Daily Papers

Protein language models are a powerful tool for learning protein representations through pre-training on vast protein sequence datasets. However, traditional protein language models lack explicit structural supervision, despite its relevance to protein function. To address this issue, we introduce the integration of remote homology detection to distill structural information into protein language models without requiring explicit protein structures as input. We evaluate the impact of this structure-informed training on downstream protein function prediction tasks. Experimental results reveal consistent improvements in function annotation accuracy for EC number and GO term prediction. Performance on mutant datasets, however, varies based on the relationship between targeted properties and protein structures. This underscores the importance of considering this relationship when applying structure-aware training to protein function prediction tasks. Code and model weights are available at https://github.com/DeepGraphLearning/esm-s.

Persistent homology (PH) provides topological descriptors for geometric data, such as weighted graphs, which are interpretable, stable to perturbations, and invariant under, e.g., relabeling. Most applications of PH focus on the one-parameter case -- where the descriptors summarize the changes in topology of data as it is filtered by a single quantity of interest -- and there is now a wide array of methods enabling the use of one-parameter PH descriptors in data science, which rely on the stable vectorization of these descriptors as elements of a Hilbert space. Although the multiparameter PH (MPH) of data that is filtered by several quantities of interest encodes much richer information than its one-parameter counterpart, the scarceness of stability results for MPH descriptors has so far limited the available options for the stable vectorization of MPH. In this paper, we aim to bring together the best of both worlds by showing how the interpretation of signed barcodes -- a recent family of MPH descriptors -- as signed measures leads to natural extensions of vectorization strategies from one parameter to multiple parameters. The resulting feature vectors are easy to define and to compute, and provably stable. While, as a proof of concept, we focus on simple choices of signed barcodes and vectorizations, we already see notable performance improvements when comparing our feature vectors to state-of-the-art topology-based methods on various types of data.

Real-valued functions on geometric data -- such as node attributes on a graph -- can be optimized using descriptors from persistent homology, allowing the user to incorporate topological terms in the loss function. When optimizing a single real-valued function (the one-parameter setting), there is a canonical choice of descriptor for persistent homology: the barcode. The operation mapping a real-valued function to its barcode is differentiable almost everywhere, and the convergence of gradient descent for losses using barcodes is relatively well understood. When optimizing a vector-valued function (the multiparameter setting), there is no unique choice of descriptor for multiparameter persistent homology, and many distinct descriptors have been proposed. This calls for the development of a general framework for differentiability and optimization that applies to a wide range of multiparameter homological descriptors. In this article, we develop such a framework and show that it encompasses well-known descriptors of different flavors, such as signed barcodes and the multiparameter persistence landscape. We complement the theory with numerical experiments supporting the idea that optimizing multiparameter homological descriptors can lead to improved performances compared to optimizing one-parameter descriptors, even when using the simplest and most efficiently computable multiparameter descriptors.

Persistent homology, a technique from computational topology, has recently shown strong empirical performance in the context of graph classification. Being able to capture long range graph properties via higher-order topological features, such as cycles of arbitrary length, in combination with multi-scale topological descriptors, has improved predictive performance for data sets with prominent topological structures, such as molecules. At the same time, the theoretical properties of persistent homology have not been formally assessed in this context. This paper intends to bridge the gap between computational topology and graph machine learning by providing a brief introduction to persistent homology in the context of graphs, as well as a theoretical discussion and empirical analysis of its expressivity for graph learning tasks.

Topological data analysis (TDA) is an area of data science that focuses on using invariants from algebraic topology to provide multiscale shape descriptors for geometric data sets such as point clouds. One of the most important such descriptors is {\em persistent homology}, which encodes the change in shape as a filtration parameter changes; a typical parameter is the feature scale. For many data sets, it is useful to simultaneously vary multiple filtration parameters, for example feature scale and density. While the theoretical properties of single parameter persistent homology are well understood, less is known about the multiparameter case. In particular, a central question is the problem of representing multiparameter persistent homology by elements of a vector space for integration with standard machine learning algorithms. Existing approaches to this problem either ignore most of the multiparameter information to reduce to the one-parameter case or are heuristic and potentially unstable in the face of noise. In this article, we introduce a new general representation framework that leverages recent results on {\em decompositions} of multiparameter persistent homology. This framework is rich in information, fast to compute, and encompasses previous approaches. Moreover, we establish theoretical stability guarantees under this framework as well as efficient algorithms for practical computation, making this framework an applicable and versatile tool for analyzing geometric and point cloud data. We validate our stability results and algorithms with numerical experiments that demonstrate statistical convergence, prediction accuracy, and fast running times on several real data sets.

In recent years, persistent homology (PH) has been successfully applied to real-world data in many different settings. Despite significant computational advances, PH algorithms do not yet scale to large datasets preventing interesting applications. One approach to address computational issues posed by PH is to select a set of landmarks by subsampling from the data. Currently, these landmark points are chosen either at random or using the maxmin algorithm. Neither is ideal as random selection tends to favour dense areas of the data while the maxmin algorithm is very sensitive to noise. Here, we propose a novel approach to select landmarks specifically for PH that preserves coarse topological information of the original dataset. Our method is motivated by the Mayer-Vietoris sequence and requires only local PH computation thus enabling efficient computation. We test our landmarks on artificial datasets which contain different levels of noise and compare them to standard landmark selection techniques. We demonstrate that our landmark selection outperforms standard methods as well as a subsampling technique based on an outlier-robust version of the k--means algorithm for low sampling densities in noisy data with respect to robustness to outliers.

The automated analysis of chemical literature holds promise to accelerate discovery in fields such as material science and drug development. In particular, search capabilities for chemical structures and Markush structures (chemical structure templates) within patent documents are valuable, e.g., for prior-art search. Advancements have been made in the automatic extraction of chemical structures from text and images, yet the Markush structures remain largely unexplored due to their complex multi-modal nature. In this work, we present MarkushGrapher, a multi-modal approach for recognizing Markush structures in documents. Our method jointly encodes text, image, and layout information through a Vision-Text-Layout encoder and an Optical Chemical Structure Recognition vision encoder. These representations are merged and used to auto-regressively generate a sequential graph representation of the Markush structure along with a table defining its variable groups. To overcome the lack of real-world training data, we propose a synthetic data generation pipeline that produces a wide range of realistic Markush structures. Additionally, we present M2S, the first annotated benchmark of real-world Markush structures, to advance research on this challenging task. Extensive experiments demonstrate that our approach outperforms state-of-the-art chemistry-specific and general-purpose vision-language models in most evaluation settings. Code, models, and datasets will be available.

DNA sequence alignment involves assigning short DNA reads to the most probable locations on an extensive reference genome. This process is crucial for various genomic analyses, including variant calling, transcriptomics, and epigenomics. Conventional methods, refined over decades, tackle this challenge in 2 steps: genome indexing followed by efficient search to locate likely positions for given reads. Building on the success of Large Language Models in encoding text into embeddings, where the distance metric captures semantic similarity, recent efforts have explored whether the same Transformer architecture can produce embeddings for DNA sequences. Such models have shown early promise in classifying short DNA sequences, such as detecting coding/non-coding regions, and enhancer, promoter sequences. However, performance at sequence classification tasks does not translate to sequence alignment, where it is necessary to search across the genome to align each read, a significantly longer-range task. We bridge this gap by framing the Sequence Alignment task for Transformer models as an "Embed-Search-Align" task. In this framework, a novel Reference-Free DNA Embedding model generates embeddings of reads and reference fragments, which are projected into a shared vector space where the read-fragment distance is used as a surrogate for alignment. Technical contributions include: (1) Contrastive loss for self-supervised training of DNA sequence representations, facilitating rich reference-free, sequence-level embeddings, and (2) a DNA vector store to enable search across fragments on a global scale. DNA-ESA is 99% accurate when aligning 250-length reads onto a human genome (3gb), rivaling conventional methods such as Bowtie and BWA-Mem. DNA-ESA exceeds the performance of 6 Transformer model baselines such as Nucleotide Transformer, Hyena-DNA, and shows task transfer across chromosomes and species.

With the increasing prevalence of graph-structured data, multi-view graph clustering has been widely used in various downstream applications. Existing approaches primarily rely on a unified message passing mechanism, which significantly enhances clustering performance. Nevertheless, this mechanism limits its applicability to heterophilous situations, as it is fundamentally predicated on the assumption of homophily, i.e., the connected nodes often belong to the same class. In reality, this assumption does not always hold; a moderately or even mildly homophilous graph is more common than a fully homophilous one due to inevitable heterophilous information in the graph. To address this issue, in this paper, we propose a novel SiMilarity-enhanced Homophily for Multi-view Heterophilous Graph Clustering (SMHGC) approach. By analyzing the relationship between similarity and graph homophily, we propose to enhance the homophily by introducing three similarity terms, i.e., neighbor pattern similarity, node feature similarity, and multi-view global similarity, in a label-free manner. Then, a consensus-based inter- and intra-view fusion paradigm is proposed to fuse the improved homophilous graph from different views and utilize them for clustering. The state-of-the-art experimental results on both multi-view heterophilous and homophilous datasets collectively demonstrate the strong capacity of similarity for unsupervised multi-view heterophilous graph learning. Additionally, the consistent performance across semi-synthetic datasets with varying levels of homophily serves as further evidence of SMHGC's resilience to heterophily.

The structure of topology underpins much of the research on performance and robustness, yet available topology data are typically scarce, necessitating the generation of synthetic graphs with desired properties for testing or release. Prior diffusion-based approaches either embed conditions into the diffusion model, requiring retraining for each attribute and hindering real-time applicability, or use classifier-based guidance post-training, which does not account for topology scale and practical constraints. In this paper, we show from a discrete perspective that gradients from a pre-trained graph-level classifier can be incorporated into the discrete reverse diffusion posterior to steer generation toward specified structural properties. Based on this insight, we propose Classifier-guided Conditional Topology Generation with Persistent Homology (CoPHo), which builds a persistent homology filtration over intermediate graphs and interprets features as guidance signals that steer generation toward the desired properties at each denoising step. Experiments on four generic/network datasets demonstrate that CoPHo outperforms existing methods at matching target metrics, and we further validate its transferability on the QM9 molecular dataset.

The field of bioinformatics has seen significant progress, making the cross-modal text-molecule retrieval task increasingly vital. This task focuses on accurately retrieving molecule structures based on textual descriptions, by effectively aligning textual descriptions and molecules to assist researchers in identifying suitable molecular candidates. However, many existing approaches overlook the details inherent in molecule sub-structures. In this work, we introduce the Optimal TRansport-based Multi-grained Alignments model (ORMA), a novel approach that facilitates multi-grained alignments between textual descriptions and molecules. Our model features a text encoder and a molecule encoder. The text encoder processes textual descriptions to generate both token-level and sentence-level representations, while molecules are modeled as hierarchical heterogeneous graphs, encompassing atom, motif, and molecule nodes to extract representations at these three levels. A key innovation in ORMA is the application of Optimal Transport (OT) to align tokens with motifs, creating multi-token representations that integrate multiple token alignments with their corresponding motifs. Additionally, we employ contrastive learning to refine cross-modal alignments at three distinct scales: token-atom, multitoken-motif, and sentence-molecule, ensuring that the similarities between correctly matched text-molecule pairs are maximized while those of unmatched pairs are minimized. To our knowledge, this is the first attempt to explore alignments at both the motif and multi-token levels. Experimental results on the ChEBI-20 and PCdes datasets demonstrate that ORMA significantly outperforms existing state-of-the-art (SOTA) models.

Machine learning for point clouds has been attracting much attention, with many applications in various fields, such as shape recognition and material science. For enhancing the accuracy of such machine learning methods, it is often effective to incorporate global topological features, which are typically extracted by persistent homology. In the calculation of persistent homology for a point cloud, we choose a filtration for the point cloud, an increasing sequence of spaces. Since the performance of machine learning methods combined with persistent homology is highly affected by the choice of a filtration, we need to tune it depending on data and tasks. In this paper, we propose a framework that learns a filtration adaptively with the use of neural networks. In order to make the resulting persistent homology isometry-invariant, we develop a neural network architecture with such invariance. Additionally, we show a theoretical result on a finite-dimensional approximation of filtration functions, which justifies the proposed network architecture. Experimental results demonstrated the efficacy of our framework in several classification tasks.

Storing information in DNA molecules is of great interest because of its advantages in longevity, high storage density, and low maintenance cost. A key step in the DNA storage pipeline is to efficiently cluster the retrieved DNA sequences according to their similarities. Levenshtein distance is the most suitable metric on the similarity between two DNA sequences, but it is inferior in terms of computational complexity and less compatible with mature clustering algorithms. In this work, we propose a novel deep squared Euclidean embedding for DNA sequences using Siamese neural network, squared Euclidean embedding, and chi-squared regression. The Levenshtein distance is approximated by the squared Euclidean distance between the embedding vectors, which is fast calculated and clustering algorithm friendly. The proposed approach is analyzed theoretically and experimentally. The results show that the proposed embedding is efficient and robust.

The rapid expansion of genomic sequence data calls for new methods to achieve robust sequence representations. Existing techniques often neglect intricate structural details, emphasizing mainly contextual information. To address this, we developed k-mer embeddings that merge contextual and structural string information by enhancing De Bruijn graphs with structural similarity connections. Subsequently, we crafted a self-supervised method based on Contrastive Learning that employs a heterogeneous Graph Convolutional Network encoder and constructs positive pairs based on node similarities. Our embeddings consistently outperform prior techniques for Edit Distance Approximation and Closest String Retrieval tasks.

A suitable feature representation that can both preserve the data intrinsic information and reduce data complexity and dimensionality is key to the performance of machine learning models. Deeply rooted in algebraic topology, persistent homology (PH) provides a delicate balance between data simplification and intrinsic structure characterization, and has been applied to various areas successfully. However, the combination of PH and machine learning has been hindered greatly by three challenges, namely topological representation of data, PH-based distance measurements or metrics, and PH-based feature representation. With the development of topological data analysis, progresses have been made on all these three problems, but widely scattered in different literatures. In this paper, we provide a systematical review of PH and PH-based supervised and unsupervised models from a computational perspective. Our emphasizes are the recent development of mathematical models and tools, including PH softwares and PH-based functions, feature representations, kernels, and similarity models. Essentially, this paper can work as a roadmap for the practical application of PH-based machine learning tools. Further, we consider different topological feature representations in different machine learning models, and investigate their impacts on the protein secondary structure classification.

We present Connection-Aware Motif Sequencing (CamS), a graph-to-sequence representation that enables decoder-only Transformers to learn molecular graphs via standard next-token prediction (NTP). For molecular property prediction, SMILES-based NTP scales well but lacks explicit topology, whereas graph-native masked modeling captures connectivity but risks disrupting the pivotal chemical details (e.g., activity cliffs). CamS bridges this gap by serializing molecular graphs into structure-rich causal sequences. CamS first mines data-driven connection-aware motifs. It then serializes motifs via scaffold-rooted breadth-first search (BFS) to establish a stable core-to-periphery order. Crucially, CamS enables hierarchical modeling by concatenating sequences from fine to coarse motif scales, allowing the model to condition global scaffolds on dense, uncorrupted local structural evidence. We instantiate CamS-LLaMA by pre-training a vanilla LLaMA backbone on CamS sequences. It achieves state-of-the-art performance on MoleculeNet and the activity-cliff benchmark MoleculeACE, outperforming both SMILES-based language models and strong graph baselines. Interpretability analysis confirms that our multi-scale causal serialization effectively drives attention toward cliff-determining differences.

Large language models (LLMs) are increasingly recognized as powerful tools for scientific discovery, particularly in molecular science. A fundamental requirement for these models is the ability to accurately understand molecular structures, commonly encoded in the SMILES representation. However, current LLMs struggle to interpret SMILES, even failing to carry out basic tasks such as counting molecular rings. To address this limitation, we introduce CLEANMOL, a novel framework that formulates SMILES parsing into a suite of clean and deterministic tasks explicitly designed to promote graph-level molecular comprehension. These tasks span from subgraph matching to global graph matching, providing structured supervision aligned with molecular structural properties. We construct a molecular pretraining dataset with adaptive difficulty scoring and pre-train open-source LLMs on these tasks. Our results show that CLEANMOL not only enhances structural comprehension but also achieves the best or competes with the baseline on the Mol-Instructions benchmark.

Vector similarity search presents significant challenges in terms of scalability for large and high-dimensional datasets, as well as in providing native support for hybrid queries. Serverless computing and cloud functions offer attractive benefits such as elasticity and cost-effectiveness, but are difficult to apply to data-intensive workloads. Jointly addressing these two main challenges, we present SQUASH, the first fully serverless vector search solution with rich support for hybrid queries. It features OSQ, an optimized and highly parallelizable quantization-based approach for vectors and attributes. Its segment-based storage mechanism enables significant compression in resource-constrained settings and offers efficient dimensional extraction operations. SQUASH performs a single distributed pass to guarantee the return of sufficiently many vectors satisfying the filter predicate, achieving high accuracy and avoiding redundant computation for vectors which fail the predicate. A multi-level search workflow is introduced to prune most vectors early to minimize the load on Function-as-a-Service (FaaS) instances. SQUASH is designed to identify and utilize retention of relevant data in re-used runtime containers, which eliminates redundant I/O and reduces costs. Finally, we demonstrate a new tree-based method for rapid FaaS invocation, enabling the bi-directional flow of data via request/response payloads. Experiments comparing SQUASH with state-of-the-art serverless vector search solutions and server-based baselines on vector search benchmarks confirm significant performance improvements at a lower cost.

The development of data-dependent heuristics and representations for biological sequences that reflect their evolutionary distance is critical for large-scale biological research. However, popular machine learning approaches, based on continuous Euclidean spaces, have struggled with the discrete combinatorial formulation of the edit distance that models evolution and the hierarchical relationship that characterises real-world datasets. We present Neural Distance Embeddings (NeuroSEED), a general framework to embed sequences in geometric vector spaces, and illustrate the effectiveness of the hyperbolic space that captures the hierarchical structure and provides an average 22% reduction in embedding RMSE against the best competing geometry. The capacity of the framework and the significance of these improvements are then demonstrated devising supervised and unsupervised NeuroSEED approaches to multiple core tasks in bioinformatics. Benchmarked with common baselines, the proposed approaches display significant accuracy and/or runtime improvements on real-world datasets. As an example for hierarchical clustering, the proposed pretrained and from-scratch methods match the quality of competing baselines with 30x and 15x runtime reduction, respectively.

Link prediction, a fundamental task on graphs, has proven indispensable in various applications, e.g., friend recommendation, protein analysis, and drug interaction prediction. However, since datasets span a multitude of domains, they could have distinct underlying mechanisms of link formation. Evidence in existing literature underscores the absence of a universally best algorithm suitable for all datasets. In this paper, we endeavor to explore principles of link prediction across diverse datasets from a data-centric perspective. We recognize three fundamental factors critical to link prediction: local structural proximity, global structural proximity, and feature proximity. We then unearth relationships among those factors where (i) global structural proximity only shows effectiveness when local structural proximity is deficient. (ii) The incompatibility can be found between feature and structural proximity. Such incompatibility leads to GNNs for Link Prediction (GNN4LP) consistently underperforming on edges where the feature proximity factor dominates. Inspired by these new insights from a data perspective, we offer practical instruction for GNN4LP model design and guidelines for selecting appropriate benchmark datasets for more comprehensive evaluations.

Modern representation learning increasingly relies on unsupervised and self-supervised methods trained on large-scale unlabeled data. While these approaches achieve impressive generalization across tasks and domains, evaluating embedding quality without labels remains an open challenge. In this work, we propose Persistence, a topology-aware metric based on persistent homology that quantifies the geometric structure and topological richness of embedding spaces in a fully unsupervised manner. Unlike metrics that assume linear separability or rely on covariance structure, Persistence captures global and multi-scale organization. Empirical results across diverse domains show that Persistence consistently achieves top-tier correlations with downstream performance, outperforming existing unsupervised metrics and enabling reliable model and hyperparameter selection.

Clustering aims to group unlabelled samples based on their similarities. It has become a significant tool for the analysis of high-dimensional data. However, most of the clustering methods merely generate pseudo labels and thus are unable to simultaneously present the similarities between different clusters and outliers. This paper proposes a new framework called High-dimensional Clustering onto Hamiltonian Cycle (HCHC) to solve the above problems. First, HCHC combines global structure with local structure in one objective function for deep clustering, improving the labels as relative probabilities, to mine the similarities between different clusters while keeping the local structure in each cluster. Then, the anchors of different clusters are sorted on the optimal Hamiltonian cycle generated by the cluster similarities and mapped on the circumference of a circle. Finally, a sample with a higher probability of a cluster will be mapped closer to the corresponding anchor. In this way, our framework allows us to appreciate three aspects visually and simultaneously - clusters (formed by samples with high probabilities), cluster similarities (represented as circular distances), and outliers (recognized as dots far away from all clusters). The experiments illustrate the superiority of HCHC.

As part of an ongoing worldwide effort to comprehend and monitor insect biodiversity, this paper presents the BIOSCAN-5M Insect dataset to the machine learning community and establish several benchmark tasks. BIOSCAN-5M is a comprehensive dataset containing multi-modal information for over 5 million insect specimens, and it significantly expands existing image-based biological datasets by including taxonomic labels, raw nucleotide barcode sequences, assigned barcode index numbers, and geographical information. We propose three benchmark experiments to demonstrate the impact of the multi-modal data types on the classification and clustering accuracy. First, we pretrain a masked language model on the DNA barcode sequences of the BIOSCAN-5M dataset, and demonstrate the impact of using this large reference library on species- and genus-level classification performance. Second, we propose a zero-shot transfer learning task applied to images and DNA barcodes to cluster feature embeddings obtained from self-supervised learning, to investigate whether meaningful clusters can be derived from these representation embeddings. Third, we benchmark multi-modality by performing contrastive learning on DNA barcodes, image data, and taxonomic information. This yields a general shared embedding space enabling taxonomic classification using multiple types of information and modalities. The code repository of the BIOSCAN-5M Insect dataset is available at {https://github.com/zahrag/BIOSCAN-5M}

We study the implications of the modeling choice to use a graph, instead of a hypergraph, to represent real-world interconnected systems whose constituent relationships are of higher order by nature. Such a modeling choice typically involves an underlying projection process that maps the original hypergraph onto a graph, and is common in graph-based analysis. While hypergraph projection can potentially lead to loss of higher-order relations, there exists very limited studies on the consequences of doing so, as well as its remediation. This work fills this gap by doing two things: (1) we develop analysis based on graph and set theory, showing two ubiquitous patterns of hyperedges that are root to structural information loss in all hypergraph projections; we also quantify the combinatorial impossibility of recovering the lost higher-order structures if no extra help is provided; (2) we still seek to recover the lost higher-order structures in hypergraph projection, and in light of (1)'s findings we propose to relax the problem into a learning-based setting. Under this setting, we develop a learning-based hypergraph reconstruction method based on an important statistic of hyperedge distributions that we find. Our reconstruction method is evaluated on 8 real-world datasets under different settings, and exhibits consistently good performance. We also demonstrate benefits of the reconstructed hypergraphs via use cases of protein rankings and link predictions.

In contrast to their remarkable performance on general knowledge QA, the true abilities of Large Language Models (LLMs) in tasks demanding deep, specialized reasoning, such as in protein biology, have yet to be thoroughly investigated. Current benchmarks suffer from critical deficiencies, such as data contamination due to outdated test sets, insufficient focus on essential protein-specific tasks, and a neglect of multimodal assessments. To resolve these issues, we introduce LiveProteinBench, a contamination-free, multimodal benchmark of 12 tasks for evaluating LLM performance on protein property and function prediction. Its central innovation lies in a test set composed exclusively of proteins validated after the start of 2025, guaranteeing that the data is novel to all tested models. We benchmarked a suite of prominent general-purpose LLMs and specialized biological LLMs using both unimodal and multimodal input schemes. Our results show that: 1) General-purpose proprietary large models demonstrate superior zero-shot performance when encountering new protein data, outperforming their open-source and domain-specific counterparts by over 20\% accuracy. 2) The effective use of multi-view structural information remains a significant challenge, as the inclusion of structural images often fails to provide a consistent benefit and can even degrade performance. This highlights the limitations of current models in effectively fusing information across different modalities. 3) Models' performance scales more directly with the computational cost during inference than with its parameter count, underscoring the critical role of Chain-of-Thought reasoning capabilities for protein-specific tasks. LiveProteinBench delineates the current performance frontiers for LLMs in bioinformatics and presents new challenges for the development of future multimodal foundation models for biology

In this paper, we propose a new class of metric for table structure recognition (TSR) evaluation, called grid table similarity (GriTS). Unlike prior metrics, GriTS evaluates the correctness of a predicted table directly in its natural form as a matrix. To create a similarity measure between matrices, we generalize the two-dimensional largest common substructure (2D-LCS) problem, which is NP-hard, to the 2D most similar substructures (2D-MSS) problem and propose a polynomial-time heuristic for solving it. This algorithm produces both an upper and a lower bound on the true similarity between matrices. We show using evaluation on a large real-world dataset that in practice there is almost no difference between these bounds. We compare GriTS to other metrics and empirically validate that matrix similarity exhibits more desirable behavior than alternatives for TSR performance evaluation. Finally, GriTS unifies all three subtasks of cell topology recognition, cell location recognition, and cell content recognition within the same framework, which simplifies the evaluation and enables more meaningful comparisons across different types of TSR approaches. Code will be released at https://github.com/microsoft/table-transformer.

Recently, studies exemplified by Hyper-Connections (HC) have extended the ubiquitous residual connection paradigm established over the past decade by expanding the residual stream width and diversifying connectivity patterns. While yielding substantial performance gains, this diversification fundamentally compromises the identity mapping property intrinsic to the residual connection, which causes severe training instability and restricted scalability, and additionally incurs notable memory access overhead. To address these challenges, we propose Manifold-Constrained Hyper-Connections (mHC), a general framework that projects the residual connection space of HC onto a specific manifold to restore the identity mapping property, while incorporating rigorous infrastructure optimization to ensure efficiency. Empirical experiments demonstrate that mHC is effective for training at scale, offering tangible performance improvements and superior scalability. We anticipate that mHC, as a flexible and practical extension of HC, will contribute to a deeper understanding of topological architecture design and suggest promising directions for the evolution of foundational models.

Protein modeling is an increasingly popular area of machine learning research. Semi-supervised learning has emerged as an important paradigm in protein modeling due to the high cost of acquiring supervised protein labels, but the current literature is fragmented when it comes to datasets and standardized evaluation techniques. To facilitate progress in this field, we introduce the Tasks Assessing Protein Embeddings (TAPE), a set of five biologically relevant semi-supervised learning tasks spread across different domains of protein biology. We curate tasks into specific training, validation, and test splits to ensure that each task tests biologically relevant generalization that transfers to real-life scenarios. We benchmark a range of approaches to semi-supervised protein representation learning, which span recent work as well as canonical sequence learning techniques. We find that self-supervised pretraining is helpful for almost all models on all tasks, more than doubling performance in some cases. Despite this increase, in several cases features learned by self-supervised pretraining still lag behind features extracted by state-of-the-art non-neural techniques. This gap in performance suggests a huge opportunity for innovative architecture design and improved modeling paradigms that better capture the signal in biological sequences. TAPE will help the machine learning community focus effort on scientifically relevant problems. Toward this end, all data and code used to run these experiments are available at https://github.com/songlab-cal/tape.

With the surge in available data from various modalities, there is a growing need to bridge the gap between different data types. In this work, we introduce a novel approach to learn cross-modal representations between image data and molecular representations for drug discovery. We propose EMM and IMM, two innovative loss functions built on top of CLIP that leverage weak supervision and cross sites replicates in High-Content Screening. Evaluating our model against known baseline on cross-modal retrieval, we show that our proposed approach allows to learn better representations and mitigate batch effect. In addition, we also present a preprocessing method for the JUMP-CP dataset that effectively reduce the required space from 85Tb to a mere usable 7Tb size, still retaining all perturbations and most of the information content.

In recent decades, chemistry publications and patents have increased rapidly. A significant portion of key information is embedded in molecular structure figures, complicating large-scale literature searches and limiting the application of large language models in fields such as biology, chemistry, and pharmaceuticals. The automatic extraction of precise chemical structures is of critical importance. However, the presence of numerous Markush structures in real-world documents, along with variations in molecular image quality, drawing styles, and noise, significantly limits the performance of existing optical chemical structure recognition (OCSR) methods. We present MolParser, a novel end-to-end OCSR method that efficiently and accurately recognizes chemical structures from real-world documents, including difficult Markush structure. We use a extended SMILES encoding rule to annotate our training dataset. Under this rule, we build MolParser-7M, the largest annotated molecular image dataset to our knowledge. While utilizing a large amount of synthetic data, we employed active learning methods to incorporate substantial in-the-wild data, specifically samples cropped from real patents and scientific literature, into the training process. We trained an end-to-end molecular image captioning model, MolParser, using a curriculum learning approach. MolParser significantly outperforms classical and learning-based methods across most scenarios, with potential for broader downstream applications. The dataset is publicly available.

We present a geometric framework for filtered approximate nearest neighbor (ANN) search. Filtering a proximity graph by a metadata predicate produces a subgraph, a fiber, whose connectivity and geometry can differ sharply from the full graph. Using local signals, we propose a two-phase search algorithm that combines full-graph exploration with filtered-neighbor descent when the local geometry is favorable. These signals also classify search failures into three regimes: topological cuts, geometric folds, and genuine basins. A key observation is that all three share a common resolution: restarting the search in a fiber-present cluster near the query. To support this, we introduce a lightweight anchor structure that identifies such regions and restarts the search accordingly. We show empirically that the method outperforms FAISS HNSW on filtered search and the three failure regimes separate cleanly and shift predictably with filter selectivity.

Understanding biological processes, drug development, and biotechnological advancements requires detailed analysis of protein structures and sequences, a task in protein research that is inherently complex and time-consuming when performed manually. To streamline this process, we introduce ProteinGPT, a state-of-the-art multi-modal protein chat system, that allows users to upload protein sequences and/or structures for comprehensive protein analysis and responsive inquiries. ProteinGPT seamlessly integrates protein sequence and structure encoders with linear projection layers for precise representation adaptation, coupled with a large language model (LLM) to generate accurate and contextually relevant responses. To train ProteinGPT, we construct a large-scale dataset of 132,092 proteins with annotations, and optimize the instruction-tuning process using GPT-4o. This innovative system ensures accurate alignment between the user-uploaded data and prompts, simplifying protein analysis. Experiments show that ProteinGPT can produce promising responses to proteins and their corresponding questions.

Immunohistochemical (IHC) staining highlights the molecular information critical to diagnostics in tissue samples. However, compared to H&E staining, IHC staining can be much more expensive in terms of both labor and the laboratory equipment required. This motivates recent research that demonstrates that the correlations between the morphological information present in the H&E-stained slides and the molecular information in the IHC-stained slides can be used for H&E-to-IHC stain translation. However, due to a lack of pixel-perfect H&E-IHC groundtruth pairs, most existing methods have resorted to relying on expert annotations. To remedy this situation, we present a new loss function, Adaptive Supervised PatchNCE (ASP), to directly deal with the input to target inconsistencies in a proposed H&E-to-IHC image-to-image translation framework. The ASP loss is built upon a patch-based contrastive learning criterion, named Supervised PatchNCE (SP), and augments it further with weight scheduling to mitigate the negative impact of noisy supervision. Lastly, we introduce the Multi-IHC Stain Translation (MIST) dataset, which contains aligned H&E-IHC patches for 4 different IHC stains critical to breast cancer diagnosis. In our experiment, we demonstrate that our proposed method outperforms existing image-to-image translation methods for stain translation to multiple IHC stains. All of our code and datasets are available at https://github.com/lifangda01/AdaptiveSupervisedPatchNCE.

The integration of biomolecular modeling with natural language (BL) has emerged as a promising interdisciplinary area at the intersection of artificial intelligence, chemistry and biology. This approach leverages the rich, multifaceted descriptions of biomolecules contained within textual data sources to enhance our fundamental understanding and enable downstream computational tasks such as biomolecule property prediction. The fusion of the nuanced narratives expressed through natural language with the structural and functional specifics of biomolecules described via various molecular modeling techniques opens new avenues for comprehensively representing and analyzing biomolecules. By incorporating the contextual language data that surrounds biomolecules into their modeling, BL aims to capture a holistic view encompassing both the symbolic qualities conveyed through language as well as quantitative structural characteristics. In this review, we provide an extensive analysis of recent advancements achieved through cross modeling of biomolecules and natural language. (1) We begin by outlining the technical representations of biomolecules employed, including sequences, 2D graphs, and 3D structures. (2) We then examine in depth the rationale and key objectives underlying effective multi-modal integration of language and molecular data sources. (3) We subsequently survey the practical applications enabled to date in this developing research area. (4) We also compile and summarize the available resources and datasets to facilitate future work. (5) Looking ahead, we identify several promising research directions worthy of further exploration and investment to continue advancing the field. The related resources and contents are updating in https://github.com/QizhiPei/Awesome-Biomolecule-Language-Cross-Modeling.

Contrastive Vision-Language Models (VLMs) have demonstrated strong zero-shot capabilities. However, their cross-modal alignment remains biased toward English due to limited multilingual multimodal data. Recent multilingual extensions have alleviated this gap but enforce instance-level alignment while neglecting the global geometry of the shared embedding space. We address this problem by introducing ToMCLIP (Topological Alignment for Multilingual CLIP), a topology-aware framework aligning embedding spaces with topology-preserving constraints. The proposed method applies persistent homology to define a topological alignment loss and approximates persistence diagram with theoretical error bounds using graph sparsification strategy. This work validates the proposed approach, showing enhanced structural coherence of multilingual representations, higher zero-shot accuracy on the CIFAR-100, and stronger multilingual retrieval performance on the xFlickr&CO. Beyond VLMs, the proposed approach provides a general method for incorporating topological alignment into representation learning. Code is available at https://github.com/junwon0/ToMCLIP.git.

New Intent Discovery (NID) aims to recognize known and infer new intent categories with the help of limited labeled and large-scale unlabeled data. The task is addressed as a feature-clustering problem and recent studies augment instance representation. However, existing methods fail to capture cluster-friendly representations, since they show less capability to effectively control and coordinate within-cluster and between-cluster distances. Tailored to the NID problem, we propose a Robust and Adaptive Prototypical learning (RAP) framework for globally distinct decision boundaries for both known and new intent categories. Specifically, a robust prototypical attracting learning (RPAL) method is designed to compel instances to gravitate toward their corresponding prototype, achieving greater within-cluster compactness. To attain larger between-cluster separation, another adaptive prototypical dispersing learning (APDL) method is devised to maximize the between-cluster distance from the prototype-to-prototype perspective. Experimental results evaluated on three challenging benchmarks (CLINC, BANKING, and StackOverflow) of our method with better cluster-friendly representation demonstrate that RAP brings in substantial improvements over the current state-of-the-art methods (even large language model) by a large margin (average +5.5% improvement).

Scientific archives now contain hundreds of petabytes of data across genomics, ecology, climate, and molecular biology that could reveal undiscovered patterns if systematically analyzed at scale. Large-scale, weakly-supervised datasets in language and vision have driven the development of foundation models whose internal representations encode structure (patterns, co-occurrences and statistical regularities) beyond their training objectives. Most existing methods extract structure only for pre-specified targets; they excel at confirmation but do not support open-ended discovery of unknown patterns. We ask whether sparse autoencoders (SAEs) can enable open-ended feature discovery from foundation model representations. We evaluate this question in controlled rediscovery studies, where the learned SAE features are tested for alignment with semantic concepts on a standard segmentation benchmark and compared against strong label-free alternatives on concept-alignment metrics. Applied to ecological imagery, the same procedure surfaces fine-grained anatomical structure without access to segmentation or part labels, providing a scientific case study with ground-truth validation. While our experiments focus on vision with an ecology case study, the method is domain-agnostic and applicable to models in other sciences (e.g., proteins, genomics, weather). Our results indicate that sparse decomposition provides a practical instrument for exploring what scientific foundation models have learned, an important prerequisite for moving from confirmation to genuine discovery.

Aligning molecular sequence representations (e.g., SMILES notations) with textual descriptions is critical for applications spanning drug discovery, materials design, and automated chemical literature analysis. Existing methodologies typically treat molecular captioning (molecule-to-text) and text-based molecular design (text-to-molecule) as separate tasks, relying on supervised fine-tuning or contrastive learning pipelines. These approaches face three key limitations: (i) conventional metrics like BLEU prioritize linguistic fluency over chemical accuracy, (ii) training datasets frequently contain chemically ambiguous narratives with incomplete specifications, and (iii) independent optimization of generation directions leads to bidirectional inconsistency. To address these issues, we propose RTMol, a bidirectional alignment framework that unifies molecular captioning and text-to-SMILES generation through self-supervised round-trip learning. The framework introduces novel round-trip evaluation metrics and enables unsupervised training for molecular captioning without requiring paired molecule-text corpora. Experiments demonstrate that RTMol enhances bidirectional alignment performance by up to 47% across various LLMs, establishing an effective paradigm for joint molecule-text understanding and generation.

Identifying the chemical structure from a graphical representation, or image, of a molecule is a challenging pattern recognition task that would greatly benefit drug development. Yet, existing methods for chemical structure recognition do not typically generalize well, and show diminished effectiveness when confronted with domains where data is sparse, or costly to generate, such as hand-drawn molecule images. To address this limitation, we propose a new chemical structure recognition tool that delivers state-of-the-art performance and can adapt to new domains with a limited number of data samples and supervision. Unlike previous approaches, our method provides atom-level localization, and can therefore segment the image into the different atoms and bonds. Our model is the first model to perform OCSR with atom-level entity detection with only SMILES supervision. Through rigorous and extensive benchmarking, we demonstrate the preeminence of our chemical structure recognition approach in terms of data efficiency, accuracy, and atom-level entity prediction.

Scientific problem-solving involves synthesizing information while applying expert knowledge. We introduce CURIE, a scientific long-Context Understanding,Reasoning and Information Extraction benchmark to measure the potential of Large Language Models (LLMs) in scientific problem-solving and assisting scientists in realistic workflows. This benchmark introduces ten challenging tasks with a total of 580 problems and solution pairs curated by experts in six disciplines - materials science, condensed matter physics, quantum computing, geospatial analysis, biodiversity, and proteins - covering both experimental and theoretical work-flows in science. We evaluate a range of closed and open LLMs on tasks in CURIE which requires domain expertise, comprehension of long in-context information,and multi-step reasoning. While Gemini Flash 2.0 and Claude-3 show consistent high comprehension across domains, the popular GPT-4o and command-R+ fail dramatically on protein sequencing tasks. With the best performance at 32% there is much room for improvement for all models. We hope that insights gained from CURIE can guide the future development of LLMs in sciences. Evaluation code and data are in https://github.com/google/curie

Multi-turn-to-single-turn (M2S) compresses iterative red-teaming into one structured prompt, but prior work relied on a handful of manually written templates. We present X-Teaming Evolutionary M2S, an automated framework that discovers and optimizes M2S templates through language-model-guided evolution. The system pairs smart sampling from 12 sources with an LLM-as-judge inspired by StrongREJECT and records fully auditable logs. Maintaining selection pressure by setting the success threshold to theta = 0.70, we obtain five evolutionary generations, two new template families, and 44.8% overall success (103/230) on GPT-4.1. A balanced cross-model panel of 2,500 trials (judge fixed) shows that structural gains transfer but vary by target; two models score zero at the same threshold. We also find a positive coupling between prompt length and score, motivating length-aware judging. Our results demonstrate that structure-level search is a reproducible route to stronger single-turn probes and underscore the importance of threshold calibration and cross-model evaluation. Code, configurations, and artifacts are available at https://github.com/hyunjun1121/M2S-x-teaming.

Multimodal relation extraction (MRE) is a crucial task in the fields of Knowledge Graph and Multimedia, playing a pivotal role in multimodal knowledge graph construction. However, existing methods are typically limited to extracting a single type of relational triplet, which restricts their ability to extract triplets beyond the specified types. Directly combining these methods fails to capture dynamic cross-modal interactions and introduces significant computational redundancy. Therefore, we propose a novel unified multimodal Relation Extraction framework with Multilevel Optimal Transport and mixture-of-Experts, termed REMOTE, which can simultaneously extract intra-modal and inter-modal relations between textual entities and visual objects. To dynamically select optimal interaction features for different types of relational triplets, we introduce mixture-of-experts mechanism, ensuring the most relevant modality information is utilized. Additionally, considering that the inherent property of multilayer sequential encoding in existing encoders often leads to the loss of low-level information, we adopt a multilevel optimal transport fusion module to preserve low-level features while maintaining multilayer encoding, yielding more expressive representations. Correspondingly, we also create a Unified Multimodal Relation Extraction (UMRE) dataset to evaluate the effectiveness of our framework, encompassing diverse cases where the head and tail entities can originate from either text or image. Extensive experiments show that REMOTE effectively extracts various types of relational triplets and achieves state-of-the-art performanc on almost all metrics across two other public MRE datasets. We release our resources at https://github.com/Nikol-coder/REMOTE.

The detection of ligand binding sites for proteins is a fundamental step in Structure-Based Drug Design. Despite notable advances in recent years, existing methods, datasets, and evaluation metrics are confronted with several key challenges: (1) current datasets and methods are centered on individual protein-ligand complexes and neglect that diverse binding sites may exist across multiple complexes of the same protein, introducing significant statistical bias; (2) ligand binding site detection is typically modeled as a discontinuous workflow, employing binary segmentation and subsequent clustering algorithms; (3) traditional evaluation metrics do not adequately reflect the actual performance of different binding site prediction methods. To address these issues, we first introduce UniSite-DS, the first UniProt (Unique Protein)-centric ligand binding site dataset, which contains 4.81 times more multi-site data and 2.08 times more overall data compared to the previously most widely used datasets. We then propose UniSite, the first end-to-end ligand binding site detection framework supervised by set prediction loss with bijective matching. In addition, we introduce Average Precision based on Intersection over Union (IoU) as a more accurate evaluation metric for ligand binding site prediction. Extensive experiments on UniSite-DS and several representative benchmark datasets demonstrate that IoU-based Average Precision provides a more accurate reflection of prediction quality, and that UniSite outperforms current state-of-the-art methods in ligand binding site detection. The dataset and codes will be made publicly available at https://github.com/quanlin-wu/unisite.

Molecular knowledge resides within three different modalities of information sources: molecular structures, biomedical documents, and knowledge bases. Effective incorporation of molecular knowledge from these modalities holds paramount significance in facilitating biomedical research. However, existing multimodal molecular foundation models exhibit limitations in capturing intricate connections between molecular structures and texts, and more importantly, none of them attempt to leverage a wealth of molecular expertise derived from knowledge graphs. In this study, we introduce MolFM, a multimodal molecular foundation model designed to facilitate joint representation learning from molecular structures, biomedical texts, and knowledge graphs. We propose cross-modal attention between atoms of molecular structures, neighbors of molecule entities and semantically related texts to facilitate cross-modal comprehension. We provide theoretical analysis that our cross-modal pre-training captures local and global molecular knowledge by minimizing the distance in the feature space between different modalities of the same molecule, as well as molecules sharing similar structures or functions. MolFM achieves state-of-the-art performance on various downstream tasks. On cross-modal retrieval, MolFM outperforms existing models with 12.13% and 5.04% absolute gains under the zero-shot and fine-tuning settings, respectively. Furthermore, qualitative analysis showcases MolFM's implicit ability to provide grounding from molecular substructures and knowledge graphs. Code and models are available on https://github.com/BioFM/OpenBioMed.

The genome sequence contains the blueprint for governing cellular processes. While the availability of genomes has vastly increased over the last decades, experimental annotation of the various functional, non-coding and regulatory elements encoded in the DNA sequence remains both expensive and challenging. This has sparked interest in unsupervised language modeling of genomic DNA, a paradigm that has seen great success for protein sequence data. Although various DNA language models have been proposed, evaluation tasks often differ between individual works, and might not fully recapitulate the fundamental challenges of genome annotation, including the length, scale and sparsity of the data. In this study, we introduce BEND, a Benchmark for DNA language models, featuring a collection of realistic and biologically meaningful downstream tasks defined on the human genome. We find that embeddings from current DNA LMs can approach performance of expert methods on some tasks, but only capture limited information about long-range features. BEND is available at https://github.com/frederikkemarin/BEND.

Text-attributed graphs are widely used across domains, offering rich opportunities for zero-shot learning via graph-text alignment. However, existing methods struggle with tasks requiring fine-grained pattern recognition, particularly on heterophilic graphs. Through empirical and theoretical analysis, we identify an over-abstraction problem: current approaches operate at excessively large hyperbolic radii, compressing multi-scale structural information into uniform high-level abstractions. This abstraction-induced information loss obscures critical local patterns essential for accurate predictions. By analyzing embeddings in hyperbolic space, we demonstrate that optimal graph learning requires faithful preservation of fine-grained structural details, better retained by representations positioned closer to the origin. To address this, we propose H4G, a framework that systematically reduces embedding radii using learnable block-diagonal scaling matrices and M\"obius matrix multiplication. This approach restores access to fine-grained patterns while maintaining global receptive ability with minimal computational overhead. Experiments show H4G achieves state-of-the-art zero-shot performance with 12.8\% improvement on heterophilic graphs and 8.4\% on homophilic graphs, confirming that radius reduction enables faithful multi-scale representation for advancing zero-shot graph learning.

Extended-connectivity fingerprints (ECFPs) are a ubiquitous tool in current cheminformatics and molecular machine learning, and one of the most prevalent molecular feature extraction techniques used for chemical prediction. Atom features learned by graph neural networks can be aggregated to compound-level representations using a large spectrum of graph pooling methods; in contrast, sets of detected ECFP substructures are by default transformed into bit vectors using only a simple hash-based folding procedure. We introduce a general mathematical framework for the vectorisation of structural fingerprints via a formal operation called substructure pooling that encompasses hash-based folding, algorithmic substructure-selection, and a wide variety of other potential techniques. We go on to describe Sort & Slice, an easy-to-implement and bit-collision-free alternative to hash-based folding for the pooling of ECFP substructures. Sort & Slice first sorts ECFP substructures according to their relative prevalence in a given set of training compounds and then slices away all but the L most frequent substructures which are subsequently used to generate a binary fingerprint of desired length, L. We computationally compare the performance of hash-based folding, Sort & Slice, and two advanced supervised substructure-selection schemes (filtering and mutual-information maximisation) for ECFP-based molecular property prediction. Our results indicate that, despite its technical simplicity, Sort & Slice robustly (and at times substantially) outperforms traditional hash-based folding as well as the other investigated methods across prediction tasks, data splitting techniques, machine-learning models and ECFP hyperparameters. We thus recommend that Sort & Slice canonically replace hash-based folding as the default substructure-pooling technique to vectorise ECFPs for supervised molecular machine learning.

In recent years, protein-text models have gained significant attention for their potential in protein generation and understanding. Current approaches focus on integrating protein-related knowledge into large language models through continued pretraining and multi-modal alignment, enabling simultaneous comprehension of textual descriptions and protein sequences. Through a thorough analysis of existing model architectures and text-based protein understanding benchmarks, we identify significant data leakage issues present in current benchmarks. Moreover, conventional metrics derived from natural language processing fail to accurately assess the model's performance in this domain. To address these limitations, we reorganize existing datasets and introduce a novel evaluation framework based on biological entities. Motivated by our observation, we propose a retrieval-enhanced method, which significantly outperforms fine-tuned LLMs for protein-to-text generation and shows accuracy and efficiency in training-free scenarios. Our code and data can be seen at https://github.com/IDEA-XL/RAPM.

Large language models (LLMs) have shown significant potential in scientific disciplines such as biomedicine, particularly in hypothesis generation, where they can analyze vast literature, identify patterns, and suggest research directions. However, a key challenge lies in evaluating the truthfulness of generated hypotheses, as verifying their accuracy often requires substantial time and resources. Additionally, the hallucination problem in LLMs can lead to the generation of hypotheses that appear plausible but are ultimately incorrect, undermining their reliability. To facilitate the systematic study of these challenges, we introduce TruthHypo, a benchmark for assessing the capabilities of LLMs in generating truthful biomedical hypotheses, and KnowHD, a knowledge-based hallucination detector to evaluate how well hypotheses are grounded in existing knowledge. Our results show that LLMs struggle to generate truthful hypotheses. By analyzing hallucinations in reasoning steps, we demonstrate that the groundedness scores provided by KnowHD serve as an effective metric for filtering truthful hypotheses from the diverse outputs of LLMs. Human evaluations further validate the utility of KnowHD in identifying truthful hypotheses and accelerating scientific discovery. Our data and source code are available at https://github.com/Teddy-XiongGZ/TruthHypo.

Image-text retrieval has developed rapidly in recent years. However, it is still a challenge in remote sensing due to visual-semantic imbalance, which leads to incorrect matching of non-semantic visual and textual features. To solve this problem, we propose a novel Direction-Oriented Visual-semantic Embedding Model (DOVE) to mine the relationship between vision and language. Our highlight is to conduct visual and textual representations in latent space, directing them as close as possible to a redundancy-free regional visual representation. Concretely, a Regional-Oriented Attention Module (ROAM) adaptively adjusts the distance between the final visual and textual embeddings in the latent semantic space, oriented by regional visual features. Meanwhile, a lightweight Digging Text Genome Assistant (DTGA) is designed to expand the range of tractable textual representation and enhance global word-level semantic connections using less attention operations. Ultimately, we exploit a global visual-semantic constraint to reduce single visual dependency and serve as an external constraint for the final visual and textual representations. The effectiveness and superiority of our method are verified by extensive experiments including parameter evaluation, quantitative comparison, ablation studies and visual analysis, on two benchmark datasets, RSICD and RSITMD.

Local graph clustering methods aim to detect small clusters in very large graphs without the need to process the whole graph. They are fundamental and scalable tools for a wide range of tasks such as local community detection, node ranking and node embedding. While prior work on local graph clustering mainly focuses on graphs without node attributes, modern real-world graph datasets typically come with node attributes that provide valuable additional information. We present a simple local graph clustering algorithm for graphs with node attributes, based on the idea of diffusing mass locally in the graph while accounting for both structural and attribute proximities. Using high-dimensional concentration results, we provide statistical guarantees on the performance of the algorithm for the recovery of a target cluster with a single seed node. We give conditions under which a target cluster generated from a fairly general contextual random graph model, which includes both the stochastic block model and the planted cluster model as special cases, can be fully recovered with bounded false positives. Empirically, we validate all theoretical claims using synthetic data, and we show that incorporating node attributes leads to superior local clustering performances using real-world graph datasets.

We are now witnessing significant progress of deep learning methods in a variety of tasks (or datasets) of proteins. However, there is a lack of a standard benchmark to evaluate the performance of different methods, which hinders the progress of deep learning in this field. In this paper, we propose such a benchmark called PEER, a comprehensive and multi-task benchmark for Protein sEquence undERstanding. PEER provides a set of diverse protein understanding tasks including protein function prediction, protein localization prediction, protein structure prediction, protein-protein interaction prediction, and protein-ligand interaction prediction. We evaluate different types of sequence-based methods for each task including traditional feature engineering approaches, different sequence encoding methods as well as large-scale pre-trained protein language models. In addition, we also investigate the performance of these methods under the multi-task learning setting. Experimental results show that large-scale pre-trained protein language models achieve the best performance for most individual tasks, and jointly training multiple tasks further boosts the performance. The datasets and source codes of this benchmark are all available at https://github.com/DeepGraphLearning/PEER_Benchmark

Recent advances have discussed cell complexes as ideal learning representations. However, there is a lack of available machine learning methods suitable for learning on CW complexes. In this paper, we derive an explicit expression for the Wasserstein distance between cell complex signal distributions in terms of a Hodge-Laplacian matrix. This leads to a structurally meaningful measure to compare CW complexes and define the optimal transportation map. In order to simultaneously include both feature and structure information, we extend the Fused Gromov-Wasserstein distance to CW complexes. Finally, we introduce novel kernels over the space of probability measures on CW complexes based on the dual formulation of optimal transport.

Scientific Large Language Models (Sci-LLMs) have emerged as a promising frontier for accelerating biological discovery. However, these models face a fundamental challenge when processing raw biomolecular sequences: the tokenization dilemma. Whether treating sequences as a specialized language, risking the loss of functional motif information, or as a separate modality, introducing formidable alignment challenges, current strategies fundamentally limit their reasoning capacity. We challenge this sequence-centric paradigm by positing that a more effective strategy is to provide Sci-LLMs with high-level structured context derived from established bioinformatics tools, thereby bypassing the need to interpret low-level noisy sequence data directly. Through a systematic comparison of leading Sci-LLMs on biological reasoning tasks, we tested three input modes: sequence-only, context-only, and a combination of both. Our findings are striking: the context-only approach consistently and substantially outperforms all other modes. Even more revealing, the inclusion of the raw sequence alongside its high-level context consistently degrades performance, indicating that raw sequences act as informational noise, even for models with specialized tokenization schemes. These results suggest that the primary strength of existing Sci-LLMs lies not in their nascent ability to interpret biomolecular syntax from scratch, but in their profound capacity for reasoning over structured, human-readable knowledge. Therefore, we argue for reframing Sci-LLMs not as sequence decoders, but as powerful reasoning engines over expert knowledge. This work lays the foundation for a new class of hybrid scientific AI agents, repositioning the developmental focus from direct sequence interpretation towards high-level knowledge synthesis. The code is available at https://github.com/opendatalab-raiser/CoKE.

In this work, we show that it is possible to extract significant amounts of alignment training data from a post-trained model -- useful to steer the model to improve certain capabilities such as long-context reasoning, safety, instruction following, and maths. While the majority of related work on memorisation has focused on measuring success of training data extraction through string matching, we argue that embedding models are better suited for our specific goals. Distances measured through a high quality embedding model can identify semantic similarities between strings that a different metric such as edit distance will struggle to capture. In fact, in our investigation, approximate string matching would have severely undercounted (by a conservative estimate of 10times) the amount of data that can be extracted due to trivial artifacts that deflate the metric. Interestingly, we find that models readily regurgitate training data that was used in post-training phases such as SFT or RL. We show that this data can be then used to train a base model, recovering a meaningful amount of the original performance. We believe our work exposes a possibly overlooked risk towards extracting alignment data. Finally, our work opens up an interesting discussion on the downstream effects of distillation practices: since models seem to be regurgitating aspects of their training set, distillation can therefore be thought of as indirectly training on the model's original dataset.

Multimodal retrieval is becoming a crucial component of modern AI applications, yet its evaluation lags behind the demands of more realistic and challenging scenarios. Existing benchmarks primarily probe surface-level semantic correspondence (e.g., object-text matching) while failing to assess the deeper reasoning required to capture complex relationships between visual and textual information. To address this gap, we introduce MR^2-Bench, a reasoning-intensive benchmark for multimodal retrieval. MR^2-Bench presents the following critical values: 1) all tasks are reasoning-driven, going beyond shallow matching to effectively assess models' capacity for logical, spatial, and causal inference; 2) it features diverse multimodal data, such as natural images, diagrams, and visual puzzles, enabling comprehensive evaluation across content types; 3) it supports complex queries and documents containing multiple images and covers diverse retrieval scenarios, more accurately reflecting real-world applications. Our benchmark contains 1,309 curated queries, derived either from manual collection and annotation or from selective consolidation of public datasets. Despite achieving strong results on existing benchmarks, current state-of-the-art models still struggle on MR^2-Bench: for example, the leading Seed1.6-Embedding model attains a Recall@1 of 77.78 on MMEB, but only 9.91 on MR^2-Bench. This substantial performance gap highlights both the increased challenge posed by our benchmark and the pressing need for further advances in reasoning-intensive multimodal retrieval. The dataset and evaluation code will be made publicly available at https://github.com/VectorSpaceLab/MR2-Bench.

Object appearances change dramatically with pose variations. This creates a challenge for embedding schemes that seek to map instances with the same object ID to locations that are as close as possible. This issue becomes significantly heightened in complex computer vision tasks such as re-identification(reID). In this paper, we suggest that these dramatic appearance changes are indications that an object ID is composed of multiple natural groups, and it is counterproductive to forcefully map instances from different groups to a common location. This leads us to introduce Relation Preserving Triplet Mining (RPTM), a feature-matching guided triplet mining scheme, that ensures that triplets will respect the natural subgroupings within an object ID. We use this triplet mining mechanism to establish a pose-aware, well-conditioned triplet loss by implicitly enforcing view consistency. This allows a single network to be trained with fixed parameters across datasets while providing state-of-the-art results. Code is available at https://github.com/adhirajghosh/RPTM_reid.

We build upon vec2vec, a procedure designed to align text embedding spaces without parallel data. vec2vec finds a near-perfect alignment, but it is expensive and unstable. We present mini-vec2vec, a simple and efficient alternative that requires substantially lower computational cost and is highly robust. Moreover, the learned mapping is a linear transformation. Our method consists of three main stages: a tentative matching of pseudo-parallel embedding vectors, transformation fitting, and iterative refinement. Our linear alternative exceeds the original instantiation of vec2vec by orders of magnitude in efficiency, while matching or exceeding their results. The method's stability and interpretable algorithmic steps facilitate scaling and unlock new opportunities for adoption in new domains and fields.

This paper introduces the concept of Microscopic Spatial Intelligence (MiSI), the capability to perceive and reason about the spatial relationships of invisible microscopic entities, which is fundamental to scientific discovery. To assess the potential of Vision-Language Models (VLMs) in this domain, we propose a systematic benchmark framework MiSI-Bench. This framework features over 163,000 question-answer pairs and 587,000 images derived from approximately 4,000 molecular structures, covering nine complementary tasks that evaluate abilities ranging from elementary spatial transformations to complex relational identifications. Experimental results reveal that current state-of-the-art VLMs perform significantly below human level on this benchmark. However, a fine-tuned 7B model demonstrates substantial potential, even surpassing humans in spatial transformation tasks, while its poor performance in scientifically-grounded tasks like hydrogen bond recognition underscores the necessity of integrating explicit domain knowledge for progress toward scientific AGI. The datasets are available at https://huggingface.co/datasets/zongzhao/MiSI-bench.

We introduce the first method for translating text embeddings from one vector space to another without any paired data, encoders, or predefined sets of matches. Our unsupervised approach translates any embedding to and from a universal latent representation (i.e., a universal semantic structure conjectured by the Platonic Representation Hypothesis). Our translations achieve high cosine similarity across model pairs with different architectures, parameter counts, and training datasets. The ability to translate unknown embeddings into a different space while preserving their geometry has serious implications for the security of vector databases. An adversary with access only to embedding vectors can extract sensitive information about the underlying documents, sufficient for classification and attribute inference.

Motivation: The activity of the adaptive immune system is governed by T-cells and their specific T-cell receptors (TCR), which selectively recognize foreign antigens. Recent advances in experimental techniques have enabled sequencing of TCRs and their antigenic targets (epitopes), allowing to research the missing link between TCR sequence and epitope binding specificity. Scarcity of data and a large sequence space make this task challenging, and to date only models limited to a small set of epitopes have achieved good performance. Here, we establish a k-nearest-neighbor (K-NN) classifier as a strong baseline and then propose TITAN (Tcr epITope bimodal Attention Networks), a bimodal neural network that explicitly encodes both TCR sequences and epitopes to enable the independent study of generalization capabilities to unseen TCRs and/or epitopes. Results: By encoding epitopes at the atomic level with SMILES sequences, we leverage transfer learning and data augmentation to enrich the input data space and boost performance. TITAN achieves high performance in the prediction of specificity of unseen TCRs (ROC-AUC 0.87 in 10-fold CV) and surpasses the results of the current state-of-the-art (ImRex) by a large margin. Notably, our Levenshtein-distance-based K-NN classifier also exhibits competitive performance on unseen TCRs. While the generalization to unseen epitopes remains challenging, we report two major breakthroughs. First, by dissecting the attention heatmaps, we demonstrate that the sparsity of available epitope data favors an implicit treatment of epitopes as classes. This may be a general problem that limits unseen epitope performance for sufficiently complex models. Second, we show that TITAN nevertheless exhibits significantly improved performance on unseen epitopes and is capable of focusing attention on chemically meaningful molecular structures.

Molecular function is largely determined by structure. Accurately aligning molecular structure with natural language is therefore essential for enabling large language models (LLMs) to reason about downstream chemical tasks. However, the substantial cost of human annotation makes it infeasible to construct large-scale, high-quality datasets of structure-grounded descriptions. In this work, we propose a fully automated annotation framework for generating precise molecular structure descriptions at scale. Our approach builds upon and extends a rule-based chemical nomenclature parser to interpret IUPAC names and construct enriched, structured XML metadata that explicitly encodes molecular structure. This metadata is then used to guide LLMs in producing accurate natural-language descriptions. Using this framework, we curate a large-scale dataset of approximately 163k molecule-description pairs. A rigorous validation protocol combining LLM-based and expert human evaluation on a subset of 2,000 molecules demonstrates a high description precision of 98.6%. The resulting dataset provides a reliable foundation for future molecule-language alignment, and the proposed annotation method is readily extensible to larger datasets and broader chemical tasks that rely on structural descriptions.

Recent studies in DNA sequence classification have leveraged sophisticated machine learning techniques, achieving notable accuracy in categorizing complex genomic data. Among these, methods such as k-mer counting have proven effective in distinguishing sequences from varied species like chimpanzees, dogs, and humans, becoming a staple in contemporary genomic research. However, these approaches often demand extensive computational resources, posing a challenge in terms of scalability and efficiency. Addressing this issue, our study introduces a novel adaptation of Jiang et al.'s compressor-based, parameter-free classification method, specifically tailored for DNA sequence analysis. This innovative approach utilizes a variety of compression algorithms, such as Gzip, Brotli, and LZMA, to efficiently process and classify genomic sequences. Not only does this method align with the current state-of-the-art in terms of accuracy, but it also offers a more resource-efficient alternative to traditional machine learning methods. Our comprehensive evaluation demonstrates the proposed method's effectiveness in accurately classifying DNA sequences from multiple species. We present a detailed analysis of the performance of each algorithm used, highlighting the strengths and limitations of our approach in various genomic contexts. Furthermore, we discuss the broader implications of our findings for bioinformatics, particularly in genomic data processing and analysis. The results of our study pave the way for more efficient and scalable DNA sequence classification methods, offering significant potential for advancements in genomic research and applications.

Leaf-lesion segmentation is topology-sensitive: small merges, splits, or false holes can be biologically meaningful descriptors of biochemical pathways, yet they are weakly penalized by standard pixel-wise losses in Euclidean latents. I explore HyperTopo-Adapters, a lightweight, parameter-efficient head trained on top of a frozen vision encoder, which embeds features on a product manifold -- hyperbolic + Euclidean + spherical (H + E + S) -- to encourage hierarchical separation (H), local linear detail (E), and global closure (S). A topology prior complements Dice/BCE in two forms: (i) persistent-homology (PH) distance for evaluation and selection, and (ii) a differentiable surrogate that combines a soft Euler-characteristic match with total variation regularization for stable training. I introduce warm-ups for both the hyperbolic contrastive term and the topology prior, per-sample evaluation of structure-aware metrics (Boundary-F1, Betti errors, PD distance), and a min-PD within top-K Dice rule for checkpoint selection. On a Kaggle leaf-lesion dataset (N=2,940), early results show consistent gains in boundary and topology metrics (reducing Delta beta_1 hole error by 9%) while Dice/IoU remain competitive. The study is diagnostic by design: I report controlled ablations (curvature learning, latent dimensions, contrastive temperature, surrogate settings), and ongoing tests varying encoder strength (ResNet-50, DeepLabV3, DINOv2/v3), input resolution, PH weight, and partial unfreezing of late blocks. The contribution is an open, reproducible train/eval suite (available at https://github.com/ChimdiWalter/HyperTopo-Adapters) that isolates geometric/topological priors and surfaces failure modes to guide stronger, topology-preserving architectures.

Metric space magnitude, an active field of research in algebraic topology, is a scalar quantity that summarizes the effective number of distinct points that live in a general metric space. The {\em weighting vector} is a closely-related concept that captures, in a nontrivial way, much of the underlying geometry of the original metric space. Recent work has demonstrated that when the metric space is Euclidean, the weighting vector serves as an effective tool for boundary detection. We recast this result and show the weighting vector may be viewed as a solution to a kernelized SVM. As one consequence, we apply this new insight to the task of outlier detection, and we demonstrate performance that is competitive or exceeds performance of state-of-the-art techniques on benchmark data sets. Under mild assumptions, we show the weighting vector, which has computational cost of matrix inversion, can be efficiently approximated in linear time. We show how nearest neighbor methods can approximate solutions to the minimization problems defined by SVMs.

Relation extraction in the biomedical domain is challenging due to the lack of labeled data and high annotation costs, needing domain experts. Distant supervision is commonly used to tackle the scarcity of annotated data by automatically pairing knowledge graph relationships with raw texts. Such a pipeline is prone to noise and has added challenges to scale for covering a large number of biomedical concepts. We investigated existing broad-coverage distantly supervised biomedical relation extraction benchmarks and found a significant overlap between training and test relationships ranging from 26% to 86%. Furthermore, we noticed several inconsistencies in the data construction process of these benchmarks, and where there is no train-test leakage, the focus is on interactions between narrower entity types. This work presents a more accurate benchmark MedDistant19 for broad-coverage distantly supervised biomedical relation extraction that addresses these shortcomings and is obtained by aligning the MEDLINE abstracts with the widely used SNOMED Clinical Terms knowledge base. Lacking thorough evaluation with domain-specific language models, we also conduct experiments validating general domain relation extraction findings to biomedical relation extraction.

A common approach for sequence tagging tasks based on contextual word representations is to train a machine learning classifier directly on these embedding vectors. This approach has two shortcomings. First, such methods consider single input sequences in isolation and are unable to put an individual embedding vector in relation to vectors outside the current local context of use. Second, the high performance of these models relies on fine-tuning the embedding model in conjunction with the classifier, which may not always be feasible due to the size or inaccessibility of the underlying feature-generation model. It is thus desirable, given a collection of embedding vectors of a corpus, i.e., a datastore, to find features of each vector that describe its relation to other, similar vectors in the datastore. With this in mind, we introduce complexity measures of the local topology of the latent space of a contextual language model with respect to a given datastore. The effectiveness of our features is demonstrated through their application to dialogue term extraction. Our work continues a line of research that explores the manifold hypothesis for word embeddings, demonstrating that local structure in the space carved out by word embeddings can be exploited to infer semantic properties.

Scientific inquiry requires systems-level reasoning that integrates heterogeneous experimental data, cross-domain knowledge, and mechanistic evidence into coherent explanations. While Large Language Models (LLMs) offer inferential capabilities, they often depend on retrieval-augmented contexts that lack structural depth. Traditional Knowledge Graphs (KGs) attempt to bridge this gap, yet their pairwise constraints fail to capture the irreducible higher-order interactions that govern emergent physical behavior. To address this, we introduce a methodology for constructing hypergraph-based knowledge representations that faithfully encode multi-entity relationships. Applied to a corpus of ~1,100 manuscripts on biocomposite scaffolds, our framework constructs a global hypergraph of 161,172 nodes and 320,201 hyperedges, revealing a scale-free topology (power law exponent ~1.23) organized around highly connected conceptual hubs. This representation prevents the combinatorial explosion typical of pairwise expansions and explicitly preserves the co-occurrence context of scientific formulations. We further demonstrate that equipping agentic systems with hypergraph traversal tools, specifically using node-intersection constraints, enables them to bridge semantically distant concepts. By exploiting these higher-order pathways, the system successfully generates grounded mechanistic hypotheses for novel composite materials, such as linking cerium oxide to PCL scaffolds via chitosan intermediates. This work establishes a "teacherless" agentic reasoning system where hypergraph topology acts as a verifiable guardrail, accelerating scientific discovery by uncovering relationships obscured by traditional graph methods.

Spatial transcriptomics (ST) provides spatially resolved measurements of gene expression, enabling characterization of the molecular landscape of human tissue beyond histological assessment as well as localized readouts that can be aligned with morphology. Concurrently, the success of multimodal foundation models that integrate vision with complementary modalities suggests that morphomolecular coupling between local expression and morphology can be systematically used to improve histological representations themselves. We introduce Spatial Expression-Aligned Learning (SEAL), a vision-omics self-supervised learning framework that infuses localized molecular information into pathology vision encoders. Rather than training new encoders from scratch, SEAL is designed as a parameter-efficient vision-omics finetuning method that can be flexibly applied to widely used pathology foundation models. We instantiate SEAL by training on over 700,000 paired gene expression spot-tissue region examples spanning tumor and normal samples from 14 organs. Tested across 38 slide-level and 15 patch-level downstream tasks, SEAL provides a drop-in replacement for pathology foundation models that consistently improves performance over widely used vision-only and ST prediction baselines on slide-level molecular status, pathway activity, and treatment response prediction, as well as patch-level gene expression prediction tasks. Additionally, SEAL encoders exhibit robust domain generalization on out-of-distribution evaluations and enable new cross-modal capabilities such as gene-to-image retrieval. Our work proposes a general framework for ST-guided finetuning of pathology foundation models, showing that augmenting existing models with localized molecular supervision is an effective and practical step for improving visual representations and expanding their cross-modal utility.

Multiple sequence alignments (MSAs) of proteins encode rich biological information and have been workhorses in bioinformatic methods for tasks like protein design and protein structure prediction for decades. Recent breakthroughs like AlphaFold2 that use transformers to attend directly over large quantities of raw MSAs have reaffirmed their importance. Generation of MSAs is highly computationally intensive, however, and no datasets comparable to those used to train AlphaFold2 have been made available to the research community, hindering progress in machine learning for proteins. To remedy this problem, we introduce OpenProteinSet, an open-source corpus of more than 16 million MSAs, associated structural homologs from the Protein Data Bank, and AlphaFold2 protein structure predictions. We have previously demonstrated the utility of OpenProteinSet by successfully retraining AlphaFold2 on it. We expect OpenProteinSet to be broadly useful as training and validation data for 1) diverse tasks focused on protein structure, function, and design and 2) large-scale multimodal machine learning research.

The digitization of histology slides has revolutionized pathology, providing massive datasets for cancer diagnosis and research. Contrastive self-supervised and vision-language models have been shown to effectively mine large pathology datasets to learn discriminative representations. On the other hand, generative models, capable of synthesizing realistic and diverse images, present a compelling solution to address unique problems in pathology that involve synthesizing images; overcoming annotated data scarcity, enabling privacy-preserving data sharing, and performing inherently generative tasks, such as virtual staining. We introduce PixCell, the first diffusion-based generative foundation model for histopathology. We train PixCell on PanCan-30M, a vast, diverse dataset derived from 69,184 H\&E-stained whole slide images covering various cancer types. We employ a progressive training strategy and a self-supervision-based conditioning that allows us to scale up training without any annotated data. PixCell generates diverse and high-quality images across multiple cancer types, which we find can be used in place of real data to train a self-supervised discriminative model. Synthetic images shared between institutions are subject to fewer regulatory barriers than would be the case with real clinical images. Furthermore, we showcase the ability to precisely control image generation using a small set of annotated images, which can be used for both data augmentation and educational purposes. Testing on a cell segmentation task, a mask-guided PixCell enables targeted data augmentation, improving downstream performance. Finally, we demonstrate PixCell's ability to use H\&E structural staining to infer results from molecular marker studies; we use this capability to infer IHC staining from H\&E images. Our trained models are publicly released to accelerate research in computational pathology.

Inspired by the success of unsupervised pre-training paradigms, researchers have applied these approaches to DNA pre-training. However, we argue that these approaches alone yield suboptimal results because pure DNA sequences lack sufficient information, since their functions are regulated by genomic profiles like chromatin accessibility. Here, we demonstrate that supervised training for genomic profile prediction serves as a more effective alternative to pure sequence pre-training. Furthermore, considering the multi-species and multi-profile nature of genomic profile prediction, we introduce our Species-Profile Adaptive Collaborative Experts (SPACE) that leverages Mixture of Experts (MoE) to better capture the relationships between DNA sequences across different species and genomic profiles, thereby learning more effective DNA representations. Through extensive experiments across various tasks, our model achieves state-of-the-art performance, establishing that DNA models trained with supervised genomic profiles serve as powerful DNA representation learners. The code is available at https://github.com/ZhuJiwei111/SPACE.

We study the problem of visualizing large-scale and high-dimensional data in a low-dimensional (typically 2D or 3D) space. Much success has been reported recently by techniques that first compute a similarity structure of the data points and then project them into a low-dimensional space with the structure preserved. These two steps suffer from considerable computational costs, preventing the state-of-the-art methods such as the t-SNE from scaling to large-scale and high-dimensional data (e.g., millions of data points and hundreds of dimensions). We propose the LargeVis, a technique that first constructs an accurately approximated K-nearest neighbor graph from the data and then layouts the graph in the low-dimensional space. Comparing to t-SNE, LargeVis significantly reduces the computational cost of the graph construction step and employs a principled probabilistic model for the visualization step, the objective of which can be effectively optimized through asynchronous stochastic gradient descent with a linear time complexity. The whole procedure thus easily scales to millions of high-dimensional data points. Experimental results on real-world data sets demonstrate that the LargeVis outperforms the state-of-the-art methods in both efficiency and effectiveness. The hyper-parameters of LargeVis are also much more stable over different data sets.

The extraction of molecular structures and reaction data from scientific documents is challenging due to their varied, unstructured chemical formats and complex document layouts. To address this, we introduce MolMole, a vision-based deep learning framework that unifies molecule detection, reaction diagram parsing, and optical chemical structure recognition (OCSR) into a single pipeline for automating the extraction of chemical data directly from page-level documents. Recognizing the lack of a standard page-level benchmark and evaluation metric, we also present a testset of 550 pages annotated with molecule bounding boxes, reaction labels, and MOLfiles, along with a novel evaluation metric. Experimental results demonstrate that MolMole outperforms existing toolkits on both our benchmark and public datasets. The benchmark testset will be publicly available, and the MolMole toolkit will be accessible soon through an interactive demo on the LG AI Research website. For commercial inquiries, please contact us at mailto:contact_ddu@lgresearch.ai{contact\_ddu@lgresearch.ai}.

Traditional molecular string representations, such as SMILES, often pose challenges for AI-driven molecular design due to their non-sequential depiction of molecular substructures. To address this issue, we introduce Sequential Attachment-based Fragment Embedding (SAFE), a novel line notation for chemical structures. SAFE reimagines SMILES strings as an unordered sequence of interconnected fragment blocks while maintaining full compatibility with existing SMILES parsers. It streamlines complex generative tasks, including scaffold decoration, fragment linking, polymer generation, and scaffold hopping, while facilitating autoregressive generation for fragment-constrained design, thereby eliminating the need for intricate decoding or graph-based models. We demonstrate the effectiveness of SAFE by training an 87-million-parameter GPT2-like model on a dataset containing 1.1 billion SAFE representations. Through extensive experimentation, we show that our SAFE-GPT model exhibits versatile and robust optimization performance. SAFE opens up new avenues for the rapid exploration of chemical space under various constraints, promising breakthroughs in AI-driven molecular design.

Biomedical image analysis is fundamental for biomedical discovery in cell biology, pathology, radiology, and many other biomedical domains. Holistic image analysis comprises interdependent subtasks such as segmentation, detection, and recognition of relevant objects. Here, we propose BiomedParse, a biomedical foundation model for imaging parsing that can jointly conduct segmentation, detection, and recognition for 82 object types across 9 imaging modalities. Through joint learning, we can improve accuracy for individual tasks and enable novel applications such as segmenting all relevant objects in an image through a text prompt, rather than requiring users to laboriously specify the bounding box for each object. We leveraged readily available natural-language labels or descriptions accompanying those datasets and use GPT-4 to harmonize the noisy, unstructured text information with established biomedical object ontologies. We created a large dataset comprising over six million triples of image, segmentation mask, and textual description. On image segmentation, we showed that BiomedParse is broadly applicable, outperforming state-of-the-art methods on 102,855 test image-mask-label triples across 9 imaging modalities (everything). On object detection, which aims to locate a specific object of interest, BiomedParse again attained state-of-the-art performance, especially on objects with irregular shapes (everywhere). On object recognition, which aims to identify all objects in a given image along with their semantic types, we showed that BiomedParse can simultaneously segment and label all biomedical objects in an image (all at once). In summary, BiomedParse is an all-in-one tool for biomedical image analysis by jointly solving segmentation, detection, and recognition for all major biomedical image modalities, paving the path for efficient and accurate image-based biomedical discovery.

We show the existence of a Locality-Sensitive Hashing (LSH) family for the angular distance that yields an approximate Near Neighbor Search algorithm with the asymptotically optimal running time exponent. Unlike earlier algorithms with this property (e.g., Spherical LSH [Andoni, Indyk, Nguyen, Razenshteyn 2014], [Andoni, Razenshteyn 2015]), our algorithm is also practical, improving upon the well-studied hyperplane LSH [Charikar, 2002] in practice. We also introduce a multiprobe version of this algorithm, and conduct experimental evaluation on real and synthetic data sets. We complement the above positive results with a fine-grained lower bound for the quality of any LSH family for angular distance. Our lower bound implies that the above LSH family exhibits a trade-off between evaluation time and quality that is close to optimal for a natural class of LSH functions.

Subcellular localization is a crucial biological task for drug target identification and function annotation. Although it has been biologically realized that subcellular localization is closely associated with protein structure, no existing dataset offers comprehensive 3D structural information with detailed subcellular localization annotations, thus severely hindering the application of promising structure-based models on this task. To address this gap, we introduce a new benchmark called CAPSUL, a Comprehensive humAn Protein benchmark for SUbcellular Localization. It features a dataset that integrates diverse 3D structural representations with fine-grained subcellular localization annotations carefully curated by domain experts. We evaluate this benchmark using a variety of state-of-the-art sequence-based and structure-based models, showcasing the importance of involving structural features in this task. Furthermore, we explore reweighting and single-label classification strategies to facilitate future investigation on structure-based methods for this task. Lastly, we showcase the powerful interpretability of structure-based methods through a case study on the Golgi apparatus, where we discover a decisive localization pattern α-helix from attention mechanisms, demonstrating the potential for bridging the gap with intuitive biological interpretability and paving the way for data-driven discoveries in cell biology.

Hyperbolic embeddings offer excellent quality with few dimensions when embedding hierarchical data structures like synonym or type hierarchies. Given a tree, we give a combinatorial construction that embeds the tree in hyperbolic space with arbitrarily low distortion without using optimization. On WordNet, our combinatorial embedding obtains a mean-average-precision of 0.989 with only two dimensions, while Nickel et al.'s recent construction obtains 0.87 using 200 dimensions. We provide upper and lower bounds that allow us to characterize the precision-dimensionality tradeoff inherent in any hyperbolic embedding. To embed general metric spaces, we propose a hyperbolic generalization of multidimensional scaling (h-MDS). We show how to perform exact recovery of hyperbolic points from distances, provide a perturbation analysis, and give a recovery result that allows us to reduce dimensionality. The h-MDS approach offers consistently low distortion even with few dimensions across several datasets. Finally, we extract lessons from the algorithms and theory above to design a PyTorch-based implementation that can handle incomplete information and is scalable.

To synthesize high-fidelity samples, diffusion models typically require auxiliary data to guide the generation process. However, it is impractical to procure the painstaking patch-level annotation effort required in specialized domains like histopathology and satellite imagery; it is often performed by domain experts and involves hundreds of millions of patches. Modern-day self-supervised learning (SSL) representations encode rich semantic and visual information. In this paper, we posit that such representations are expressive enough to act as proxies to fine-grained human labels. We introduce a novel approach that trains diffusion models conditioned on embeddings from SSL. Our diffusion models successfully project these features back to high-quality histopathology and remote sensing images. In addition, we construct larger images by assembling spatially consistent patches inferred from SSL embeddings, preserving long-range dependencies. Augmenting real data by generating variations of real images improves downstream classifier accuracy for patch-level and larger, image-scale classification tasks. Our models are effective even on datasets not encountered during training, demonstrating their robustness and generalizability. Generating images from learned embeddings is agnostic to the source of the embeddings. The SSL embeddings used to generate a large image can either be extracted from a reference image, or sampled from an auxiliary model conditioned on any related modality (e.g. class labels, text, genomic data). As proof of concept, we introduce the text-to-large image synthesis paradigm where we successfully synthesize large pathology and satellite images out of text descriptions.

Automatic extraction of chemical structures from scientific literature plays a crucial role in accelerating research across fields ranging from drug discovery to materials science. Patent documents, in particular, contain molecular information in visual form, which is often inaccessible through traditional text-based searches. In this work, we introduce SubGrapher, a method for the visual fingerprinting of chemical structure images. Unlike conventional Optical Chemical Structure Recognition (OCSR) models that attempt to reconstruct full molecular graphs, SubGrapher focuses on extracting molecular fingerprints directly from chemical structure images. Using learning-based instance segmentation, SubGrapher identifies functional groups and carbon backbones, constructing a substructure-based fingerprint that enables chemical structure retrieval. Our approach is evaluated against state-of-the-art OCSR and fingerprinting methods, demonstrating superior retrieval performance and robustness across diverse molecular depictions. The dataset, models, and code are publicly available.

Protein structure tokenization converts 3D structures into discrete or vectorized representations, enabling the integration of structural and sequence data. Despite many recent works on structure tokenization, the properties of the underlying discrete representations are not well understood. In this work, we first demonstrate that the successful utilization of structural tokens in a language model for structure prediction depends on using rich, pre-trained sequence embeddings to bridge the semantic gap between the sequence and structural "language". The analysis of the structural vocabulary itself then reveals significant semantic redundancy, where multiple distinct tokens correspond to nearly identical local geometries, acting as "structural synonyms". This redundancy, rather than being a flaw, can be exploited with a simple "synonym swap" strategy to generate diverse conformational ensembles by perturbing a predicted structure with its structural synonyms. This computationally lightweight method accurately recapitulates protein flexibility, performing competitively with state-of-the-art models. Our study provides fundamental insights into the nature of discrete protein structure representations and introduces a powerful, near-instantaneous method for modeling protein dynamics. Source code is available in https://github.com/IDEA-XL/TokenMD.

Efficient computation or approximation of Levenshtein distance, a widely-used metric for evaluating sequence similarity, has attracted significant attention with the emergence of DNA storage and other biological applications. Sequence embedding, which maps Levenshtein distance to a conventional distance between embedding vectors, has emerged as a promising solution. In this paper, a novel neural network-based sequence embedding technique using Poisson regression is proposed. We first provide a theoretical analysis of the impact of embedding dimension on model performance and present a criterion for selecting an appropriate embedding dimension. Under this embedding dimension, the Poisson regression is introduced by assuming the Levenshtein distance between sequences of fixed length following a Poisson distribution, which naturally aligns with the definition of Levenshtein distance. Moreover, from the perspective of the distribution of embedding distances, Poisson regression approximates the negative log likelihood of the chi-squared distribution and offers advancements in removing the skewness. Through comprehensive experiments on real DNA storage data, we demonstrate the superior performance of the proposed method compared to state-of-the-art approaches.

Cross-modal metric learning is a prominent research topic that bridges the semantic heterogeneity between vision and language. Existing methods frequently utilize simple cosine or complex distance metrics to transform the pairwise features into a similarity score, which suffers from an inadequate or inefficient capability for distance measurements. Consequently, we propose a Generalized Structural Sparse Function to dynamically capture thorough and powerful relationships across modalities for pair-wise similarity learning while remaining concise but efficient. Specifically, the distance metric delicately encapsulates two formats of diagonal and block-diagonal terms, automatically distinguishing and highlighting the cross-channel relevancy and dependency inside a structured and organized topology. Hence, it thereby empowers itself to adapt to the optimal matching patterns between the paired features and reaches a sweet spot between model complexity and capability. Extensive experiments on cross-modal and two extra uni-modal retrieval tasks (image-text retrieval, person re-identification, fine-grained image retrieval) have validated its superiority and flexibility over various popular retrieval frameworks. More importantly, we further discover that it can be seamlessly incorporated into multiple application scenarios, and demonstrates promising prospects from Attention Mechanism to Knowledge Distillation in a plug-and-play manner. Our code is publicly available at: https://github.com/Paranioar/GSSF.

We introduce MRMR, the first expert-level multidisciplinary multimodal retrieval benchmark requiring intensive reasoning. MRMR contains 1,502 queries spanning 23 domains, with positive documents carefully verified by human experts. Compared to prior benchmarks, MRMR introduces three key advancements. First, it challenges retrieval systems across diverse areas of expertise, enabling fine-grained model comparison across domains. Second, queries are reasoning-intensive, with images requiring deeper interpretation such as diagnosing microscopic slides. We further introduce Contradiction Retrieval, a novel task requiring models to identify conflicting concepts. Finally, queries and documents are constructed as image-text interleaved sequences. Unlike earlier benchmarks restricted to single images or unimodal documents, MRMR offers a realistic setting with multi-image queries and mixed-modality corpus documents. We conduct an extensive evaluation of 4 categories of multimodal retrieval systems and 14 frontier models on MRMR. The text embedding model Qwen3-Embedding with LLM-generated image captions achieves the highest performance, highlighting substantial room for improving multimodal retrieval models. Although latest multimodal models such as Ops-MM-Embedding perform competitively on expert-domain queries, they fall short on reasoning-intensive tasks. We believe that MRMR paves the way for advancing multimodal retrieval in more realistic and challenging scenarios.

The Platonic Representation Hypothesis suggests that independently trained neural networks converge to increasingly similar latent spaces. However, current strategies for mapping these representations are inherently pairwise, scaling quadratically with the number of models and failing to yield a consistent global reference. In this paper, we study the alignment of M ge 3 models. We first adapt Generalized Procrustes Analysis (GPA) to construct a shared orthogonal universe that preserves the internal geometry essential for tasks like model stitching. We then show that strict isometric alignment is suboptimal for retrieval, where agreement-maximizing methods like Canonical Correlation Analysis (CCA) typically prevail. To bridge this gap, we finally propose Geometry-Corrected Procrustes Alignment (GCPA), which establishes a robust GPA-based universe followed by a post-hoc correction for directional mismatch. Extensive experiments demonstrate that GCPA consistently improves any-to-any retrieval while retaining a practical shared reference space.

Multi-vector models, such as ColBERT, are a significant advancement in neural information retrieval (IR), delivering state-of-the-art performance by representing queries and documents by multiple contextualized token-level embeddings. However, this increased representation size introduces considerable storage and computational overheads which have hindered widespread adoption in practice. A common approach to mitigate this overhead is to cluster the model's frozen vectors, but this strategy's effectiveness is fundamentally limited by the intrinsic clusterability of these embeddings. In this work, we introduce CRISP (Clustered Representations with Intrinsic Structure Pruning), a novel multi-vector training method which learns inherently clusterable representations directly within the end-to-end training process. By integrating clustering into the training phase rather than imposing it post-hoc, CRISP significantly outperforms post-hoc clustering at all representation sizes, as well as other token pruning methods. On the BEIR retrieval benchmarks, CRISP achieves a significant rate of ~3x reduction in the number of vectors while outperforming the original unpruned model. This indicates that learned clustering effectively denoises the model by filtering irrelevant information, thereby generating more robust multi-vector representations. With more aggressive clustering, CRISP achieves an 11x reduction in the number of vectors with only a 3.6% quality loss.

Discrete diffusion or flow models could enable faster and more controllable sequence generation than autoregressive models. We show that na\"ive linear flow matching on the simplex is insufficient toward this goal since it suffers from discontinuities in the training target and further pathologies. To overcome this, we develop Dirichlet flow matching on the simplex based on mixtures of Dirichlet distributions as probability paths. In this framework, we derive a connection between the mixtures' scores and the flow's vector field that allows for classifier and classifier-free guidance. Further, we provide distilled Dirichlet flow matching, which enables one-step sequence generation with minimal performance hits, resulting in O(L) speedups compared to autoregressive models. On complex DNA sequence generation tasks, we demonstrate superior performance compared to all baselines in distributional metrics and in achieving desired design targets for generated sequences. Finally, we show that our classifier-free guidance approach improves unconditional generation and is effective for generating DNA that satisfies design targets. Code is available at https://github.com/HannesStark/dirichlet-flow-matching.

Virtual immunohistochemistry (IHC) staining from hematoxylin and eosin (H&E) images can accelerate diagnostics by providing preliminary molecular insight directly from routine sections, reducing the need for repeat sectioning when tissue is limited. Existing methods improve realism through contrastive objectives, prototype matching, or domain alignment, yet the generator itself receives no direct guidance from pathology foundation models. We present UNIStainNet, a SPADE-UNet conditioned on dense spatial tokens from a frozen pathology foundation model (UNI), providing tissue-level semantic guidance for stain translation. A misalignment-aware loss suite preserves stain quantification accuracy, and learned stain embeddings enable a single model to serve multiple IHC markers simultaneously. On MIST, UNIStainNet achieves state-of-the-art distributional metrics on all four stains (HER2, Ki67, ER, PR) from a single unified model, where prior methods typically train separate per-stain models. On BCI, it also achieves the best distributional metrics. A tissue-type stratified failure analysis reveals that remaining errors are systematic, concentrating in non-tumor tissue. Code is available at https://github.com/facevoid/UNIStainNet.

Keypoint detection & descriptors are foundational tech-nologies for computer vision tasks like image matching, 3D reconstruction and visual odometry. Hand-engineered methods like Harris corners, SIFT, and HOG descriptors have been used for decades; more recently, there has been a trend to introduce learning in an attempt to improve keypoint detectors. On inspection however, the results are difficult to interpret; recent learning-based methods employ a vast diversity of experimental setups and design choices: empirical results are often reported using different backbones, protocols, datasets, types of supervisions or tasks. Since these differences are often coupled together, it raises a natural question on what makes a good learned keypoint detector. In this work, we revisit the design of existing keypoint detectors by deconstructing their methodologies and identifying the key components. We re-design each component from first-principle and propose Simple Learned Keypoints (SiLK) that is fully-differentiable, lightweight, and flexible. Despite its simplicity, SiLK advances new state-of-the-art on Detection Repeatability and Homography Estimation tasks on HPatches and 3D Point-Cloud Registration task on ScanNet, and achieves competitive performance to state-of-the-art on camera pose estimation in 2022 Image Matching Challenge and ScanNet.

Predicting protein function from sequence is a central challenge in computational biology. While existing methods rely heavily on structured ontologies or similarity-based techniques, they often lack the flexibility to express structure-free functional descriptions and novel biological functions. In this work, we introduce Prot2Text-V2, a novel multimodal sequence-to-text model that generates free-form natural language descriptions of protein function directly from amino acid sequences. Our method combines a protein language model as a sequence encoder (ESM-3B) and a decoder-only language model (LLaMA-3.1-8B-Instruct) through a lightweight nonlinear modality projector. A key innovation is our Hybrid Sequence-level Contrastive Alignment Learning (H-SCALE), which improves cross-modal learning by matching mean- and std-pooled protein embeddings with text representations via contrastive loss. After the alignment phase, we apply instruction-based fine-tuning using LoRA on the decoder to teach the model how to generate accurate protein function descriptions conditioned on the protein sequence. We train Prot2Text-V2 on about 250K curated entries from SwissProt and evaluate it under low-homology conditions, where test sequences have low similarity with training samples. Prot2Text-V2 consistently outperforms traditional and LLM-based baselines across various metrics.

Multimodal learning has revolutionized general domain tasks, yet its application in scientific discovery is hindered by the profound semantic gap between complex scientific imagery and sparse textual descriptions. We present S1-MMAlign, a large-scale, multi-disciplinary multimodal dataset comprising over 15.5 million high-quality image-text pairs derived from 2.5 million open-access scientific papers. Spanning disciplines from physics and biology to engineering, the dataset captures diverse visual modalities including experimental setups, heatmaps, and microscopic imagery. To address the pervasive issue of weak alignment in raw scientific captions, we introduce an AI-ready semantic enhancement pipeline that utilizes the Qwen-VL multimodal large model series to recaption images by synthesizing context from paper abstracts and citation contexts. Technical validation demonstrates that this enhancement significantly improves data quality: SciBERT-based pseudo-perplexity metrics show reduced semantic ambiguity, while CLIP scores indicate an 18.21% improvement in image-text alignment. S1-MMAlign provides a foundational resource for advancing scientific reasoning and cross-modal understanding in the era of AI for Science. The dataset is publicly available at https://huggingface.co/datasets/ScienceOne-AI/S1-MMAlign.

Pre-trained LLMs have demonstrated substantial capabilities across a range of conventional natural language processing (NLP) tasks, such as summarization and entity recognition. In this paper, we explore the application of LLMs in the generation of high-quality protein sequences. Specifically, we adopt a suite of pre-trained LLMs, including Mistral-7B1, Llama-2-7B2, Llama-3-8B3, and gemma-7B4, to produce valid protein sequences. All of these models are publicly available.5 Unlike previous work in this field, our approach utilizes a relatively small dataset comprising 42,000 distinct human protein sequences. We retrain these models to process protein-related data, ensuring the generation of biologically feasible protein structures. Our findings demonstrate that even with limited data, the adapted models exhibit efficiency comparable to established protein-focused models such as ProGen varieties, ProtGPT2, and ProLLaMA, which were trained on millions of protein sequences. To validate and quantify the performance of our models, we conduct comparative analyses employing standard metrics such as pLDDT, RMSD, TM-score, and REU. Furthermore, we commit to making the trained versions of all four models publicly available, fostering greater transparency and collaboration in the field of computational biology.

Optical Chemical Structure Recognition (OCSR) is crucial for digitizing chemical knowledge by converting molecular images into machine-readable formats. While recent vision-language models (VLMs) have shown potential in this task, their image-captioning approach often struggles with complex molecular structures and inconsistent annotations. To overcome these challenges, we introduce GTR-Mol-VLM, a novel framework featuring two key innovations: (1) the Graph Traversal as Visual Chain of Thought mechanism that emulates human reasoning by incrementally parsing molecular graphs through sequential atom-bond predictions, and (2) the data-centric principle of Faithfully Recognize What You've Seen, which addresses the mismatch between abbreviated structures in images and their expanded annotations. To support model development, we constructed GTR-CoT-1.3M, a large-scale instruction-tuning dataset with meticulously corrected annotations, and introduced MolRec-Bench, the first benchmark designed for a fine-grained evaluation of graph-parsing accuracy in OCSR. Comprehensive experiments demonstrate that GTR-Mol-VLM achieves superior results compared to specialist models, chemistry-domain VLMs, and commercial general-purpose VLMs. Notably, in scenarios involving molecular images with functional group abbreviations, GTR-Mol-VLM outperforms the second-best baseline by approximately 14 percentage points, both in SMILES-based and graph-based metrics. We hope that this work will drive OCSR technology to more effectively meet real-world needs, thereby advancing the fields of cheminformatics and AI for Science. We will release GTR-CoT at https://github.com/opendatalab/GTR-CoT.

Protein function prediction is a crucial task in bioinformatics, with significant implications for understanding biological processes and disease mechanisms. While the relationship between sequence and function has been extensively explored, translating protein structure to function continues to present substantial challenges. Various models, particularly, CNN and graph-based deep learning approaches that integrate structural and functional data, have been proposed to address these challenges. However, these methods often fall short in elucidating the functional significance of key residues essential for protein functionality, as they predominantly adopt a retrospective perspective, leading to suboptimal performance. Inspired by region proposal networks in computer vision, we introduce the Protein Region Proposal Network (ProteinRPN) for accurate protein function prediction. Specifically, the region proposal module component of ProteinRPN identifies potential functional regions (anchors) which are refined through the hierarchy-aware node drop pooling layer favoring nodes with defined secondary structures and spatial proximity. The representations of the predicted functional nodes are enriched using attention mechanisms and subsequently fed into a Graph Multiset Transformer, which is trained with supervised contrastive (SupCon) and InfoNCE losses on perturbed protein structures. Our model demonstrates significant improvements in predicting Gene Ontology (GO) terms, effectively localizing functional residues within protein structures. The proposed framework provides a robust, scalable solution for protein function annotation, advancing the understanding of protein structure-function relationships in computational biology.

Joint Alignment (JA) of images aims to align a collection of images into a unified coordinate frame, such that semantically-similar features appear at corresponding spatial locations. Most existing approaches often require long training times, large-capacity models, and extensive hyperparameter tuning. We introduce FastJAM, a rapid, graph-based method that drastically reduces the computational complexity of joint alignment tasks. FastJAM leverages pairwise matches computed by an off-the-shelf image matcher, together with a rapid nonparametric clustering, to construct a graph representing intra- and inter-image keypoint relations. A graph neural network propagates and aggregates these correspondences, efficiently predicting per-image homography parameters via image-level pooling. Utilizing an inverse-compositional loss, that eliminates the need for a regularization term over the predicted transformations (and thus also obviates the hyperparameter tuning associated with such terms), FastJAM performs image JA quickly and effectively. Experimental results on several benchmarks demonstrate that FastJAM achieves results better than existing modern JA methods in terms of alignment quality, while reducing computation time from hours or minutes to mere seconds. Our code is available at our project webpage, https://bgu-cs-vil.github.io/FastJAM/

General-purpose foundation models have become increasingly important in the field of artificial intelligence. While self-supervised learning (SSL) and Masked Image Modeling (MIM) have led to promising results in building such foundation models for remote sensing, these models primarily learn low-level features, require annotated data for fine-tuning, and not applicable for retrieval and zero-shot applications due to the lack of language understanding. In response to these limitations, we propose RemoteCLIP, the first vision-language foundation model for remote sensing that aims to learn robust visual features with rich semantics, as well as aligned text embeddings for seamless downstream application. To address the scarcity of pre-training data, we leverage data scaling, converting heterogeneous annotations based on Box-to-Caption (B2C) and Mask-to-Box (M2B) conversion, and further incorporating UAV imagery, resulting a 12xlarger pretraining dataset. RemoteCLIP can be applied to a variety of downstream tasks, including zero-shot image classification, linear probing, k-NN classification, few-shot classification, image-text retrieval, and object counting. Evaluations on 16 datasets, including a newly introduced RemoteCount benchmark to test the object counting ability, show that RemoteCLIP consistently outperforms baseline foundation models across different model scales. Impressively, RemoteCLIP outperform previous SoTA by 9.14% mean recall on RSICD dataset and by 8.92% on RSICD dataset. For zero-shot classification, our RemoteCLIP outperform CLIP baseline by up to 6.39% average accuracy on 12 downstream datasets.

The growing interest in machine learning problems over graphs with additional node information such as texts, images, or labels has popularized methods that require the costly operation of processing the entire graph. Yet, little effort has been made to the development of fast local methods (i.e. without accessing the entire graph) that extract useful information from such data. To that end, we propose a study of local graph clustering using noisy node labels as a proxy for additional node information. In this setting, nodes receive initial binary labels based on cluster affiliation: 1 if they belong to the target cluster and 0 otherwise. Subsequently, a fraction of these labels is flipped. We investigate the benefits of incorporating noisy labels for local graph clustering. By constructing a weighted graph with such labels, we study the performance of graph diffusion-based local clustering method on both the original and the weighted graphs. From a theoretical perspective, we consider recovering an unknown target cluster with a single seed node in a random graph with independent noisy node labels. We provide sufficient conditions on the label noise under which, with high probability, using diffusion in the weighted graph yields a more accurate recovery of the target cluster. This approach proves more effective than using the given labels alone or using diffusion in the label-free original graph. Empirically, we show that reliable node labels can be obtained with just a few samples from an attributed graph. Moreover, utilizing these labels via diffusion in the weighted graph leads to significantly better local clustering performance across several real-world datasets, improving F1 scores by up to 13%.

Modern large language models (LLMs) such as GPT, Claude, and Gemini have transformed the way we learn, work, and communicate. Yet, their ability to produce highly human-like text raises serious concerns about misinformation and academic integrity, making it an urgent need for reliable algorithms to detect LLM-generated content. In this paper, we start by presenting a geometric approach to demystify rewrite-based detection algorithms, revealing their underlying rationale and demonstrating their generalization ability. Building on this insight, we introduce a novel rewrite-based detection algorithm that adaptively learns the distance between the original and rewritten text. Theoretically, we demonstrate that employing an adaptively learned distance function is more effective for detection than using a fixed distance. Empirically, we conduct extensive experiments with over 100 settings, and find that our approach demonstrates superior performance over baseline algorithms in the majority of scenarios. In particular, it achieves relative improvements from 57.8\% to 80.6\% over the strongest baseline across different target LLMs (e.g., GPT, Claude, and Gemini).

Table Structure Recognition (TSR) is vital for various downstream tasks like information retrieval, table reconstruction, and document understanding. While most state-of-the-art (SOTA) research predominantly focuses on TSR in English documents, the need for similar capabilities in other languages is evident, considering the global diversity of data. Moreover, creating substantial labeled data in non-English languages and training these SOTA models from scratch is costly and time-consuming. We propose TSR as a language-agnostic cell arrangement prediction and introduce SPRINT, Script-agnostic Structure Recognition in Tables. SPRINT uses recently introduced Optimized Table Structure Language (OTSL) sequences to predict table structures. We show that when coupled with a pre-trained table grid estimator, SPRINT can improve the overall tree edit distance-based similarity structure scores of tables even for non-English documents. We experimentally evaluate our performance across benchmark TSR datasets including PubTabNet, FinTabNet, and PubTables-1M. Our findings reveal that SPRINT not only matches SOTA models in performance on standard datasets but also demonstrates lower latency. Additionally, SPRINT excels in accurately identifying table structures in non-English documents, surpassing current leading models by showing an absolute average increase of 11.12%. We also present an algorithm for converting valid OTSL predictions into a widely used HTML-based table representation. To encourage further research, we release our code and Multilingual Scanned and Scene Table Structure Recognition Dataset, MUSTARD labeled with OTSL sequences for 1428 tables in thirteen languages encompassing several scripts at https://github.com/IITB-LEAP-OCR/SPRINT

We introduce InternAgent-1.5, a unified system designed for end-to-end scientific discovery across computational and empirical domains. The system is built on a structured architecture composed of three coordinated subsystems for generation, verification, and evolution. These subsystems are supported by foundational capabilities for deep research, solution optimization, and long horizon memory. The architecture allows InternAgent-1.5 to operate continuously across extended discovery cycles while maintaining coherent and improving behavior. It also enables the system to coordinate computational modeling and laboratory experimentation within a single unified system. We evaluate InternAgent-1.5 on scientific reasoning benchmarks such as GAIA, HLE, GPQA, and FrontierScience, and the system achieves leading performance that demonstrates strong foundational capabilities. Beyond these benchmarks, we further assess two categories of discovery tasks. In algorithm discovery tasks, InternAgent-1.5 autonomously designs competitive methods for core machine learning problems. In empirical discovery tasks, it executes complete computational or wet lab experiments and produces scientific findings in earth, life, biological, and physical domains. Overall, these results show that InternAgent-1.5 provides a general and scalable framework for autonomous scientific discovery.

In this article, we introduce a new parameterized family of topological invariants, taking the form of candidate decompositions, for multi-parameter persistence modules. We prove that our candidate decompositions are controllable approximations: when restricting to modules that can be decomposed into interval summands, we establish theoretical results about the approximation error between our candidate decompositions and the true underlying module in terms of the standard interleaving and bottleneck distances. Moreover, even when the underlying module does not admit such a decomposition, our candidate decompositions are nonetheless stable invariants; small perturbations in the underlying module lead to small perturbations in the candidate decomposition. Then, we introduce MMA (Multipersistence Module Approximation): an algorithm for computing stable instances of such invariants, which is based on fibered barcodes and exact matchings, two constructions that stem from the theory of single-parameter persistence. By design, MMA can handle an arbitrary number of filtrations, and has bounded complexity and running time. Finally, we present empirical evidence validating the generalization capabilities and running time speed-ups of MMA on several data sets.

While global point cloud registration systems have advanced significantly in all aspects, many studies have focused on specific components, such as feature extraction, graph-theoretic pruning, or pose solvers. In this paper, we take a holistic view on the registration problem and develop an open-source and versatile C++ library for point cloud registration, called KISS-Matcher. KISS-Matcher combines a novel feature detector, Faster-PFH, that improves over the classical fast point feature histogram (FPFH). Moreover, it adopts a k-core-based graph-theoretic pruning to reduce the time complexity of rejecting outlier correspondences. Finally, it combines these modules in a complete, user-friendly, and ready-to-use pipeline. As verified by extensive experiments, KISS-Matcher has superior scalability and broad applicability, achieving a substantial speed-up compared to state-of-the-art outlier-robust registration pipelines while preserving accuracy. Our code will be available at https://github.com/MIT-SPARK/KISS-Matcher.

Retrieval-Augmented Generation (RAG) systems are increasingly vital for navigating the ever-expanding body of scientific literature, particularly in high-stakes domains such as chemistry. Despite the promise of RAG, foundational design choices -- such as how documents are segmented and represented -- remain underexplored in domain-specific contexts. This study presents the first large-scale, systematic evaluation of chunking strategies and embedding models tailored to chemistry-focused RAG systems. We investigate 25 chunking configurations across five method families and evaluate 48 embedding models on three chemistry-specific benchmarks, including the newly introduced QuestChemRetrieval dataset. Our results reveal that recursive token-based chunking (specifically R100-0) consistently outperforms other approaches, offering strong performance with minimal resource overhead. We also find that retrieval-optimized embeddings -- such as Nomic and Intfloat E5 variants -- substantially outperform domain-specialized models like SciBERT. By releasing our datasets, evaluation framework, and empirical benchmarks, we provide actionable guidelines for building effective and efficient chemistry-aware RAG systems.

Recent advancements in biological research leverage the integration of molecules, proteins, and natural language to enhance drug discovery. However, current models exhibit several limitations, such as the generation of invalid molecular SMILES, underutilization of contextual information, and equal treatment of structured and unstructured knowledge. To address these issues, we propose BioT5, a comprehensive pre-training framework that enriches cross-modal integration in biology with chemical knowledge and natural language associations. BioT5 utilizes SELFIES for 100% robust molecular representations and extracts knowledge from the surrounding context of bio-entities in unstructured biological literature. Furthermore, BioT5 distinguishes between structured and unstructured knowledge, leading to more effective utilization of information. After fine-tuning, BioT5 shows superior performance across a wide range of tasks, demonstrating its strong capability of capturing underlying relations and properties of bio-entities. Our code is available at https://github.com/QizhiPei/BioT5{Github}.

The automatic analysis of chemical literature has immense potential to accelerate the discovery of new materials and drugs. Much of the critical information in patent documents and scientific articles is contained in figures, depicting the molecule structures. However, automatically parsing the exact chemical structure is a formidable challenge, due to the amount of detailed information, the diversity of drawing styles, and the need for training data. In this work, we introduce MolGrapher to recognize chemical structures visually. First, a deep keypoint detector detects the atoms. Second, we treat all candidate atoms and bonds as nodes and put them in a graph. This construct allows a natural graph representation of the molecule. Last, we classify atom and bond nodes in the graph with a Graph Neural Network. To address the lack of real training data, we propose a synthetic data generation pipeline producing diverse and realistic results. In addition, we introduce a large-scale benchmark of annotated real molecule images, USPTO-30K, to spur research on this critical topic. Extensive experiments on five datasets show that our approach significantly outperforms classical and learning-based methods in most settings. Code, models, and datasets are available.

We present FastRP, a scalable and performant algorithm for learning distributed node representations in a graph. FastRP is over 4,000 times faster than state-of-the-art methods such as DeepWalk and node2vec, while achieving comparable or even better performance as evaluated on several real-world networks on various downstream tasks. We observe that most network embedding methods consist of two components: construct a node similarity matrix and then apply dimension reduction techniques to this matrix. We show that the success of these methods should be attributed to the proper construction of this similarity matrix, rather than the dimension reduction method employed. FastRP is proposed as a scalable algorithm for network embeddings. Two key features of FastRP are: 1) it explicitly constructs a node similarity matrix that captures transitive relationships in a graph and normalizes matrix entries based on node degrees; 2) it utilizes very sparse random projection, which is a scalable optimization-free method for dimension reduction. An extra benefit from combining these two design choices is that it allows the iterative computation of node embeddings so that the similarity matrix need not be explicitly constructed, which further speeds up FastRP. FastRP is also advantageous for its ease of implementation, parallelization and hyperparameter tuning. The source code is available at https://github.com/GTmac/FastRP.

Image segmentation is a largely researched field where neural networks find vast applications in many facets of technology. Some of the most popular approaches to train segmentation networks employ loss functions optimizing pixel-overlap, an objective that is insufficient for many segmentation tasks. In recent years, their limitations fueled a growing interest in topology-aware methods, which aim to recover the correct topology of the segmented structures. However, so far, none of the existing approaches achieve a spatially correct matching between the topological features of ground truth and prediction. In this work, we propose the first topologically and feature-wise accurate metric and loss function for supervised image segmentation, which we term Betti matching. We show how induced matchings guarantee the spatially correct matching between barcodes in a segmentation setting. Furthermore, we propose an efficient algorithm to compute the Betti matching of images. We show that the Betti matching error is an interpretable metric to evaluate the topological correctness of segmentations, which is more sensitive than the well-established Betti number error. Moreover, the differentiability of the Betti matching loss enables its use as a loss function. It improves the topological performance of segmentation networks across six diverse datasets while preserving the volumetric performance. Our code is available in https://github.com/nstucki/Betti-matching.

Recently, extensive deep learning architectures and pretraining strategies have been explored to support downstream protein applications. Additionally, domain-specific models incorporating biological knowledge have been developed to enhance performance in specialized tasks. In this work, we introduce Protap, a comprehensive benchmark that systematically compares backbone architectures, pretraining strategies, and domain-specific models across diverse and realistic downstream protein applications. Specifically, Protap covers five applications: three general tasks and two novel specialized tasks, i.e., enzyme-catalyzed protein cleavage site prediction and targeted protein degradation, which are industrially relevant yet missing from existing benchmarks. For each application, Protap compares various domain-specific models and general architectures under multiple pretraining settings. Our empirical studies imply that: (i) Though large-scale pretraining encoders achieve great results, they often underperform supervised encoders trained on small downstream training sets. (ii) Incorporating structural information during downstream fine-tuning can match or even outperform protein language models pretrained on large-scale sequence corpora. (iii) Domain-specific biological priors can enhance performance on specialized downstream tasks. Code and datasets are publicly available at https://github.com/Trust-App-AI-Lab/protap.

Molecule discovery serves as a cornerstone in numerous scientific domains, fueling the development of new materials and innovative drug designs. Recent developments of in-silico molecule discovery have highlighted the promising results of cross-modal techniques, which bridge molecular structures with their descriptive annotations. However, these cross-modal methods frequently encounter the issue of data scarcity, hampering their performance and application. In this paper, we address the low-resource challenge by utilizing artificially-real data generated by Large Language Models (LLMs). We first introduce a retrieval-based prompting strategy to construct high-quality pseudo data, then explore the optimal method to effectively leverage this pseudo data. Experiments show that using pseudo data for domain adaptation outperforms all existing methods, while also requiring a smaller model scale, reduced data size and lower training cost, highlighting its efficiency. Furthermore, our method shows a sustained improvement as the volume of pseudo data increases, revealing the great potential of pseudo data in advancing low-resource cross-modal molecule discovery.

Matched molecular pairs (MMPs) capture the local chemical edits that medicinal chemists routinely use to design analogs, but existing ML approaches either operate at the whole-molecule level with limited edit controllability or learn MMP-style edits from restricted settings and small models. We propose a variable-to-variable formulation of analog generation and train a foundation model on large-scale MMP transformations (MMPTs) to generate diverse variables conditioned on an input variable. To enable practical control, we develop prompting mechanisms that let the users specify preferred transformation patterns during generation. We further introduce MMPT-RAG, a retrieval-augmented framework that uses external reference analogs as contextual guidance to steer generation and generalize from project-specific series. Experiments on general chemical corpora and patent-specific datasets demonstrate improved diversity, novelty, and controllability, and show that our method recovers realistic analog structures in practical discovery scenarios.

Molecule discovery is a pivotal research field, impacting everything from the medicines we take to the materials we use. Recently, Large Language Models (LLMs) have been widely adopted in molecule understanding and generation, yet the alignments between molecules and their corresponding captions remain a significant challenge. Previous endeavours often treat the molecule as a general SMILES string or molecular graph, neglecting the fine-grained alignments between the molecular sub-structures and the descriptive textual phrases, which are crucial for accurate and explainable predictions. In this case, we introduce MolReFlect, a novel teacher-student framework designed to contextually perform the molecule-caption alignments in a fine-grained way. Our approach initially leverages a larger teacher LLM to label the detailed alignments by directly extracting critical phrases from molecule captions or SMILES strings and implying them to corresponding sub-structures or characteristics. To refine these alignments, we propose In-Context Selective Reflection, which retrieves previous extraction results as context examples for teacher LLM to reflect and lets a smaller student LLM select from in-context reflection and previous extraction results. Finally, we enhance the learning process of the student LLM through Chain-of-Thought In-Context Molecule Tuning, integrating the fine-grained alignments and the reasoning processes within the Chain-of-Thought format. Our experimental results demonstrate that MolReFlect enables LLMs like Mistral-7B to significantly outperform the previous baselines, achieving SOTA performance on the ChEBI-20 dataset. This advancement not only enhances the generative capabilities of LLMs in the molecule-caption translation task, but also contributes to a more explainable framework.

Vector Similarity Search (VSS) in high-dimensional spaces is rapidly emerging as core functionality in next-generation database systems for numerous data-intensive services -- from embedding lookups in large language models (LLMs), to semantic information retrieval and recommendation engines. Current benchmarks, however, evaluate VSS primarily on the recall-latency trade-off against a ground truth defined solely by distance metrics, neglecting how retrieval quality ultimately impacts downstream tasks. This disconnect can mislead both academic research and industrial practice. We present Iceberg, a holistic benchmark suite for end-to-end evaluation of VSS methods in realistic application contexts. From a task-centric view, Iceberg uncovers the Information Loss Funnel, which identifies three principal sources of end-to-end performance degradation: (1) Embedding Loss during feature extraction; (2) Metric Misuse, where distances poorly reflect task relevance; (3) Data Distribution Sensitivity, highlighting index robustness across skews and modalities. For a more comprehensive assessment, Iceberg spans eight diverse datasets across key domains such as image classification, face recognition, text retrieval, and recommendation systems. Each dataset, ranging from 1M to 100M vectors, includes rich, task-specific labels and evaluation metrics, enabling assessment of retrieval algorithms within the full application pipeline rather than in isolation. Iceberg benchmarks 13 state-of-the-art VSS methods and re-ranks them based on application-level metrics, revealing substantial deviations from traditional rankings derived purely from recall-latency evaluations. Building on these insights, we define a set of task-centric meta-features and derive an interpretable decision tree to guide practitioners in selecting and tuning VSS methods for their specific workloads.

The vast, complex, and dynamic nature of social message data has posed challenges to social event detection (SED). Despite considerable effort, these challenges persist, often resulting in inadequately expressive message representations (ineffective) and prolonged learning durations (inefficient). In response to the challenges, this work introduces an unsupervised framework, HyperSED (Hyperbolic SED). Specifically, the proposed framework first models social messages into semantic-based message anchors, and then leverages the structure of the anchor graph and the expressiveness of the hyperbolic space to acquire structure- and geometry-aware anchor representations. Finally, HyperSED builds the partitioning tree of the anchor message graph by incorporating differentiable structural information as the reflection of the detected events. Extensive experiments on public datasets demonstrate HyperSED's competitive performance, along with a substantial improvement in efficiency compared to the current state-of-the-art unsupervised paradigm. Statistically, HyperSED boosts incremental SED by an average of 2%, 2%, and 25% in NMI, AMI, and ARI, respectively; enhancing efficiency by up to 37.41 times and at least 12.10 times, illustrating the advancement of the proposed framework. Our code is publicly available at https://github.com/XiaoyanWork/HyperSED.

The astonishing breakthrough of multimodal large language models (MLLMs) has necessitated new benchmarks to quantitatively assess their capabilities, reveal their limitations, and indicate future research directions. However, this is challenging in the context of remote sensing (RS), since the imagery features ultra-high resolution that incorporates extremely complex semantic relationships. Existing benchmarks usually adopt notably smaller image sizes than real-world RS scenarios, suffer from limited annotation quality, and consider insufficient dimensions of evaluation. To address these issues, we present XLRS-Bench: a comprehensive benchmark for evaluating the perception and reasoning capabilities of MLLMs in ultra-high-resolution RS scenarios. XLRS-Bench boasts the largest average image size (8500times8500) observed thus far, with all evaluation samples meticulously annotated manually, assisted by a novel semi-automatic captioner on ultra-high-resolution RS images. On top of the XLRS-Bench, 16 sub-tasks are defined to evaluate MLLMs' 10 kinds of perceptual capabilities and 6 kinds of reasoning capabilities, with a primary emphasis on advanced cognitive processes that facilitate real-world decision-making and the capture of spatiotemporal changes. The results of both general and RS-focused MLLMs on XLRS-Bench indicate that further efforts are needed for real-world RS applications. We have open-sourced XLRS-Bench to support further research in developing more powerful MLLMs for remote sensing.

Despite the impressive advancements of Large Language Models (LLMs) in generating text, they are often limited by the knowledge contained in the input and prone to producing inaccurate or hallucinated content. To tackle these issues, Retrieval-augmented Generation (RAG) is employed as an effective strategy to enhance the available knowledge base and anchor the responses in reality by pulling additional texts from external databases. In real-world applications, texts are often linked through entities within a graph, such as citations in academic papers or comments in social networks. This paper exploits these topological relationships to guide the retrieval process in RAG. Specifically, we explore two kinds of topological connections: proximity-based, focusing on closely connected nodes, and role-based, which looks at nodes sharing similar subgraph structures. Our empirical research confirms their relevance to text relationships, leading us to develop a Topology-aware Retrieval-augmented Generation framework. This framework includes a retrieval module that selects texts based on their topological relationships and an aggregation module that integrates these texts into prompts to stimulate LLMs for text generation. We have curated established text-attributed networks and conducted comprehensive experiments to validate the effectiveness of this framework, demonstrating its potential to enhance RAG with topological awareness.

Small-molecule identification from tandem mass spectrometry (MS/MS) remains a bottleneck in untargeted settings where spectral libraries are incomplete. While deep learning offers a solution, current approaches typically fall into two extremes: explicit generative models that construct molecular graphs atom-by-atom, or joint contrastive models that learn cross-modal subspaces from scratch. We introduce SpecBridge, a novel implicit alignment framework that treats structure identification as a geometric alignment problem. SpecBridge fine-tunes a self-supervised spectral encoder (DreaMS) to project directly into the latent space of a frozen molecular foundation model (ChemBERTa), and then performs retrieval by cosine similarity to a fixed bank of precomputed molecular embeddings. Across MassSpecGym, Spectraverse, and MSnLib benchmarks, SpecBridge improves top-1 retrieval accuracy by roughly 20-25% relative to strong neural baselines, while keeping the number of trainable parameters small. These results suggest that aligning to frozen foundation models is a practical, stable alternative to designing new architectures from scratch. The code for SpecBridge is released at https://github.com/HassounLab/SpecBridge.

Motivation: Phenotype concept recognition (CR) is a fundamental task in biomedical text mining. However, existing methods either require ontology-specific training, making them struggle to generalize across diverse text styles and evolving biomedical terminology, or depend on general-purpose large language models (LLMs) that lack necessary domain knowledge. Results: To address these limitations, we propose AutoPCR, a prompt-based phenotype CR method designed to automatically generalize to new ontologies and unseen data without ontology-specific training. To further boost performance, we also introduce an optional self-supervised training strategy. Experiments show that AutoPCR achieves the best average and most robust performance across datasets. Further ablation and transfer studies demonstrate its inductive capability and generalizability to new ontologies. Availability and Implementation: Our code is available at https://github.com/yctao7/AutoPCR. Contact: drjieliu@umich.edu

Pre-trained large language models demonstrate potential in extracting information from DNA sequences, yet adapting to a variety of tasks and data modalities remains a challenge. To address this, we propose DNAGPT, a generalized DNA pre-training model trained on over 200 billion base pairs from all mammals. By enhancing the classic GPT model with a binary classification task (DNA sequence order), a numerical regression task (guanine-cytosine content prediction), and a comprehensive token language, DNAGPT can handle versatile DNA analysis tasks while processing both sequence and numerical data. Our evaluation of genomic signal and region recognition, mRNA abundance regression, and artificial genomes generation tasks demonstrates DNAGPT's superior performance compared to existing models designed for specific downstream tasks, benefiting from pre-training using the newly designed model structure.

We propose a novel end-to-end document understanding model called SeRum (SElective Region Understanding Model) for extracting meaningful information from document images, including document analysis, retrieval, and office automation. Unlike state-of-the-art approaches that rely on multi-stage technical schemes and are computationally expensive, SeRum converts document image understanding and recognition tasks into a local decoding process of the visual tokens of interest, using a content-aware token merge module. This mechanism enables the model to pay more attention to regions of interest generated by the query decoder, improving the model's effectiveness and speeding up the decoding speed of the generative scheme. We also designed several pre-training tasks to enhance the understanding and local awareness of the model. Experimental results demonstrate that SeRum achieves state-of-the-art performance on document understanding tasks and competitive results on text spotting tasks. SeRum represents a substantial advancement towards enabling efficient and effective end-to-end document understanding.