. Given a natural language question, KERL extracts entities, retrieves subgraphs from the KG, which are then fed into the LLM as context to select the recipes that satisfy the constraints. Next, our system generates the cooking steps and nutritional information for each recipe. To evaluate our approach, we also develop a benchmark dataset by curating recipe related questions, combined with constraints and personal preferences. Through extensive experiments, we show that our proposed KG-augmented LLM significantly outperforms existing approaches, offering a complete and coherent solution for food recommendation, recipe generation, and nutritional analysis. Our code and benchmark datasets are publicly available at https://github.com/mohbattharani/KERL.
Temporal Knowledge Graphs (TKGs), as an extension of static Knowledge Graphs (KGs), incorporate the temporal feature to express the transience of knowledge by describing when facts occur. TKG extrapolation aims to infer possible future facts based on known history, which has garnered significant attention in recent years. Some existing methods treat TKG as a sequence of independent subgraphs to model temporal evolution patterns, demonstrating impressive reasoning performance. However, they still have limitations: 1) In modeling subgraph semantic evolution, they usually neglect the internal structural interactions between subgraphs, which are actually crucial for encoding TKGs. 2) They overlook the potential smooth features that do not lead to semantic changes, which should be distinguished from the semantic evolution process. Therefore, we propose a novel Disentangled Multi-span Evolutionary Network (DiMNet) for TKG reasoning. Specifically, we design a multi-span evolution strategy that captures local neighbor features while perceiving historical neighbor semantic information, thus enabling internal interactions between subgraphs during the evolution process. To maximize the capture of semantic change patterns, we design a disentangle component that adaptively separates nodes' active and stable features, used to dynamically control the influence of historical semantics on future evolution. Extensive experiments conducted on four real-world TKG datasets show that DiMNet demonstrates substantial performance in TKG reasoning, and outperforms the state-of-the-art up to 22.7% in MRR.
Finding interesting phenomena is the core of scientific discovery, but it is a manual, ill-defined concept. We present an integrative pipeline for automating the discovery of interesting simple hypotheses (feature-target relations with effect direction and a potential underlying mechanism) in structured biomedical data. The pipeline combines machine learning, knowledge graphs, literature search and Large Language Models. We formalize "interestingness" as a combination of novelty, utility and plausibility. On 8 major diseases from the UK Biobank, our pipeline consistently recovers risk factors years before their appearance in the literature. 40--53% of our top candidates were validated as interesting, compared to 0--7% for a SHAP-based baseline. Overall, 28% of 109 candidates were interesting to medical experts. The pipeline addresses the challenge of operationalizing "interestingness" scalably and for any target. We release data and code: https://github.com/LinialLab/InterFeat
Retrieval-Augmented Generation (RAG) systems empower large language models (LLMs) with external knowledge, yet struggle with efficiency-accuracy trade-offs when scaling to large knowledge graphs. Existing approaches often rely on monolithic graph retrieval, incurring unnecessary latency for simple queries and fragmented reasoning for complex multi-hop questions. To address these challenges, this paper propose SPLIT-RAG, a multi-agent RAG framework that addresses these limitations with question-driven semantic graph partitioning and collaborative subgraph retrieval. The innovative framework first create Semantic Partitioning of Linked Information, then use the Type-Specialized knowledge base to achieve Multi-Agent RAG. The attribute-aware graph segmentation manages to divide knowledge graphs into semantically coherent subgraphs, ensuring subgraphs align with different query types, while lightweight LLM agents are assigned to partitioned subgraphs, and only relevant partitions are activated during retrieval, thus reduce search space while enhancing efficiency. Finally, a hierarchical merging module resolves inconsistencies across subgraph-derived answers through logical verifications. Extensive experimental validation demonstrates considerable improvements compared to existing approaches.
Knowledge graphs (KGs) have become an effective paradigm for managing real-world facts, which are not only complex but also dynamically evolve over time. The temporal validity of facts often serves as a strong clue in downstream link prediction tasks, which predicts a missing element in a fact. Traditional link prediction techniques on temporal KGs either consider a sequence of temporal snapshots of KGs with an ad-hoc defined time interval or expand a temporal fact over its validity period under a predefined time granularity; these approaches not only suffer from the sensitivity of the selection of time interval/granularity, but also face the computational challenges when handling facts with long (even infinite) validity. Although the recent hyper-relational KGs represent the temporal validity of a fact as qualifiers describing the fact, it is still suboptimal due to its ignorance of the infinite validity of some facts and the insufficient information encoded from the qualifiers about the temporal validity. Against this background, we propose VITA, a $\underline{V}$ersatile t$\underline{I}$me represen$\underline{TA}$tion learning method for temporal hyper-relational knowledge graphs. We first propose a versatile time representation that can flexibly accommodate all four types of temporal validity of facts (i.e., since, until, period, time-invariant), and then design VITA to effectively learn the time information in both aspects of time value and timespan to boost the link prediction performance. We conduct a thorough evaluation of VITA compared to a sizable collection of baselines on real-world KG datasets. Results show that VITA outperforms the best-performing baselines in various link prediction tasks (predicting missing entities, relations, time, and other numeric literals) by up to 75.3%. Ablation studies and a case study also support our key design choices.
The SPARQL query language is the standard method to access knowledge graphs (KGs). However, formulating SPARQL queries is a significant challenge for non-expert users, and remains time-consuming for the experienced ones. Best practices recommend to document KGs with competency questions and example queries to contextualise the knowledge they contain and illustrate their potential applications. In practice, however, this is either not the case or the examples are provided in limited numbers. Large Language Models (LLMs) are being used in conversational agents and are proving to be an attractive solution with a wide range of applications, from simple question-answering about common knowledge to generating code in a targeted programming language. However, training and testing these models to produce high quality SPARQL queries from natural language questions requires substantial datasets of question-query pairs. In this paper, we present Q${}^2$Forge that addresses the challenge of generating new competency questions for a KG and corresponding SPARQL queries. It iteratively validates those queries with human feedback and LLM as a judge. Q${}^2$Forge is open source, generic, extensible and modular, meaning that the different modules of the application (CQ generation, query generation and query refinement) can be used separately, as an integrated pipeline, or replaced by alternative services. The result is a complete pipeline from competency question formulation to query evaluation, supporting the creation of reference query sets for any target KG.
This demo paper reports on a new workflow \textit{GhostWriter} that combines the use of Large Language Models and Knowledge Graphs (semantic artifacts) to support navigation through collections. Situated in the research area of Retrieval Augmented Generation, this specific workflow represents the creation of local and adaptable chatbots. Based on the tool-suite \textit{EverythingData} at the backend, \textit{GhostWriter} provides an interface that enables querying and ``chatting'' with a collection. Applied iteratively, the workflow supports the information needs of researchers when interacting with a collection of papers, whether it be to gain an overview, to learn more about a specific concept and its context, and helps the researcher ultimately to refine their research question in a controlled way. We demonstrate the workflow for a collection of articles from the \textit{method data analysis} journal published by GESIS -- Leibniz-Institute for the Social Sciences. We also point to further application areas.
Model editing aims to enhance the accuracy and reliability of large language models (LLMs) by efficiently adjusting their internal parameters. Currently, most LLM editing datasets are confined to narrow knowledge domains and cover a limited range of editing evaluation. They often overlook the broad scope of editing demands and the diversity of ripple effects resulting from edits. In this context, we introduce UniEdit, a unified benchmark for LLM editing grounded in open-domain knowledge. First, we construct editing samples by selecting entities from 25 common domains across five major categories, utilizing the extensive triple knowledge available in open-domain knowledge graphs to ensure comprehensive coverage of the knowledge domains. To address the issues of generality and locality in editing, we design an Neighborhood Multi-hop Chain Sampling (NMCS) algorithm to sample subgraphs based on a given knowledge piece to entail comprehensive ripple effects to evaluate. Finally, we employ proprietary LLMs to convert the sampled knowledge subgraphs into natural language text, guaranteeing grammatical accuracy and syntactical diversity. Extensive statistical analysis confirms the scale, comprehensiveness, and diversity of our UniEdit benchmark. We conduct comprehensive experiments across multiple LLMs and editors, analyzing their performance to highlight strengths and weaknesses in editing across open knowledge domains and various evaluation criteria, thereby offering valuable insights for future research endeavors.
Taxonomies are hierarchical knowledge graphs crucial for recommendation systems, and web applications. As data grows, expanding taxonomies is essential, but existing methods face key challenges: (1) discriminative models struggle with representation limits and generalization, while (2) generative methods either process all candidates at once, introducing noise and exceeding context limits, or discard relevant entities by selecting noisy candidates. We propose LORex ($\textbf{L}$ineage-$\textbf{O}$riented $\textbf{Re}$asoning for Taxonomy E$\textbf{x}$pansion), a plug-and-play framework that combines discriminative ranking and generative reasoning for efficient taxonomy expansion. Unlike prior methods, LORex ranks and chunks candidate terms into batches, filtering noise and iteratively refining selections by reasoning candidates' hierarchy to ensure contextual efficiency. Extensive experiments across four benchmarks and twelve baselines show that LORex improves accuracy by 12% and Wu & Palmer similarity by 5% over state-of-the-art methods.
Medication recommendations have become an important task in the healthcare domain, especially in measuring the accuracy and safety of medical dialogue systems (MDS). Different from the recommendation task based on electronic health records (EHRs), dialogue-based medication recommendations require research on the interaction details between patients and doctors, which is crucial but may not exist in EHRs. Recent advancements in large language models (LLM) have extended the medical dialogue domain. These LLMs can interpret patients' intent and provide medical suggestions including medication recommendations, but some challenges are still worth attention. During a multi-turn dialogue, LLMs may ignore the fine-grained medical information or connections across the dialogue turns, which is vital for providing accurate suggestions. Besides, LLMs may generate non-factual responses when there is a lack of domain-specific knowledge, which is more risky in the medical domain. To address these challenges, we propose a \textbf{G}raph-\textbf{A}ssisted \textbf{P}rompts (\textbf{GAP}) framework for dialogue-based medication recommendation. It extracts medical concepts and corresponding states from dialogue to construct an explicitly patient-centric graph, which can describe the neglected but important information. Further, combined with external medical knowledge graphs, GAP can generate abundant queries and prompts, thus retrieving information from multiple sources to reduce the non-factual responses. We evaluate GAP on a dialogue-based medication recommendation dataset and further explore its potential in a more difficult scenario, dynamically diagnostic interviewing. Extensive experiments demonstrate its competitive performance when compared with strong baselines.
Recently, large language models (LLMs) have demonstrated impressive performance in Knowledge Graph Question Answering (KGQA) tasks, which aim to find answers based on knowledge graphs (KGs) for natural language questions. Existing LLMs-based KGQA methods typically follow the Graph Retrieval-Augmented Generation (GraphRAG) paradigm, which first retrieves reasoning paths from the large KGs, and then generates the answers based on them. However, these methods emphasize the exploration of new optimal reasoning paths in KGs while ignoring the exploitation of historical reasoning paths, which may lead to sub-optimal reasoning paths. Additionally, the complex semantics contained in questions may lead to the retrieval of inaccurate reasoning paths. To address these issues, this paper proposes a novel and training-free framework for KGQA tasks called Reward-guided Tree Search on Graph (RTSoG). RTSoG decomposes an original question into a series of simpler and well-defined sub-questions to handle the complex semantics. Then, a Self-Critic Monte Carlo Tree Search (SC-MCTS) guided by a reward model is introduced to iteratively retrieve weighted reasoning paths as contextual knowledge. Finally, it stacks the weighted reasoning paths according to their weights to generate the final answers. Extensive experiments on four datasets demonstrate the effectiveness of RTSoG. Notably, it achieves 8.7\% and 7.0\% performance improvement over the state-of-the-art method on the GrailQA and the WebQSP respectively.
Hierarchical data arise in countless domains, from biological taxonomies and organizational charts to legal codes and knowledge graphs. Residual Quantization (RQ) is widely used to generate discrete, multitoken representations for such data by iteratively quantizing residuals in a multilevel codebook. However, its reliance on Euclidean geometry can introduce fundamental mismatches that hinder modeling of hierarchical branching, necessary for faithful representation of hierarchical data. In this work, we propose Hyperbolic Residual Quantization (HRQ), which embeds data natively in a hyperbolic manifold and performs residual quantization using hyperbolic operations and distance metrics. By adapting the embedding network, residual computation, and distance metric to hyperbolic geometry, HRQ imparts an inductive bias that aligns naturally with hierarchical branching. We claim that HRQ in comparison to RQ can generate more useful for downstream tasks discrete hierarchical representations for data with latent hierarchies. We evaluate HRQ on two tasks: supervised hierarchy modeling using WordNet hypernym trees, where the model is supervised to learn the latent hierarchy - and hierarchy discovery, where, while latent hierarchy exists in the data, the model is not directly trained or evaluated on a task related to the hierarchy. Across both scenarios, HRQ hierarchical tokens yield better performance on downstream tasks compared to Euclidean RQ with gains of up to $20\%$ for the hierarchy modeling task. Our results demonstrate that integrating hyperbolic geometry into discrete representation learning substantially enhances the ability to capture latent hierarchies.