Daily Papers

Human body actions are an important form of non-verbal communication in social interactions. This paper focuses on a specific subset of body actions known as micro-actions, which are subtle, low-intensity body movements that provide a deeper understanding of inner human feelings. In real-world scenarios, human micro-actions often co-occur, with multiple micro-actions overlapping in time, such as simultaneous head and hand movements. However, current research primarily focuses on recognizing individual micro-actions while overlooking their co-occurring nature. To narrow this gap, we propose a new task named Multi-label Micro-Action Detection (MMAD), which involves identifying all micro-actions in a given short video, determining their start and end times, and categorizing them. Achieving this requires a model capable of accurately capturing both long-term and short-term action relationships to locate and classify multiple micro-actions. To support the MMAD task, we introduce a new dataset named Multi-label Micro-Action-52 (MMA-52), specifically designed to facilitate the detailed analysis and exploration of complex human micro-actions. The proposed MMA-52 dataset is available at: https://github.com/VUT-HFUT/Micro-Action.

Drug discovery typically consists of multiple steps, including identifying a target protein key to a disease's etiology, validating that interacting with this target could prevent symptoms or cure the disease, discovering a small molecule or biologic therapeutic to interact with it, and optimizing the candidate molecule through a complex landscape of required properties. Drug discovery related tasks often involve prediction and generation while considering multiple entities that potentially interact, which poses a challenge for typical AI models. For this purpose we present MAMMAL - Molecular Aligned Multi-Modal Architecture and Language - a method that we applied to create a versatile multi-task foundation model ibm/biomed.omics.bl.sm.ma-ted-458m that learns from large-scale biological datasets (2 billion samples) across diverse modalities, including proteins, small molecules, and genes. We introduce a prompt syntax that supports a wide range of classification, regression, and generation tasks. It allows combining different modalities and entity types as inputs and/or outputs. Our model handles combinations of tokens and scalars and enables the generation of small molecules and proteins, property prediction, and transcriptomic lab test predictions. We evaluated the model on 11 diverse downstream tasks spanning different steps within a typical drug discovery pipeline, where it reaches new SOTA in 9 tasks and is comparable to SOTA in 2 tasks. This performance is achieved while using a unified architecture serving all tasks, in contrast to the original SOTA performance achieved using tailored architectures. The model code and pretrained weights are publicly available at https://github.com/BiomedSciAI/biomed-multi-alignment and https://huggingface.co/ibm/biomed.omics.bl.sm.ma-ted-458m.

Accumulated clinical studies show that microbes living in humans interact closely with human hosts, and get involved in modulating drug efficacy and drug toxicity. Microbes have become novel targets for the development of antibacterial agents. Therefore, screening of microbe-drug associations can benefit greatly drug research and development. With the increase of microbial genomic and pharmacological datasets, we are greatly motivated to develop an effective computational method to identify new microbe-drug associations. In this paper, we proposed a novel method, Graph2MDA, to predict microbe-drug associations by using variational graph autoencoder (VGAE). We constructed multi-modal attributed graphs based on multiple features of microbes and drugs, such as molecular structures, microbe genetic sequences, and function annotations. Taking as input the multi-modal attribute graphs, VGAE was trained to learn the informative and interpretable latent representations of each node and the whole graph, and then a deep neural network classifier was used to predict microbe-drug associations. The hyperparameter analysis and model ablation studies showed the sensitivity and robustness of our model. We evaluated our method on three independent datasets and the experimental results showed that our proposed method outperformed six existing state-of-the-art methods. We also explored the meaningness of the learned latent representations of drugs and found that the drugs show obvious clustering patterns that are significantly consistent with drug ATC classification. Moreover, we conducted case studies on two microbes and two drugs and found 75\%-95\% predicted associations have been reported in PubMed literature. Our extensive performance evaluations validated the effectiveness of our proposed method.\

Micro-Actions (MAs) are an important form of non-verbal communication in social interactions, with potential applications in human emotional analysis. However, existing methods in Micro-Action Recognition often overlook the inherent subtle changes in MAs, which limits the accuracy of distinguishing MAs with subtle changes. To address this issue, we present a novel Motion-guided Modulation Network (MMN) that implicitly captures and modulates subtle motion cues to enhance spatial-temporal representation learning. Specifically, we introduce a Motion-guided Skeletal Modulation module (MSM) to inject motion cues at the skeletal level, acting as a control signal to guide spatial representation modeling. In parallel, we design a Motion-guided Temporal Modulation module (MTM) to incorporate motion information at the frame level, facilitating the modeling of holistic motion patterns in micro-actions. Finally, we propose a motion consistency learning strategy to aggregate the motion cues from multi-scale features for micro-action classification. Experimental results on the Micro-Action 52 and iMiGUE datasets demonstrate that MMN achieves state-of-the-art performance in skeleton-based micro-action recognition, underscoring the importance of explicitly modeling subtle motion cues. The code will be available at https://github.com/momiji-bit/MMN.

Micro-Action Recognition (MAR) has gained increasing attention due to its crucial role as a form of non-verbal communication in social interactions, with promising potential for applications in human communication and emotion analysis. However, current approaches often overlook the inherent ambiguity in micro-actions, which arises from the wide category range and subtle visual differences between categories. This oversight hampers the accuracy of micro-action recognition. In this paper, we propose a novel Prototypical Calibrating Ambiguous Network (PCAN) to unleash and mitigate the ambiguity of MAR. Firstly, we employ a hierarchical action-tree to identify the ambiguous sample, categorizing them into distinct sets of ambiguous samples of false negatives and false positives, considering both body- and action-level categories. Secondly, we implement an ambiguous contrastive refinement module to calibrate these ambiguous samples by regulating the distance between ambiguous samples and their corresponding prototypes. This calibration process aims to pull false negative (FN) samples closer to their respective prototypes and push false positive (FP) samples apart from their affiliated prototypes. In addition, we propose a new prototypical diversity amplification loss to strengthen the model's capacity by amplifying the differences between different prototypes. Finally, we propose a prototype-guided rectification to rectify prediction by incorporating the representability of prototypes. Extensive experiments conducted on the benchmark dataset demonstrate the superior performance of our method compared to existing approaches. The code is available at https://github.com/kunli-cs/PCAN.

Recent progress in Large Language Models (LLMs) has drawn attention to their potential for accelerating drug discovery. However, a central problem remains: translating theoretical ideas into robust implementations in the highly specialized context of pharmaceutical research. This limitation prevents practitioners from making full use of the latest AI developments in drug discovery. To address this challenge, we introduce DrugAgent, a multi-agent framework that automates machine learning (ML) programming for drug discovery tasks. DrugAgent employs an LLM Planner that formulates high-level ideas and an LLM Instructor that identifies and integrates domain knowledge when implementing those ideas. We present case studies on three representative drug discovery tasks. Our results show that DrugAgent consistently outperforms leading baselines, including a relative improvement of 4.92% in ROC-AUC compared to ReAct for drug-target interaction (DTI). DrugAgent is publicly available at https://anonymous.4open.science/r/drugagent-5C42/.

Spotting facial micro-expression from videos finds various potential applications in fields including clinical diagnosis and interrogation, meanwhile this task is still difficult due to the limited scale of training data. To solve this problem, this paper tries to formulate a new task called micro-expression generation and then presents a strong baseline which combines the first order motion model with facial prior knowledge. Given a target face, we intend to drive the face to generate micro-expression videos according to the motion patterns of source videos. Specifically, our new model involves three modules. First, we extract facial prior features from a region focusing module. Second, we estimate facial motion using key points and local affine transformations with a motion prediction module. Third, expression generation module is used to drive the target face to generate videos. We train our model on public CASME II, SAMM and SMIC datasets and then use the model to generate new micro-expression videos for evaluation. Our model achieves the first place in the Facial Micro-Expression Challenge 2021 (MEGC2021), where our superior performance is verified by three experts with Facial Action Coding System certification. Source code is provided in https://github.com/Necolizer/Facial-Prior-Based-FOMM.

Hit identification is a central challenge in early drug discovery, traditionally requiring substantial experimental resources. Recent advances in artificial intelligence, particularly large language models (LLMs), have enabled virtual screening methods that reduce costs and improve efficiency. However, the growing complexity of these tools has limited their accessibility to wet-lab researchers. Multi-agent systems offer a promising solution by combining the interpretability of LLMs with the precision of specialized models and tools. In this work, we present MADD, a multi-agent system that builds and executes customized hit identification pipelines from natural language queries. MADD employs four coordinated agents to handle key subtasks in de novo compound generation and screening. We evaluate MADD across seven drug discovery cases and demonstrate its superior performance compared to existing LLM-based solutions. Using MADD, we pioneer the application of AI-first drug design to five biological targets and release the identified hit molecules. Finally, we introduce a new benchmark of query-molecule pairs and docking scores for over three million compounds to contribute to the agentic future of drug design.

Recent advances in large language models have demonstrated considerable potential in scientific domains such as drug repositioning. However, their effectiveness remains constrained when reasoning extends beyond the knowledge acquired during pretraining. Conventional approaches, such as fine-tuning or retrieval-augmented generation, face limitations in either imposing high computational overhead or failing to fully exploit structured scientific data. To overcome these challenges, we propose DrugMCTS, a novel framework that synergistically integrates RAG, multi-agent collaboration, and Monte Carlo Tree Search for drug repositioning. The framework employs five specialized agents tasked with retrieving and analyzing molecular and protein information, thereby enabling structured and iterative reasoning. Extensive experiments on the DrugBank and KIBA datasets demonstrate that DrugMCTS achieves substantially higher recall and robustness compared to both general-purpose LLMs and deep learning baselines. Our results highlight the importance of structured reasoning, agent-based collaboration, and feedback-driven search mechanisms in advancing LLM applications for drug repositioning.

Toxicity remains a leading cause of early-stage drug development failure. Despite advances in molecular design and property prediction, the task of molecular toxicity repair - generating structurally valid molecular alternatives with reduced toxicity - has not yet been systematically defined or benchmarked. To fill this gap, we introduce ToxiMol, the first benchmark task for general-purpose Multimodal Large Language Models (MLLMs) focused on molecular toxicity repair. We construct a standardized dataset covering 11 primary tasks and 560 representative toxic molecules spanning diverse mechanisms and granularities. We design a prompt annotation pipeline with mechanism-aware and task-adaptive capabilities, informed by expert toxicological knowledge. In parallel, we propose an automated evaluation framework, ToxiEval, which integrates toxicity endpoint prediction, synthetic accessibility, drug-likeness, and structural similarity into a high-throughput evaluation chain for repair success. We systematically assess nearly 30 mainstream general-purpose MLLMs and design multiple ablation studies to analyze key factors such as evaluation criteria, candidate diversity, and failure attribution. Experimental results show that although current MLLMs still face significant challenges on this task, they begin to demonstrate promising capabilities in toxicity understanding, semantic constraint adherence, and structure-aware molecule editing.

Foundation models applied to bio-molecular space hold promise to accelerate drug discovery. Molecular representation is key to building such models. Previous works have typically focused on a single representation or view of the molecules. Here, we develop a multi-view foundation model approach, that integrates molecular views of graph, image and text. Single-view foundation models are each pre-trained on a dataset of up to 200M molecules and then aggregated into combined representations. Our multi-view model is validated on a diverse set of 18 tasks, encompassing ligand-protein binding, molecular solubility, metabolism and toxicity. We show that the multi-view models perform robustly and are able to balance the strengths and weaknesses of specific views. We then apply this model to screen compounds against a large (>100 targets) set of G Protein-Coupled receptors (GPCRs). From this library of targets, we identify 33 that are related to Alzheimer's disease. On this subset, we employ our model to identify strong binders, which are validated through structure-based modeling and identification of key binding motifs.

Precision therapeutics require multimodal adaptive models that generate personalized treatment recommendations. We introduce TxAgent, an AI agent that leverages multi-step reasoning and real-time biomedical knowledge retrieval across a toolbox of 211 tools to analyze drug interactions, contraindications, and patient-specific treatment strategies. TxAgent evaluates how drugs interact at molecular, pharmacokinetic, and clinical levels, identifies contraindications based on patient comorbidities and concurrent medications, and tailors treatment strategies to individual patient characteristics. It retrieves and synthesizes evidence from multiple biomedical sources, assesses interactions between drugs and patient conditions, and refines treatment recommendations through iterative reasoning. It selects tools based on task objectives and executes structured function calls to solve therapeutic tasks that require clinical reasoning and cross-source validation. The ToolUniverse consolidates 211 tools from trusted sources, including all US FDA-approved drugs since 1939 and validated clinical insights from Open Targets. TxAgent outperforms leading LLMs, tool-use models, and reasoning agents across five new benchmarks: DrugPC, BrandPC, GenericPC, TreatmentPC, and DescriptionPC, covering 3,168 drug reasoning tasks and 456 personalized treatment scenarios. It achieves 92.1% accuracy in open-ended drug reasoning tasks, surpassing GPT-4o and outperforming DeepSeek-R1 (671B) in structured multi-step reasoning. TxAgent generalizes across drug name variants and descriptions. By integrating multi-step inference, real-time knowledge grounding, and tool-assisted decision-making, TxAgent ensures that treatment recommendations align with established clinical guidelines and real-world evidence, reducing the risk of adverse events and improving therapeutic decision-making.

Developing therapeutics is a lengthy and expensive process that requires the satisfaction of many different criteria, and AI models capable of expediting the process would be invaluable. However, the majority of current AI approaches address only a narrowly defined set of tasks, often circumscribed within a particular domain. To bridge this gap, we introduce Tx-LLM, a generalist large language model (LLM) fine-tuned from PaLM-2 which encodes knowledge about diverse therapeutic modalities. Tx-LLM is trained using a collection of 709 datasets that target 66 tasks spanning various stages of the drug discovery pipeline. Using a single set of weights, Tx-LLM simultaneously processes a wide variety of chemical or biological entities(small molecules, proteins, nucleic acids, cell lines, diseases) interleaved with free-text, allowing it to predict a broad range of associated properties, achieving competitive with state-of-the-art (SOTA) performance on 43 out of 66 tasks and exceeding SOTA on 22. Among these, Tx-LLM is particularly powerful and exceeds best-in-class performance on average for tasks combining molecular SMILES representations with text such as cell line names or disease names, likely due to context learned during pretraining. We observe evidence of positive transfer between tasks with diverse drug types (e.g.,tasks involving small molecules and tasks involving proteins), and we study the impact of model size, domain finetuning, and prompting strategies on performance. We believe Tx-LLM represents an important step towards LLMs encoding biochemical knowledge and could have a future role as an end-to-end tool across the drug discovery development pipeline.

Recently, pre-trained foundation models have enabled significant advancements in multiple fields. In molecular machine learning, however, where datasets are often hand-curated, and hence typically small, the lack of datasets with labeled features, and codebases to manage those datasets, has hindered the development of foundation models. In this work, we present seven novel datasets categorized by size into three distinct categories: ToyMix, LargeMix and UltraLarge. These datasets push the boundaries in both the scale and the diversity of supervised labels for molecular learning. They cover nearly 100 million molecules and over 3000 sparsely defined tasks, totaling more than 13 billion individual labels of both quantum and biological nature. In comparison, our datasets contain 300 times more data points than the widely used OGB-LSC PCQM4Mv2 dataset, and 13 times more than the quantum-only QM1B dataset. In addition, to support the development of foundational models based on our proposed datasets, we present the Graphium graph machine learning library which simplifies the process of building and training molecular machine learning models for multi-task and multi-level molecular datasets. Finally, we present a range of baseline results as a starting point of multi-task and multi-level training on these datasets. Empirically, we observe that performance on low-resource biological datasets show improvement by also training on large amounts of quantum data. This indicates that there may be potential in multi-task and multi-level training of a foundation model and fine-tuning it to resource-constrained downstream tasks.

Mamba, a State Space Model (SSM) that accelerates training by recasting recurrence as a parallel scan, has recently emerged as a linearly-scaling alternative to self-attention. Because of its unidirectional nature, each state in Mamba only has information of its previous states and is blind to states after. Current Mamba-based computer-vision methods typically overcome this by augmenting Mamba's global forward scan with a global backward scan, forming a bi-directional scan to restore a full receptive field. However, this operation doubles the computational load, eroding much of the efficiency advantage that originally Mamba have. To eliminate this extra scans, we introduce LBMamba, a locally bi-directional SSM block that embeds a lightweight locally backward scan inside the forward scan and executes it in per-thread registers. Building on LBMamba, we present LBVim, a backbone that alternates scan directions every two layers to recover a global receptive field without extra backward sweeps. We validate our approach on both natural images and whole slide images (WSIs) and show that it constantly offers a superior performance-throughput trade-off. Under the same throughput, LBVim achieves 0.8% to 1.6% higher top-1 accuracy on the ImageNet-1K classification dataset, 0.6% to 2.7% higher mIoU on the ADE20K semantic segmentation dataset, 0.9% higher APb and 1.1% higher APm on the COCO detection dataset. Our method also boosts the accuracy of four SOTA Mamba models, namely VMamba, LocalVim, PlainMamba and Adventurer, by 0.5% to 3.4%. We integrate LBMamba into the SOTA pathology multiple instance learning (MIL) model, MambaMIL, which is unidirectional. Experiments on 3 public WSI classification datasets show that our method achieves a relative improvement of up to 3.06% better AUC, 3.39% better F1, 1.67% better accuracy. Our code is available at https://github.com/cvlab-stonybrook/LBMamba.

Single-cell transcriptomics enabled the study of cellular heterogeneity in response to perturbations at the resolution of individual cells. However, scaling high-throughput screens (HTSs) to measure cellular responses for many drugs remains a challenge due to technical limitations and, more importantly, the cost of such multiplexed experiments. Thus, transferring information from routinely performed bulk RNA HTS is required to enrich single-cell data meaningfully. We introduce chemCPA, a new encoder-decoder architecture to study the perturbational effects of unseen drugs. We combine the model with an architecture surgery for transfer learning and demonstrate how training on existing bulk RNA HTS datasets can improve generalisation performance. Better generalisation reduces the need for extensive and costly screens at single-cell resolution. We envision that our proposed method will facilitate more efficient experiment designs through its ability to generate in-silico hypotheses, ultimately accelerating drug discovery.

Accurate prediction of Drug-Target Affinity (DTA) is of vital importance in early-stage drug discovery, facilitating the identification of drugs that can effectively interact with specific targets and regulate their activities. While wet experiments remain the most reliable method, they are time-consuming and resource-intensive, resulting in limited data availability that poses challenges for deep learning approaches. Existing methods have primarily focused on developing techniques based on the available DTA data, without adequately addressing the data scarcity issue. To overcome this challenge, we present the SSM-DTA framework, which incorporates three simple yet highly effective strategies: (1) A multi-task training approach that combines DTA prediction with masked language modeling (MLM) using paired drug-target data. (2) A semi-supervised training method that leverages large-scale unpaired molecules and proteins to enhance drug and target representations. This approach differs from previous methods that only employed molecules or proteins in pre-training. (3) The integration of a lightweight cross-attention module to improve the interaction between drugs and targets, further enhancing prediction accuracy. Through extensive experiments on benchmark datasets such as BindingDB, DAVIS, and KIBA, we demonstrate the superior performance of our framework. Additionally, we conduct case studies on specific drug-target binding activities, virtual screening experiments, drug feature visualizations, and real-world applications, all of which showcase the significant potential of our work. In conclusion, our proposed SSM-DTA framework addresses the data limitation challenge in DTA prediction and yields promising results, paving the way for more efficient and accurate drug discovery processes. Our code is available at https://github.com/QizhiPei/SSM-DTA{Github}.

Predicting multiple heterogeneous biological and medical targets is a challenge for traditional deep learning models. In contrast to single-task learning, in which a separate model is trained for each target, multi-task learning (MTL) optimizes a single model to predict multiple related targets simultaneously. To address this challenge, we propose the Multi-gate Mixture-of-Experts with Exclusivity (MMoEEx). Our work aims to tackle the heterogeneous MTL setting, in which the same model optimizes multiple tasks with different characteristics. Such a scenario can overwhelm current MTL approaches due to the challenges in balancing shared and task-specific representations and the need to optimize tasks with competing optimization paths. Our method makes two key contributions: first, we introduce an approach to induce more diversity among experts, thus creating representations more suitable for highly imbalanced and heterogenous MTL learning; second, we adopt a two-step optimization [6, 11] approach to balancing the tasks at the gradient level. We validate our method on three MTL benchmark datasets, including Medical Information Mart for Intensive Care (MIMIC-III) and PubChem BioAssay (PCBA).

Micro-expression recognition (MER), a critical subfield of affective computing, presents greater challenges than macro-expression recognition due to its brief duration and low intensity. While incorporating prior knowledge has been shown to enhance MER performance, existing methods predominantly rely on simplistic, singular sources of prior knowledge, failing to fully exploit multi-source information. This paper introduces the Multi-Prior Fusion Network (MPFNet), leveraging a progressive training strategy to optimize MER tasks. We propose two complementary encoders: the Generic Feature Encoder (GFE) and the Advanced Feature Encoder (AFE), both based on Inflated 3D ConvNets (I3D) with Coordinate Attention (CA) mechanisms, to improve the model's ability to capture spatiotemporal and channel-specific features. Inspired by developmental psychology, we present two variants of MPFNet--MPFNet-P and MPFNet-C--corresponding to two fundamental modes of infant cognitive development: parallel and hierarchical processing. These variants enable the evaluation of different strategies for integrating prior knowledge. Extensive experiments demonstrate that MPFNet significantly improves MER accuracy while maintaining balanced performance across categories, achieving accuracies of 0.811, 0.924, and 0.857 on the SMIC, CASME II, and SAMM datasets, respectively. To the best of our knowledge, our approach achieves state-of-the-art performance on the SMIC and SAMM datasets.

Despite substantial progress in video understanding, most existing datasets are limited to Earth's gravitational conditions. However, microgravity alters human motion, interactions, and visual semantics, revealing a critical gap for real-world vision systems. This presents a challenge for domain-robust video understanding in safety-critical space applications. To address this, we introduce MicroG-4M, the first benchmark for spatio-temporal and semantic understanding of human activities in microgravity. Constructed from real-world space missions and cinematic simulations, the dataset includes 4,759 clips covering 50 actions, 1,238 context-rich captions, and over 7,000 question-answer pairs on astronaut activities and scene understanding. MicroG-4M supports three core tasks: fine-grained multi-label action recognition, temporal video captioning, and visual question answering, enabling a comprehensive evaluation of both spatial localization and semantic reasoning in microgravity contexts. We establish baselines using state-of-the-art models. All data, annotations, and code are available at https://github.com/LEI-QI-233/HAR-in-Space.

This paper introduces M^{3}-20M, a large-scale Multi-Modal Molecular dataset that contains over 20 million molecules. Designed to support AI-driven drug design and discovery, M^{3}-20M is 71 times more in the number of molecules than the largest existing dataset, providing an unprecedented scale that can highly benefit training or fine-tuning large (language) models with superior performance for drug design and discovery. This dataset integrates one-dimensional SMILES, two-dimensional molecular graphs, three-dimensional molecular structures, physicochemical properties, and textual descriptions collected through web crawling and generated by using GPT-3.5, offering a comprehensive view of each molecule. To demonstrate the power of M^{3}-20M in drug design and discovery, we conduct extensive experiments on two key tasks: molecule generation and molecular property prediction, using large language models including GLM4, GPT-3.5, and GPT-4. Our experimental results show that M^{3}-20M can significantly boost model performance in both tasks. Specifically, it enables the models to generate more diverse and valid molecular structures and achieve higher property prediction accuracy than the existing single-modal datasets, which validates the value and potential of M^{3}-20M in supporting AI-driven drug design and discovery. The dataset is available at https://github.com/bz99bz/M-3.

We present an elegant and effective approach for addressing limitations in existing multi-label classification models by incorporating interaction matching, a concept shown to be useful for ad-hoc search result ranking. By performing soft n-gram interaction matching, we match labels with natural language descriptions (which are common to have in most multi-labeling tasks). Our approach can be used to enhance existing multi-label classification approaches, which are biased toward frequently-occurring labels. We evaluate our approach on two challenging tasks: automatic medical coding of clinical notes and automatic labeling of entities from software tutorial text. Our results show that our method can yield up to an 11% relative improvement in macro performance, with most of the gains stemming labels that appear infrequently in the training set (i.e., the long tail of labels).

We resolve difficulties in training and sampling from a discrete generative model by learning a smoothed energy function, sampling from the smoothed data manifold with Langevin Markov chain Monte Carlo (MCMC), and projecting back to the true data manifold with one-step denoising. Our Discrete Walk-Jump Sampling formalism combines the contrastive divergence training of an energy-based model and improved sample quality of a score-based model, while simplifying training and sampling by requiring only a single noise level. We evaluate the robustness of our approach on generative modeling of antibody proteins and introduce the distributional conformity score to benchmark protein generative models. By optimizing and sampling from our models for the proposed distributional conformity score, 97-100% of generated samples are successfully expressed and purified and 70% of functional designs show equal or improved binding affinity compared to known functional antibodies on the first attempt in a single round of laboratory experiments. We also report the first demonstration of long-run fast-mixing MCMC chains where diverse antibody protein classes are visited in a single MCMC chain.

Structure-Based Drug Design (SBDD) is a powerful strategy in computational drug discovery, utilizing three-dimensional protein structures to guide the design of molecules with improved binding affinity. However, capturing complex protein-ligand interactions across multiple scales remains challenging, as current methods often overlook the hierarchical organization and intrinsic asymmetry of these interactions. To address these limitations, we propose MSCoD, a novel Bayesian updating-based generative framework for structure-based drug design. In our MSCoD, Multi-Scale Information Bottleneck (MSIB) was developed, which enables semantic compression at multiple abstraction levels for efficient hierarchical feature extraction. Furthermore, a multi-head cooperative attention (MHCA) mechanism was developed, which employs asymmetric protein-to-ligand attention to capture diverse interaction types while addressing the dimensionality disparity between proteins and ligands. Empirical studies showed that MSCoD outperforms state-of-the-art methods on the benchmark dataset. Case studies on challenging targets such as KRAS G12D further demonstrate its applicability in real-world scenarios. The code and data underlying this article are freely available at https://github.com/xulong0826/MSCoD.

In the era of Large Language Models (LLMs), given their remarkable text understanding and generation abilities, there is an unprecedented opportunity to develop new, LLM-based methods for trustworthy medical knowledge synthesis, extraction and summarization. This paper focuses on the problem of Pharmacovigilance (PhV), where the significance and challenges lie in identifying Adverse Drug Events (ADEs) from diverse text sources, such as medical literature, clinical notes, and drug labels. Unfortunately, this task is hindered by factors including variations in the terminologies of drugs and outcomes, and ADE descriptions often being buried in large amounts of narrative text. We present MALADE, the first effective collaborative multi-agent system powered by LLM with Retrieval Augmented Generation for ADE extraction from drug label data. This technique involves augmenting a query to an LLM with relevant information extracted from text resources, and instructing the LLM to compose a response consistent with the augmented data. MALADE is a general LLM-agnostic architecture, and its unique capabilities are: (1) leveraging a variety of external sources, such as medical literature, drug labels, and FDA tools (e.g., OpenFDA drug information API), (2) extracting drug-outcome association in a structured format along with the strength of the association, and (3) providing explanations for established associations. Instantiated with GPT-4 Turbo or GPT-4o, and FDA drug label data, MALADE demonstrates its efficacy with an Area Under ROC Curve of 0.90 against the OMOP Ground Truth table of ADEs. Our implementation leverages the Langroid multi-agent LLM framework and can be found at https://github.com/jihyechoi77/malade.

Automated drug discovery offers significant potential for accelerating the development of novel therapeutics by substituting labor-intensive human workflows with machine-driven processes. However, molecules generated by artificial intelligence may unintentionally infringe on existing patents, posing legal and financial risks that impede the full automation of drug discovery pipelines. This paper introduces PatentFinder, a novel multi-agent and tool-enhanced intelligence system that can accurately and comprehensively evaluate small molecules for patent infringement. PatentFinder features five specialized agents that collaboratively analyze patent claims and molecular structures with heuristic and model-based tools, generating interpretable infringement reports. To support systematic evaluation, we curate MolPatent-240, a benchmark dataset tailored for patent infringement assessment algorithms. On this benchmark, PatentFinder outperforms baseline methods that rely solely on large language models or specialized chemical tools, achieving a 13.8% improvement in F1-score and a 12% increase in accuracy. Additionally, PatentFinder autonomously generates detailed and interpretable patent infringement reports, showcasing enhanced accuracy and improved interpretability. The high accuracy and interpretability of PatentFinder make it a valuable and reliable tool for automating patent infringement assessments, offering a practical solution for integrating patent protection analysis into the drug discovery pipeline.

Recent advances in machine learning have made significant contributions to drug discovery. Deep neural networks in particular have been demonstrated to provide significant boosts in predictive power when inferring the properties and activities of small-molecule compounds. However, the applicability of these techniques has been limited by the requirement for large amounts of training data. In this work, we demonstrate how one-shot learning can be used to significantly lower the amounts of data required to make meaningful predictions in drug discovery applications. We introduce a new architecture, the residual LSTM embedding, that, when combined with graph convolutional neural networks, significantly improves the ability to learn meaningful distance metrics over small-molecules. We open source all models introduced in this work as part of DeepChem, an open-source framework for deep-learning in drug discovery.

Drug-protein binding and dissociation dynamics are fundamental to understanding molecular interactions in biological systems. While many tools for drug-protein interaction studies have emerged, especially artificial intelligence (AI)-based generative models, predictive tools on binding/dissociation kinetics and dynamics are still limited. We propose a novel research paradigm that combines molecular dynamics (MD) simulations, enhanced sampling, and AI generative models to address this issue. We propose an enhanced sampling strategy to efficiently implement the drug-protein dissociation process in MD simulations and estimate the free energy surface (FES). We constructed a program pipeline of MD simulations based on this sampling strategy, thus generating a dataset including 26,612 drug-protein dissociation trajectories containing about 13 million frames. We named this dissociation dynamics dataset DD-13M and used it to train a deep equivariant generative model UnbindingFlow, which can generate collision-free dissociation trajectories. The DD-13M database and UnbindingFlow model represent a significant advancement in computational structural biology, and we anticipate its broad applicability in machine learning studies of drug-protein interactions. Our ongoing efforts focus on expanding this methodology to encompass a broader spectrum of drug-protein complexes and exploring novel applications in pathway prediction.

The challenge of replicating research results has posed a significant impediment to the field of molecular biology. The advent of modern intelligent systems has led to notable progress in various domains. Consequently, we embarked on an investigation of intelligent monitoring systems as a means of tackling the issue of the reproducibility crisis. Specifically, we first curate a comprehensive multimodal dataset, named ProBio, as an initial step towards this objective. This dataset comprises fine-grained hierarchical annotations intended for the purpose of studying activity understanding in BioLab. Next, we devise two challenging benchmarks, transparent solution tracking and multimodal action recognition, to emphasize the unique characteristics and difficulties associated with activity understanding in BioLab settings. Finally, we provide a thorough experimental evaluation of contemporary video understanding models and highlight their limitations in this specialized domain to identify potential avenues for future research. We hope ProBio with associated benchmarks may garner increased focus on modern AI techniques in the realm of molecular biology.

Due to the expensive costs of collecting labels in multi-label classification datasets, partially annotated multi-label classification has become an emerging field in computer vision. One baseline approach to this task is to assume unobserved labels as negative labels, but this assumption induces label noise as a form of false negative. To understand the negative impact caused by false negative labels, we study how these labels affect the model's explanation. We observe that the explanation of two models, trained with full and partial labels each, highlights similar regions but with different scaling, where the latter tends to have lower attribution scores. Based on these findings, we propose to boost the attribution scores of the model trained with partial labels to make its explanation resemble that of the model trained with full labels. Even with the conceptually simple approach, the multi-label classification performance improves by a large margin in three different datasets on a single positive label setting and one on a large-scale partial label setting. Code is available at https://github.com/youngwk/BridgeGapExplanationPAMC.

Traditional drug design faces significant challenges due to inherent chemical and biological complexities, often resulting in high failure rates in clinical trials. Deep learning advancements, particularly generative models, offer potential solutions to these challenges. One promising algorithm is DrugGPT, a transformer-based model, that generates small molecules for input protein sequences. Although promising, it generates both chemically valid and invalid structures and does not incorporate the features of approved drugs, resulting in time-consuming and inefficient drug discovery. To address these issues, we introduce DrugGen, an enhanced model based on the DrugGPT structure. DrugGen is fine-tuned on approved drug-target interactions and optimized with proximal policy optimization. By giving reward feedback from protein-ligand binding affinity prediction using pre-trained transformers (PLAPT) and a customized invalid structure assessor, DrugGen significantly improves performance. Evaluation across multiple targets demonstrated that DrugGen achieves 100% valid structure generation compared to 95.5% with DrugGPT and produced molecules with higher predicted binding affinities (7.22 [6.30-8.07]) compared to DrugGPT (5.81 [4.97-6.63]) while maintaining diversity and novelty. Docking simulations further validate its ability to generate molecules targeting binding sites effectively. For example, in the case of fatty acid-binding protein 5 (FABP5), DrugGen generated molecules with superior docking scores (FABP5/11, -9.537 and FABP5/5, -8.399) compared to the reference molecule (Palmitic acid, -6.177). Beyond lead compound generation, DrugGen also shows potential for drug repositioning and creating novel pharmacophores for existing targets. By producing high-quality small molecules, DrugGen provides a high-performance medium for advancing pharmaceutical research and drug discovery.

Understanding and designing biomolecules, such as proteins and small molecules, is central to advancing drug discovery, synthetic biology, and enzyme engineering. Recent breakthroughs in Artificial Intelligence (AI) have revolutionized biomolecular research, achieving remarkable accuracy in biomolecular prediction and design. However, a critical gap remains between AI's computational power and researchers' intuition, using natural language to align molecular complexity with human intentions. Large Language Models (LLMs) have shown potential to interpret human intentions, yet their application to biomolecular research remains nascent due to challenges including specialized knowledge requirements, multimodal data integration, and semantic alignment between natural language and biomolecules. To address these limitations, we present InstructBioMol, a novel LLM designed to bridge natural language and biomolecules through a comprehensive any-to-any alignment of natural language, molecules, and proteins. This model can integrate multimodal biomolecules as input, and enable researchers to articulate design goals in natural language, providing biomolecular outputs that meet precise biological needs. Experimental results demonstrate InstructBioMol can understand and design biomolecules following human instructions. Notably, it can generate drug molecules with a 10% improvement in binding affinity and design enzymes that achieve an ESP Score of 70.4, making it the only method to surpass the enzyme-substrate interaction threshold of 60.0 recommended by the ESP developer. This highlights its potential to transform real-world biomolecular research.

Identifying drug-target interactions is essential for developing effective therapeutics. Binding affinity quantifies these interactions, and traditional approaches rely on computationally intensive 3D structural data. In contrast, language models can efficiently process sequential data, offering an alternative approach to molecular representation. In the current study, we introduce BAPULM, an innovative sequence-based framework that leverages the chemical latent representations of proteins via ProtT5-XL-U50 and ligands through MolFormer, eliminating reliance on complex 3D configurations. Our approach was validated extensively on benchmark datasets, achieving scoring power (R) values of 0.925 pm 0.043, 0.914 pm 0.004, and 0.8132 pm 0.001 on benchmark1k2101, Test2016_290, and CSAR-HiQ_36, respectively. These findings indicate the robustness and accuracy of BAPULM across diverse datasets and underscore the potential of sequence-based models in-silico drug discovery, offering a scalable alternative to 3D-centric methods for screening potential ligands.

High-throughput drug screening -- using cell imaging or gene expression measurements as readouts of drug effect -- is a critical tool in biotechnology to assess and understand the relationship between the chemical structure and biological activity of a drug. Since large-scale screens have to be divided into multiple experiments, a key difficulty is dealing with batch effects, which can introduce systematic errors and non-biological associations in the data. We propose InfoCORE, an Information maximization approach for COnfounder REmoval, to effectively deal with batch effects and obtain refined molecular representations. InfoCORE establishes a variational lower bound on the conditional mutual information of the latent representations given a batch identifier. It adaptively reweighs samples to equalize their implied batch distribution. Extensive experiments on drug screening data reveal InfoCORE's superior performance in a multitude of tasks including molecular property prediction and molecule-phenotype retrieval. Additionally, we show results for how InfoCORE offers a versatile framework and resolves general distribution shifts and issues of data fairness by minimizing correlation with spurious features or removing sensitive attributes. The code is available at https://github.com/uhlerlab/InfoCORE.

In multi-label classification, each example in a dataset may be annotated as belonging to one or more classes (or none of the classes). Example applications include image (or document) tagging where each possible tag either applies to a particular image (or document) or not. With many possible classes to consider, data annotators are likely to make errors when labeling such data in practice. Here we consider algorithms for finding mislabeled examples in multi-label classification datasets. We propose an extension of the Confident Learning framework to this setting, as well as a label quality score that ranks examples with label errors much higher than those which are correctly labeled. Both approaches can utilize any trained classifier. After demonstrating that our methodology empirically outperforms other algorithms for label error detection, we apply our approach to discover many label errors in the CelebA image tagging dataset.

Micro-expressions are typically regarded as unconscious manifestations of a person's genuine emotions. However, their short duration and subtle signals pose significant challenges for downstream recognition. We propose a multi-task learning framework named the Adaptive Motion Magnification and Sparse Mamba (AMMSM) to address this. This framework aims to enhance the accurate capture of micro-expressions through self-supervised subtle motion magnification, while the sparse spatial selection Mamba architecture combines sparse activation with the advanced Visual Mamba model to model key motion regions and their valuable representations more effectively. Additionally, we employ evolutionary search to optimize the magnification factor and the sparsity ratios of spatial selection, followed by fine-tuning to improve performance further. Extensive experiments on two standard datasets demonstrate that the proposed AMMSM achieves state-of-the-art (SOTA) accuracy and robustness.

A generalist robotic policy needs both semantic understanding for task planning and the ability to interact with the environment through predictive capabilities. To tackle this, we present MM-ACT, a unified Vision-Language-Action (VLA) model that integrates text, image, and action in shared token space and performs generation across all three modalities. MM-ACT adopts a re-mask parallel decoding strategy for text and image generation, and employs a one-step parallel decoding strategy for action generation to improve efficiency. We introduce Context-Shared Multimodal Learning, a unified training paradigm that supervises generation in all three modalities from a shared context, enhancing action generation through cross-modal learning. Experiments were conducted on the LIBERO simulation and Franka real-robot setups as well as RoboTwin2.0 to assess in-domain and out-of-domain performances respectively. Our approach achieves a success rate of 96.3% on LIBERO, 72.0% across three tasks of real Franka, and 52.38% across eight bimanual tasks of RoboTwin2.0 with an additional gain of 9.25% from cross-modal learning. We release our codes, models and data at https://github.com/HHYHRHY/MM-ACT.

Discovering novel drug candidate molecules is one of the most fundamental and critical steps in drug development. Generative deep learning models, which create synthetic data given a probability distribution, offer a high potential for designing de novo molecules. However, to be utilisable in real life drug development pipelines, these models should be able to design drug like and target centric molecules. In this study, we propose an end to end generative system, DrugGEN, for the de novo design of drug candidate molecules that interact with intended target proteins. The proposed method represents molecules as graphs and processes them via a generative adversarial network comprising graph transformer layers. The system is trained using a large dataset of drug like compounds and target specific bioactive molecules to design effective inhibitory molecules against the AKT1 protein, which is critically important in developing treatments for various types of cancer. We conducted molecular docking and dynamics to assess the target centric generation performance of the model, as well as attention score visualisation to examine model interpretability. In parallel, selected compounds were chemically synthesised and evaluated in the context of in vitro enzymatic assays, which identified two bioactive molecules that inhibited AKT1 at low micromolar concentrations. These results indicate that DrugGEN's de novo molecules have a high potential for interacting with the AKT1 protein at the level of its native ligands. Using the open access DrugGEN codebase, it is possible to easily train models for other druggable proteins, given a dataset of experimentally known bioactive molecules.

Peptide therapeutics, a major class of medicines, have achieved remarkable success across diseases such as diabetes and cancer, with landmark examples such as GLP-1 receptor agonists revolutionizing the treatment of type-2 diabetes and obesity. Despite their success, designing peptides that satisfy multiple conflicting objectives, such as target binding affinity, solubility, and membrane permeability, remains a major challenge. Classical drug development and structure-based design are ineffective for such tasks, as they fail to optimize global functional properties critical for therapeutic efficacy. Existing generative frameworks are largely limited to continuous spaces, unconditioned outputs, or single-objective guidance, making them unsuitable for discrete sequence optimization across multiple properties. To address this, we present PepTune, a multi-objective discrete diffusion model for the simultaneous generation and optimization of therapeutic peptide SMILES. Built on the Masked Discrete Language Model (MDLM) framework, PepTune ensures valid peptide structures with state-dependent masking schedules and penalty-based objectives. To guide the diffusion process, we propose a Monte Carlo Tree Search (MCTS)-based strategy that balances exploration and exploitation to iteratively refine Pareto-optimal sequences. MCTS integrates classifier-based rewards with search-tree expansion, overcoming gradient estimation challenges and data sparsity inherent to discrete spaces. Using PepTune, we generate diverse, chemically-modified peptides optimized for multiple therapeutic properties, including target binding affinity, membrane permeability, solubility, hemolysis, and non-fouling characteristics on various disease-relevant targets. In total, our results demonstrate that MCTS-guided discrete diffusion is a powerful and modular approach for multi-objective sequence design in discrete state spaces.

With the development of computer-assisted techniques, research communities including biochemistry and deep learning have been devoted into the drug discovery field for over a decade. Various applications of deep learning have drawn great attention in drug discovery, such as molecule generation, molecular property prediction, retrosynthesis prediction, and reaction prediction. While most existing surveys only focus on one of the applications, limiting the view of researchers in the community. In this paper, we present a comprehensive review on the aforementioned four aspects, and discuss the relationships among different applications. The latest literature and classical benchmarks are presented for better understanding the development of variety of approaches. We commence by summarizing the molecule representation format in these works, followed by an introduction of recent proposed approaches for each of the four tasks. Furthermore, we review a variety of commonly used datasets and evaluation metrics and compare the performance of deep learning-based models. Finally, we conclude by identifying remaining challenges and discussing the future trend for deep learning methods in drug discovery.

In line with recent advances in neural drug design and sensitivity prediction, we propose a novel architecture for interpretable prediction of anticancer compound sensitivity using a multimodal attention-based convolutional encoder. Our model is based on the three key pillars of drug sensitivity: compounds' structure in the form of a SMILES sequence, gene expression profiles of tumors and prior knowledge on intracellular interactions from protein-protein interaction networks. We demonstrate that our multiscale convolutional attention-based (MCA) encoder significantly outperforms a baseline model trained on Morgan fingerprints, a selection of encoders based on SMILES as well as previously reported state of the art for multimodal drug sensitivity prediction (R2 = 0.86 and RMSE = 0.89). Moreover, the explainability of our approach is demonstrated by a thorough analysis of the attention weights. We show that the attended genes significantly enrich apoptotic processes and that the drug attention is strongly correlated with a standard chemical structure similarity index. Finally, we report a case study of two receptor tyrosine kinase (RTK) inhibitors acting on a leukemia cell line, showcasing the ability of the model to focus on informative genes and submolecular regions of the two compounds. The demonstrated generalizability and the interpretability of our model testify its potential for in-silico prediction of anticancer compound efficacy on unseen cancer cells, positioning it as a valid solution for the development of personalized therapies as well as for the evaluation of candidate compounds in de novo drug design.

Example synthesis is one of the leading methods to tackle the problem of few-shot learning, where only a small number of samples per class are available. However, current synthesis approaches only address the scenario of a single category label per image. In this work, we propose a novel technique for synthesizing samples with multiple labels for the (yet unhandled) multi-label few-shot classification scenario. We propose to combine pairs of given examples in feature space, so that the resulting synthesized feature vectors will correspond to examples whose label sets are obtained through certain set operations on the label sets of the corresponding input pairs. Thus, our method is capable of producing a sample containing the intersection, union or set-difference of labels present in two input samples. As we show, these set operations generalize to labels unseen during training. This enables performing augmentation on examples of novel categories, thus, facilitating multi-label few-shot classifier learning. We conduct numerous experiments showing promising results for the label-set manipulation capabilities of the proposed approach, both directly (using the classification and retrieval metrics), and in the context of performing data augmentation for multi-label few-shot learning. We propose a benchmark for this new and challenging task and show that our method compares favorably to all the common baselines.

The drug development pipeline for a new compound can last 10-20 years and cost over 10 billion. Drug repurposing offers a more time- and cost-effective alternative. Computational approaches based on biomedical knowledge graph representations have recently yielded new drug repurposing hypotheses. In this study, we present a novel, disease-specific hypergraph representation learning technique to derive contextual embeddings of biological pathways of various lengths but that all start at any given drug and all end at the disease of interest. Further, we extend this method to multi-disease hypergraphs. To determine the repurposing potential of each of the 1,522 drugs, we derive drug-specific distributions of cosine similarity values and ultimately consider the median for ranking. Cosine similarity values are computed between (1) all biological pathways starting at the considered drug and ending at the disease of interest and (2) all biological pathways starting at drugs currently prescribed against that disease and ending at the disease of interest. We illustrate our approach with Alzheimer's disease (AD) and two of its risk factors: hypertension (HTN) and type 2 diabetes (T2D). We compare each drug's rank across four hypergraph settings (single- or multi-disease): AD only, AD + HTN, AD + T2D, and AD + HTN + T2D. Notably, our framework led to the identification of two promising drugs whose repurposing potential was significantly higher in hypergraphs combining two diseases: dapagliflozin (antidiabetic; moved up, from top 32% to top 7%, across all considered drugs) and debrisoquine (antihypertensive; moved up, from top 76% to top 23%). Our approach serves as a hypothesis generation tool, to be paired with a validation pipeline relying on laboratory experiments and semi-automated parsing of the biomedical literature.

This paper presents a multi-label topic model for financial texts like ad-hoc announcements, 8-K filings, finance related news or annual reports. I train the model on a new financial multi-label database consisting of 3,044 German ad-hoc announcements that are labeled manually using 20 predefined, economically motivated topics. The best model achieves a macro F1 score of more than 85%. Translating the data results in an English version of the model with similar performance. As application of the model, I investigate differences in stock market reactions across topics. I find evidence for strong positive or negative market reactions for some topics, like announcements of new Large Scale Projects or Bankruptcy Filings, while I do not observe significant price effects for some other topics. Furthermore, in contrast to previous studies, the multi-label structure of the model allows to analyze the effects of co-occurring topics on stock market reactions. For many cases, the reaction to a specific topic depends heavily on the co-occurrence with other topics. For example, if allocated capital from a Seasoned Equity Offering (SEO) is used for restructuring a company in the course of a Bankruptcy Proceeding, the market reacts positively on average. However, if that capital is used for covering unexpected, additional costs from the development of new drugs, the SEO implies negative reactions on average.

Scientific research demands sophisticated reasoning over multimodal data, a challenge especially prevalent in biology. Despite recent advances in multimodal large language models (MLLMs) for AI-assisted research, existing multimodal reasoning benchmarks only target up to college-level difficulty, while research-level benchmarks emphasize lower-level perception, falling short of the complex multimodal reasoning needed for scientific discovery. To bridge this gap, we introduce MicroVQA, a visual-question answering (VQA) benchmark designed to assess three reasoning capabilities vital in research workflows: expert image understanding, hypothesis generation, and experiment proposal. MicroVQA consists of 1,042 multiple-choice questions (MCQs) curated by biology experts across diverse microscopy modalities, ensuring VQA samples represent real scientific practice. In constructing the benchmark, we find that standard MCQ generation methods induce language shortcuts, motivating a new two-stage pipeline: an optimized LLM prompt structures question-answer pairs into MCQs; then, an agent-based `RefineBot' updates them to remove shortcuts. Benchmarking on state-of-the-art MLLMs reveal a peak performance of 53\%; models with smaller LLMs only slightly underperform top models, suggesting that language-based reasoning is less challenging than multimodal reasoning; and tuning with scientific articles enhances performance. Expert analysis of chain-of-thought responses shows that perception errors are the most frequent, followed by knowledge errors and then overgeneralization errors. These insights highlight the challenges in multimodal scientific reasoning, showing MicroVQA is a valuable resource advancing AI-driven biomedical research. MicroVQA is available at https://huggingface.co/datasets/jmhb/microvqa, and project page at https://jmhb0.github.io/microvqa.

In the development of science, accurate and reproducible documentation of the experimental process is crucial. Automatic recognition of the actions in experiments from videos would help experimenters by complementing the recording of experiments. Towards this goal, we propose FineBio, a new fine-grained video dataset of people performing biological experiments. The dataset consists of multi-view videos of 32 participants performing mock biological experiments with a total duration of 14.5 hours. One experiment forms a hierarchical structure, where a protocol consists of several steps, each further decomposed into a set of atomic operations. The uniqueness of biological experiments is that while they require strict adherence to steps described in each protocol, there is freedom in the order of atomic operations. We provide hierarchical annotation on protocols, steps, atomic operations, object locations, and their manipulation states, providing new challenges for structured activity understanding and hand-object interaction recognition. To find out challenges on activity understanding in biological experiments, we introduce baseline models and results on four different tasks, including (i) step segmentation, (ii) atomic operation detection (iii) object detection, and (iv) manipulated/affected object detection. Dataset and code are available from https://github.com/aistairc/FineBio.

The global cost of drug discovery and development exceeds $200 billion annually. The main results of drug discovery and development are the outcomes of clinical trials, which directly influence the regulatory approval of new drug candidates and ultimately affect patient outcomes. Despite their significance, large-scale, high-quality clinical trial outcome data are not readily available to the public. Suppose a large clinical trial outcome dataset is provided; machine learning researchers can potentially develop accurate prediction models using past trials and outcome labels, which could help prioritize and optimize therapeutic programs, ultimately benefiting patients. This paper introduces Clinical Trial Outcome (CTO) dataset, the largest trial outcome dataset with around 479K clinical trials, aggregating outcomes from multiple sources of weakly supervised labels, minimizing the noise from individual sources, and eliminating the need for human annotation. These sources include large language model (LLM) decisions on trial-related documents, news headline sentiments, stock prices of trial sponsors, trial linkages across phases, and other signals such as patient dropout rates and adverse events. CTO's labels show unprecedented agreement with supervised clinical trial outcome labels from test split of the supervised TOP dataset, with a 91 F1.

The approval success rate of drug candidates is very low with the majority of failure due to safety and efficacy. Increasingly available high dimensional information on targets, drug molecules and indications provides an opportunity for ML methods to integrate multiple data modalities and better predict clinically promising drug targets. Notably, drug targets with human genetics evidence are shown to have better odds to succeed. However, a recent tensor factorization-based approach found that additional information on targets and indications might not necessarily improve the predictive accuracy. Here we revisit this approach by integrating different types of human genetics evidence collated from publicly available sources to support each target-indication pair. We use Bayesian tensor factorization to show that models incorporating all available human genetics evidence (rare disease, gene burden, common disease) modestly improves the clinical outcome prediction over models using single line of genetics evidence. We provide additional insight into the relative predictive power of different types of human genetics evidence for predicting the success of clinical outcomes.

Therapeutic development is a costly and high-risk endeavor that is often plagued by high failure rates. To address this, we introduce TxGemma, a suite of efficient, generalist large language models (LLMs) capable of therapeutic property prediction as well as interactive reasoning and explainability. Unlike task-specific models, TxGemma synthesizes information from diverse sources, enabling broad application across the therapeutic development pipeline. The suite includes 2B, 9B, and 27B parameter models, fine-tuned from Gemma-2 on a comprehensive dataset of small molecules, proteins, nucleic acids, diseases, and cell lines. Across 66 therapeutic development tasks, TxGemma achieved superior or comparable performance to the state-of-the-art generalist model on 64 (superior on 45), and against state-of-the-art specialist models on 50 (superior on 26). Fine-tuning TxGemma models on therapeutic downstream tasks, such as clinical trial adverse event prediction, requires less training data than fine-tuning base LLMs, making TxGemma suitable for data-limited applications. Beyond these predictive capabilities, TxGemma features conversational models that bridge the gap between general LLMs and specialized property predictors. These allow scientists to interact in natural language, provide mechanistic reasoning for predictions based on molecular structure, and engage in scientific discussions. Building on this, we further introduce Agentic-Tx, a generalist therapeutic agentic system powered by Gemini 2.5 that reasons, acts, manages diverse workflows, and acquires external domain knowledge. Agentic-Tx surpasses prior leading models on the Humanity's Last Exam benchmark (Chemistry & Biology) with 52.3% relative improvement over o3-mini (high) and 26.7% over o3-mini (high) on GPQA (Chemistry) and excels with improvements of 6.3% (ChemBench-Preference) and 2.4% (ChemBench-Mini) over o3-mini (high).

Drug toxicity remains a major challenge in pharmaceutical development. Recent machine learning models have improved in silico toxicity prediction, but their reliance on annotated data and lack of interpretability limit their applicability. This limits their ability to capture organ-specific toxicities driven by complex biological mechanisms. Large language models (LLMs) offer a promising alternative through step-by-step reasoning and integration of textual data, yet prior approaches lack biological context and transparent rationale. To address this issue, we propose CoTox, a novel framework that integrates LLM with chain-of-thought (CoT) reasoning for multi-toxicity prediction. CoTox combines chemical structure data, biological pathways, and gene ontology (GO) terms to generate interpretable toxicity predictions through step-by-step reasoning. Using GPT-4o, we show that CoTox outperforms both traditional machine learning and deep learning model. We further examine its performance across various LLMs to identify where CoTox is most effective. Additionally, we find that representing chemical structures with IUPAC names, which are easier for LLMs to understand than SMILES, enhances the model's reasoning ability and improves predictive performance. To demonstrate its practical utility in drug development, we simulate the treatment of relevant cell types with drug and incorporated the resulting biological context into the CoTox framework. This approach allow CoTox to generate toxicity predictions aligned with physiological responses, as shown in case study. This result highlights the potential of LLM-based frameworks to improve interpretability and support early-stage drug safety assessment. The code and prompt used in this work are available at https://github.com/dmis-lab/CoTox.

Activity and property prediction models are the central workhorses in drug discovery and materials sciences, but currently they have to be trained or fine-tuned for new tasks. Without training or fine-tuning, scientific language models could be used for such low-data tasks through their announced zero- and few-shot capabilities. However, their predictive quality at activity prediction is lacking. In this work, we envision a novel type of activity prediction model that is able to adapt to new prediction tasks at inference time, via understanding textual information describing the task. To this end, we propose a new architecture with separate modules for chemical and natural language inputs, and a contrastive pre-training objective on data from large biochemical databases. In extensive experiments, we show that our method CLAMP yields improved predictive performance on few-shot learning benchmarks and zero-shot problems in drug discovery. We attribute the advances of our method to the modularized architecture and to our pre-training objective.

Structural biology relies on accurate three-dimensional biomolecular structures to advance our understanding of biological functions, disease mechanisms, and therapeutics. While recent advances in deep learning have enabled the development of all-atom foundation models for molecular modeling and generation, existing approaches face challenges in generalization due to the multi-modal nature of atomic data and the lack of comprehensive analysis of training and sampling strategies. To address these limitations, we propose PharMolixFM, a unified framework for constructing all-atom foundation models based on multi-modal generative techniques. Our framework includes three variants using state-of-the-art multi-modal generative models. By formulating molecular tasks as a generalized denoising process with task-specific priors, PharMolixFM achieves robust performance across various structural biology applications. Experimental results demonstrate that PharMolixFM-Diff achieves competitive prediction accuracy in protein-small-molecule docking (83.9% vs. 90.2% RMSD < 2Å, given pocket) with significantly improved inference speed. Moreover, we explore the empirical inference scaling law by introducing more sampling repeats or steps. Our code and model are available at https://github.com/PharMolix/OpenBioMed.

The assumption that response and predictor belong to the same statistical unit may be violated in practice. Unbiased estimation and recovery of true label ordering based on unlabeled data are challenging tasks and have attracted increasing attentions in the recent literature. In this paper, we present a relatively complete analysis of label permutation problem for the generalized linear model with multivariate responses. The theory is established under different scenarios, with knowledge of true parameters, with partial knowledge of underlying label permutation matrix and without any knowledge. Our results remove the stringent conditions required by the current literature and are further extended to the missing observation setting which has never been considered in the field of label permutation problem. On computational side, we propose two methods, "maximum likelihood estimation" algorithm and "two-step estimation" algorithm, to accommodate for different settings. When the proportion of permuted labels is moderate, both methods work effectively. Multiple numerical experiments are provided and corroborate our theoretical findings.

Adverse Drug Reactions (ADRs) from psychiatric medications are the leading cause of hospitalizations among mental health patients. With healthcare systems and online communities facing limitations in resolving ADR-related issues, Large Language Models (LLMs) have the potential to fill this gap. Despite the increasing capabilities of LLMs, past research has not explored their capabilities in detecting ADRs related to psychiatric medications or in providing effective harm reduction strategies. To address this, we introduce the Psych-ADR benchmark and the Adverse Drug Reaction Response Assessment (ADRA) framework to systematically evaluate LLM performance in detecting ADR expressions and delivering expert-aligned mitigation strategies. Our analyses show that LLMs struggle with understanding the nuances of ADRs and differentiating between types of ADRs. While LLMs align with experts in terms of expressed emotions and tone of the text, their responses are more complex, harder to read, and only 70.86% aligned with expert strategies. Furthermore, they provide less actionable advice by a margin of 12.32% on average. Our work provides a comprehensive benchmark and evaluation framework for assessing LLMs in strategy-driven tasks within high-risk domains.

Scientific discovery relies on scientists generating novel hypotheses that undergo rigorous experimental validation. To augment this process, we introduce an AI co-scientist, a multi-agent system built on Gemini 2.0. The AI co-scientist is intended to help uncover new, original knowledge and to formulate demonstrably novel research hypotheses and proposals, building upon prior evidence and aligned to scientist-provided research objectives and guidance. The system's design incorporates a generate, debate, and evolve approach to hypothesis generation, inspired by the scientific method and accelerated by scaling test-time compute. Key contributions include: (1) a multi-agent architecture with an asynchronous task execution framework for flexible compute scaling; (2) a tournament evolution process for self-improving hypotheses generation. Automated evaluations show continued benefits of test-time compute, improving hypothesis quality. While general purpose, we focus development and validation in three biomedical areas: drug repurposing, novel target discovery, and explaining mechanisms of bacterial evolution and anti-microbial resistance. For drug repurposing, the system proposes candidates with promising validation findings, including candidates for acute myeloid leukemia that show tumor inhibition in vitro at clinically applicable concentrations. For novel target discovery, the AI co-scientist proposed new epigenetic targets for liver fibrosis, validated by anti-fibrotic activity and liver cell regeneration in human hepatic organoids. Finally, the AI co-scientist recapitulated unpublished experimental results via a parallel in silico discovery of a novel gene transfer mechanism in bacterial evolution. These results, detailed in separate, co-timed reports, demonstrate the potential to augment biomedical and scientific discovery and usher an era of AI empowered scientists.

Biomedical data is inherently multimodal, consisting of electronic health records, medical imaging, digital pathology, genome sequencing, wearable sensors, and more. The application of artificial intelligence tools to these multifaceted sensing technologies has the potential to revolutionize the prognosis, diagnosis, and management of human health and disease. However, current approaches to biomedical AI typically only train and evaluate with one or a small set of medical modalities and tasks. This limitation hampers the development of comprehensive tools that can leverage the rich interconnected information across many heterogeneous biomedical sensors. To address this challenge, we present MultiMed, a benchmark designed to evaluate and enable large-scale learning across a wide spectrum of medical modalities and tasks. MultiMed consists of 2.56 million samples across ten medical modalities such as medical reports, pathology, genomics, and protein data, and is structured into eleven challenging tasks, including disease prognosis, protein structure prediction, and medical question answering. Using MultiMed, we conduct comprehensive experiments benchmarking state-of-the-art unimodal, multimodal, and multitask models. Our analysis highlights the advantages of training large-scale medical models across many related modalities and tasks. Moreover, MultiMed enables studies of generalization across related medical concepts, robustness to real-world noisy data and distribution shifts, and novel modality combinations to improve prediction performance. MultiMed will be publicly available and regularly updated and welcomes inputs from the community.

We study the variance of stochastic policy gradients (SPGs) with many action samples per state. We derive a many-actions optimality condition, which determines when many-actions SPG yields lower variance as compared to a single-action agent with proportionally extended trajectory. We propose Model-Based Many-Actions (MBMA), an approach leveraging dynamics models for many-actions sampling in the context of SPG. MBMA addresses issues associated with existing implementations of many-actions SPG and yields lower bias and comparable variance to SPG estimated from states in model-simulated rollouts. We find that MBMA bias and variance structure matches that predicted by theory. As a result, MBMA achieves improved sample efficiency and higher returns on a range of continuous action environments as compared to model-free, many-actions, and model-based on-policy SPG baselines.

Existing knowledge distillation methods typically work by imparting the knowledge of output logits or intermediate feature maps from the teacher network to the student network, which is very successful in multi-class single-label learning. However, these methods can hardly be extended to the multi-label learning scenario, where each instance is associated with multiple semantic labels, because the prediction probabilities do not sum to one and feature maps of the whole example may ignore minor classes in such a scenario. In this paper, we propose a novel multi-label knowledge distillation method. On one hand, it exploits the informative semantic knowledge from the logits by dividing the multi-label learning problem into a set of binary classification problems; on the other hand, it enhances the distinctiveness of the learned feature representations by leveraging the structural information of label-wise embeddings. Experimental results on multiple benchmark datasets validate that the proposed method can avoid knowledge counteraction among labels, thus achieving superior performance against diverse comparing methods. Our code is available at: https://github.com/penghui-yang/L2D

We present a model that can perform multiple vision tasks and can be adapted to other downstream tasks efficiently. Despite considerable progress in multi-task learning, most efforts focus on learning from multi-label data: a single image set with multiple task labels. Such multi-label data sets are rare, small, and expensive. We say heterogeneous to refer to image sets with different task labels, or to combinations of single-task datasets. Few have explored training on such heterogeneous datasets. General-purpose vision models are still dominated by single-task pretraining, and it remains unclear how to scale up multi-task models by leveraging mainstream vision datasets designed for different purposes. The challenges lie in managing large intrinsic differences among vision tasks, including data distribution, architectures, task-specific modules, dataset scales, and sampling strategies. To address these challenges, we propose to modify and scale up mixture-of-experts (MoE) vision transformers, so that they can simultaneously learn classification, detection, and segmentation on diverse mainstream vision datasets including ImageNet, COCO, and ADE20K. Our approach achieves comparable results to single-task state-of-the-art models and demonstrates strong generalization on downstream tasks. Due to its emergent modularity, this general-purpose model decomposes into high-performing components, efficiently adapting to downstream tasks. We can fine-tune it with fewer training parameters, fewer model parameters, and less computation. Additionally, its modularity allows for easy expansion in continual-learning-without-forgetting scenarios. Finally, these functions can be controlled and combined to meet various demands of downstream tasks.

Predicting clinical outcomes from preclinical data is essential for identifying safe and effective drug combinations. Current models rely on structural or target-based features to identify high-efficacy, low-toxicity drug combinations. However, these approaches fail to incorporate the multimodal data necessary for accurate, clinically-relevant predictions. Here, we introduce MADRIGAL, a multimodal AI model that learns from structural, pathway, cell viability, and transcriptomic data to predict drug combination effects across 953 clinical outcomes and 21842 compounds, including combinations of approved drugs and novel compounds in development. MADRIGAL uses a transformer bottleneck module to unify preclinical drug data modalities while handling missing data during training and inference--a major challenge in multimodal learning. It outperforms single-modality methods and state-of-the-art models in predicting adverse drug interactions. MADRIGAL performs virtual screening of anticancer drug combinations and supports polypharmacy management for type II diabetes and metabolic dysfunction-associated steatohepatitis (MASH). It identifies transporter-mediated drug interactions. MADRIGAL predicts resmetirom, the first and only FDA-approved drug for MASH, among therapies with the most favorable safety profile. It supports personalized cancer therapy by integrating genomic profiles from cancer patients. Using primary acute myeloid leukemia samples and patient-derived xenograft models, it predicts the efficacy of personalized drug combinations. Integrating MADRIGAL with a large language model allows users to describe clinical outcomes in natural language, improving safety assessment by identifying potential adverse interactions and toxicity risks. MADRIGAL provides a multimodal approach for designing combination therapies with improved predictive accuracy and clinical relevance.

In this technical report, we propose ChemVLM, the first open-source multimodal large language model dedicated to the fields of chemistry, designed to address the incompatibility between chemical image understanding and text analysis. Built upon the VIT-MLP-LLM architecture, we leverage ChemLLM-20B as the foundational large model, endowing our model with robust capabilities in understanding and utilizing chemical text knowledge. Additionally, we employ InternVIT-6B as a powerful image encoder. We have curated high-quality data from the chemical domain, including molecules, reaction formulas, and chemistry examination data, and compiled these into a bilingual multimodal question-answering dataset. We test the performance of our model on multiple open-source benchmarks and three custom evaluation sets. Experimental results demonstrate that our model achieves excellent performance, securing state-of-the-art results in five out of six involved tasks. Our model can be found at https://huggingface.co/AI4Chem/ChemVLM-26B.

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 years, Vision-Language-Action (VLA) models have become a vital research direction in robotics due to their impressive multimodal understanding and generalization capabilities. Despite the progress, their practical deployment is severely constrained by inference speed bottlenecks, particularly in high-frequency and dexterous manipulation tasks. While recent studies have explored Jacobi decoding as a more efficient alternative to traditional autoregressive decoding, its practical benefits are marginal due to the lengthy iterations. To address it, we introduce consistency distillation training to predict multiple correct action tokens in each iteration, thereby achieving acceleration. Besides, we design mixed-label supervision to mitigate the error accumulation during distillation. Although distillation brings acceptable speedup, we identify that certain inefficient iterations remain a critical bottleneck. To tackle this, we propose an early-exit decoding strategy that moderately relaxes convergence conditions, which further improves average inference efficiency. Experimental results show that the proposed method achieves more than 4 times inference acceleration across different baselines while maintaining high task success rates in both simulated and real-world robot tasks. These experiments validate that our approach provides an efficient and general paradigm for accelerating multimodal decision-making in robotics. Our project page is available at https://irpn-eai.github.io/CEED-VLA/.

Massively multitask neural architectures provide a learning framework for drug discovery that synthesizes information from many distinct biological sources. To train these architectures at scale, we gather large amounts of data from public sources to create a dataset of nearly 40 million measurements across more than 200 biological targets. We investigate several aspects of the multitask framework by performing a series of empirical studies and obtain some interesting results: (1) massively multitask networks obtain predictive accuracies significantly better than single-task methods, (2) the predictive power of multitask networks improves as additional tasks and data are added, (3) the total amount of data and the total number of tasks both contribute significantly to multitask improvement, and (4) multitask networks afford limited transferability to tasks not in the training set. Our results underscore the need for greater data sharing and further algorithmic innovation to accelerate the drug discovery process.

Drug-target interaction (DTI) prediction is crucial for identifying new therapeutics and detecting mechanisms of action. While structure-based methods accurately model physical interactions between a drug and its protein target, cell-based assays such as Cell Painting can better capture complex DTI interactions. This paper introduces MOTIVE, a Morphological cOmpound Target Interaction Graph dataset that comprises Cell Painting features for 11,000 genes and 3,600 compounds along with their relationships extracted from seven publicly available databases. We provide random, cold-source (new drugs), and cold-target (new genes) data splits to enable rigorous evaluation under realistic use cases. Our benchmark results show that graph neural networks that use Cell Painting features consistently outperform those that learn from graph structure alone, feature-based models, and topological heuristics. MOTIVE accelerates both graph ML research and drug discovery by promoting the development of more reliable DTI prediction models. MOTIVE resources are available at https://github.com/carpenter-singh-lab/motive.

AI-driven discovery can greatly reduce design time and enhance new therapeutics' effectiveness. Models using simulators explore broad design spaces but risk violating implicit constraints due to a lack of experimental priors. For example, in a new analysis we performed on a diverse set of models on the GuacaMol benchmark using supervised classifiers, over 60\% of molecules proposed had high probability of being mutagenic. In this work, we introduce \ourdataset, a dataset of priors for design problems extracted from literature describing compounds used in lab settings. It is constructed with LLM pipelines for discovering therapeutic entities in relevant paragraphs and summarizing information in concise fair-use facts. \ourdataset~ consists of 32.3 million pairs of natural language facts, and appropriate entity representations (i.e. SMILES or refseq IDs). To demonstrate the potential of the data, we train LLM, CLIP, and LLava architectures to reason jointly about text and design targets and evaluate on tasks from the Therapeutic Data Commons (TDC). \ourdataset~is highly effective for creating models with strong priors: in supervised prediction problems that use our data as pretraining, our best models with 15M learnable parameters outperform larger 2B TxGemma on both regression and classification TDC tasks, and perform comparably to 9B models on average. Models built with \ourdataset~can be used as constraints while optimizing for novel molecules in GuacaMol, resulting in proposals that are safer and nearly as effective. We release our dataset at https://huggingface.co/datasets/medexanon/Medex{huggingface.co/datasets/medexanon/Medex}, and will provide expanded versions as available literature grows.

The integration of Multimodal Large Language Models (MLLMs) into chemistry promises to revolutionize scientific discovery, yet their ability to comprehend the dense, graphical language of reactions within authentic literature remains underexplored. Here, we introduce RxnBench, a multi-tiered benchmark designed to rigorously evaluate MLLMs on chemical reaction understanding from scientific PDFs. RxnBench comprises two tasks: Single-Figure QA (SF-QA), which tests fine-grained visual perception and mechanistic reasoning using 1,525 questions derived from 305 curated reaction schemes, and Full-Document QA (FD-QA), which challenges models to synthesize information from 108 articles, requiring cross-modal integration of text, schemes, and tables. Our evaluation of MLLMs reveals a critical capability gap: while models excel at extracting explicit text, they struggle with deep chemical logic and precise structural recognition. Notably, models with inference-time reasoning significantly outperform standard architectures, yet none achieve 50\% accuracy on FD-QA. These findings underscore the urgent need for domain-specific visual encoders and stronger reasoning engines to advance autonomous AI chemists.

Existing action recognition methods are typically actor-specific due to the intrinsic topological and apparent differences among the actors. This requires actor-specific pose estimation (e.g., humans vs. animals), leading to cumbersome model design complexity and high maintenance costs. Moreover, they often focus on learning the visual modality alone and single-label classification whilst neglecting other available information sources (e.g., class name text) and the concurrent occurrence of multiple actions. To overcome these limitations, we propose a new approach called 'actor-agnostic multi-modal multi-label action recognition,' which offers a unified solution for various types of actors, including humans and animals. We further formulate a novel Multi-modal Semantic Query Network (MSQNet) model in a transformer-based object detection framework (e.g., DETR), characterized by leveraging visual and textual modalities to represent the action classes better. The elimination of actor-specific model designs is a key advantage, as it removes the need for actor pose estimation altogether. Extensive experiments on five publicly available benchmarks show that our MSQNet consistently outperforms the prior arts of actor-specific alternatives on human and animal single- and multi-label action recognition tasks by up to 50%. Code is made available at https://github.com/mondalanindya/MSQNet.

Pretrained neural networks have attracted significant interest in chemistry and small molecule drug design. Embeddings from these models are widely used for molecular property prediction, virtual screening, and small data learning in molecular chemistry. This study presents the most extensive comparison of such models to date, evaluating 25 models across 25 datasets. Under a fair comparison framework, we assess models spanning various modalities, architectures, and pretraining strategies. Using a dedicated hierarchical Bayesian statistical testing model, we arrive at a surprising result: nearly all neural models show negligible or no improvement over the baseline ECFP molecular fingerprint. Only the CLAMP model, which is also based on molecular fingerprints, performs statistically significantly better than the alternatives. These findings raise concerns about the evaluation rigor in existing studies. We discuss potential causes, propose solutions, and offer practical recommendations.

Multimodal Large Language Models are increasingly applied to biomedical imaging, yet scientific reasoning for microscopy remains limited by the scarcity of large-scale, high-quality training data. We introduce MicroVQA++, a three-stage, large-scale and high-quality microscopy VQA corpus derived from the BIOMEDICA archive. Stage one bootstraps supervision from expert-validated figure-caption pairs sourced from peer-reviewed articles. Stage two applies HiCQA-Graph, a novel heterogeneous graph over images, captions, and QAs that fuses NLI-based textual entailment, CLIP-based vision-language alignment, and agent signals to identify and filter inconsistent samples. Stage three uses a MultiModal Large Language Model (MLLM) agent to generate multiple-choice questions (MCQ) followed by human screening. The resulting release comprises a large training split and a human-checked test split whose Bloom's level hard-sample distribution exceeds the MicroVQA benchmark. Our work delivers (i) a quality-controlled dataset that couples expert literature with graph-based filtering and human refinement; (ii) HiCQA-Graph, the first graph that jointly models (image, caption, QA) for cross-modal consistency filtering; (iii) evidence that careful data construction enables 4B-scale MLLMs to reach competitive microscopy reasoning performance (e.g., GPT-5) and achieve state-of-the-art performance among open-source MLLMs. Code and dataset will be released after the review process concludes.

Early identification of sensitive cancer cell lines is essential for accelerating biomarker discovery and elucidating drug mechanism of action. Given the efficiency and low cost of small-scale drug screens relative to extensive omics profiling, we compared drug-response panel (DRP) descriptors against omics features for predictive capacity using gradient boosting tree models across the GDSC and CCLE drug response datasets. DRP descriptors consistently outperformed omics data across key performance metrics, with variable performance across different drugs. Using complementary explainability approaches, we confirmed known MAPK-inhibitor sensitivity signatures, and identified novel potential biomarker candidates for MEK1/2 and BTK/MNK inhibitors. Lastly, to demonstrate the utility of this approach in distinguishing phenotypes, we applied our models to the breast cancer line MCF7 versus the non-tumorigenic MCF10A, and successfully identified compounds that selectively inhibit MCF7 while sparing the non-tumorigenic MCF10A. This methodology, developed using focused drug and cell line panels, supports early-stage drug development by facilitating rational cell line selection and compound prioritisation, enabling more efficient biomarker identification and candidate assessment.

ImageNet has been arguably the most popular image classification benchmark, but it is also the one with a significant level of label noise. Recent studies have shown that many samples contain multiple classes, despite being assumed to be a single-label benchmark. They have thus proposed to turn ImageNet evaluation into a multi-label task, with exhaustive multi-label annotations per image. However, they have not fixed the training set, presumably because of a formidable annotation cost. We argue that the mismatch between single-label annotations and effectively multi-label images is equally, if not more, problematic in the training setup, where random crops are applied. With the single-label annotations, a random crop of an image may contain an entirely different object from the ground truth, introducing noisy or even incorrect supervision during training. We thus re-label the ImageNet training set with multi-labels. We address the annotation cost barrier by letting a strong image classifier, trained on an extra source of data, generate the multi-labels. We utilize the pixel-wise multi-label predictions before the final pooling layer, in order to exploit the additional location-specific supervision signals. Training on the re-labeled samples results in improved model performances across the board. ResNet-50 attains the top-1 classification accuracy of 78.9% on ImageNet with our localized multi-labels, which can be further boosted to 80.2% with the CutMix regularization. We show that the models trained with localized multi-labels also outperforms the baselines on transfer learning to object detection and instance segmentation tasks, and various robustness benchmarks. The re-labeled ImageNet training set, pre-trained weights, and the source code are available at {https://github.com/naver-ai/relabel_imagenet}.

We present a labeled large-scale, high resolution chest x-ray dataset for the automated exploration of medical images along with their associated reports. This dataset includes more than 160,000 images obtained from 67,000 patients that were interpreted and reported by radiologists at Hospital San Juan Hospital (Spain) from 2009 to 2017, covering six different position views and additional information on image acquisition and patient demography. The reports were labeled with 174 different radiographic findings, 19 differential diagnoses and 104 anatomic locations organized as a hierarchical taxonomy and mapped onto standard Unified Medical Language System (UMLS) terminology. Of these reports, 27% were manually annotated by trained physicians and the remaining set was labeled using a supervised method based on a recurrent neural network with attention mechanisms. The labels generated were then validated in an independent test set achieving a 0.93 Micro-F1 score. To the best of our knowledge, this is one of the largest public chest x-ray database suitable for training supervised models concerning radiographs, and the first to contain radiographic reports in Spanish. The PadChest dataset can be downloaded from http://bimcv.cipf.es/bimcv-projects/padchest/.

With the increasing awareness of health and the growing desire for aesthetic physique, fitness has become a prevailing trend. However, the potential risks associated with fitness training, especially with weight-loaded fitness actions, cannot be overlooked. Action Quality Assessment (AQA), a technology that quantifies the quality of human action and provides feedback, holds the potential to assist fitness enthusiasts of varying skill levels in achieving better training outcomes. Nevertheless, current AQA methodologies and datasets are limited to single-view competitive sports scenarios and RGB modality and lack professional assessment and guidance of fitness actions. To address this gap, we propose the FLEX dataset, the first multi-modal, multi-action, large-scale dataset that incorporates surface electromyography (sEMG) signals into AQA. FLEX utilizes high-precision MoCap to collect 20 different weight-loaded actions performed by 38 subjects across 3 different skill levels for 10 repetitions each, containing 5 different views of the RGB video, 3D pose, sEMG, and physiological information. Additionally, FLEX incorporates knowledge graphs into AQA, constructing annotation rules in the form of penalty functions that map weight-loaded actions, action keysteps, error types, and feedback. We conducted various baseline methodologies on FLEX, demonstrating that multimodal data, multiview data, and fine-grained annotations significantly enhance model performance. FLEX not only advances AQA methodologies and datasets towards multi-modal and multi-action scenarios but also fosters the integration of artificial intelligence within the fitness domain. Dataset and code are available at https://haoyin116.github.io/FLEX_Dataset.

Multi-label classification (MLC) requires predicting multiple labels per sample, often under heavy class imbalance and noisy conditions. Traditional approaches apply fixed thresholds or treat labels independently, overlooking context and global rarity. We introduce an adaptive thresholding mechanism that fuses global (IDF-based) and local (KNN-based) signals to produce per-label, per-instance thresholds. Instead of applying these as hard cutoffs, we treat them as differentiable penalties in the loss, providing smooth supervision and better calibration. Our architecture is lightweight, interpretable, and highly modular. On the AmazonCat-13K benchmark, it achieves a macro-F1 of 0.1712, substantially outperforming tree-based and pretrained transformer-based methods. We release full code for reproducibility and future extensions.

Deep learning methods have shown outstanding classification accuracy in medical imaging problems, which is largely attributed to the availability of large-scale datasets manually annotated with clean labels. However, given the high cost of such manual annotation, new medical imaging classification problems may need to rely on machine-generated noisy labels extracted from radiology reports. Indeed, many Chest X-ray (CXR) classifiers have already been modelled from datasets with noisy labels, but their training procedure is in general not robust to noisy-label samples, leading to sub-optimal models. Furthermore, CXR datasets are mostly multi-label, so current noisy-label learning methods designed for multi-class problems cannot be easily adapted. In this paper, we propose a new method designed for the noisy multi-label CXR learning, which detects and smoothly re-labels samples from the dataset, which is then used to train common multi-label classifiers. The proposed method optimises a bag of multi-label descriptors (BoMD) to promote their similarity with the semantic descriptors produced by BERT models from the multi-label image annotation. Our experiments on diverse noisy multi-label training sets and clean testing sets show that our model has state-of-the-art accuracy and robustness in many CXR multi-label classification benchmarks.

Recent studies have shown how disentangling images into content and feature spaces can provide controllable image translation/ manipulation. In this paper, we propose a framework to enable utilizing discrete multi-labels to control which features to be disentangled, i.e., disentangling label-specific fine-grained features for image manipulation (dubbed DLGAN). By mapping the discrete label-specific attribute features into a continuous prior distribution, we leverage the advantages of both discrete labels and reference images to achieve image manipulation in a hybrid fashion. For example, given a face image dataset (e.g., CelebA) with multiple discrete fine-grained labels, we can learn to smoothly interpolate a face image between black hair and blond hair through reference images while immediately controlling the gender and age through discrete input labels. To the best of our knowledge, this is the first work that realizes such a hybrid manipulation within a single model. More importantly, it is the first work to achieve image interpolation between two different domains without requiring continuous labels as the supervision. Qualitative and quantitative experiments demonstrate the effectiveness of the proposed method.

Large language models (LLMs) and emerging agentic frameworks are beginning to transform single-cell biology by enabling natural-language reasoning, generative annotation, and multimodal data integration. However, progress remains fragmented across data modalities, architectures, and evaluation standards. LLM4Cell presents the first unified survey of 58 foundation and agentic models developed for single-cell research, spanning RNA, ATAC, multi-omic, and spatial modalities. We categorize these methods into five families-foundation, text-bridge, spatial, multimodal, epigenomic, and agentic-and map them to eight key analytical tasks including annotation, trajectory and perturbation modeling, and drug-response prediction. Drawing on over 40 public datasets, we analyze benchmark suitability, data diversity, and ethical or scalability constraints, and evaluate models across 10 domain dimensions covering biological grounding, multi-omics alignment, fairness, privacy, and explainability. By linking datasets, models, and evaluation domains, LLM4Cell provides the first integrated view of language-driven single-cell intelligence and outlines open challenges in interpretability, standardization, and trustworthy model development.

Motivation: The development of novel compounds targeting proteins of interest is one of the most important tasks in the pharmaceutical industry. Deep generative models have been applied to targeted molecular design and have shown promising results. Recently, target-specific molecule generation has been viewed as a translation between the protein language and the chemical language. However, such a model is limited by the availability of interacting protein-ligand pairs. On the other hand, large amounts of unlabeled protein sequences and chemical compounds are available and have been used to train language models that learn useful representations. In this study, we propose exploiting pretrained biochemical language models to initialize (i.e. warm start) targeted molecule generation models. We investigate two warm start strategies: (i) a one-stage strategy where the initialized model is trained on targeted molecule generation (ii) a two-stage strategy containing a pre-finetuning on molecular generation followed by target specific training. We also compare two decoding strategies to generate compounds: beam search and sampling. Results: The results show that the warm-started models perform better than a baseline model trained from scratch. The two proposed warm-start strategies achieve similar results to each other with respect to widely used metrics from benchmarks. However, docking evaluation of the generated compounds for a number of novel proteins suggests that the one-stage strategy generalizes better than the two-stage strategy. Additionally, we observe that beam search outperforms sampling in both docking evaluation and benchmark metrics for assessing compound quality. Availability and implementation: The source code is available at https://github.com/boun-tabi/biochemical-lms-for-drug-design and the materials are archived in Zenodo at https://doi.org/10.5281/zenodo.6832145

Due to the difficulty of collecting exhaustive multi-label annotations, multi-label datasets often contain partial labels. We consider an extreme of this weakly supervised learning problem, called single positive multi-label learning (SPML), where each multi-label training image has only one positive label. Traditionally, all unannotated labels are assumed as negative labels in SPML, which introduces false negative labels and causes model training to be dominated by assumed negative labels. In this work, we choose to treat all unannotated labels from an alternative perspective, i.e. acknowledging they are unknown. Hence, we propose entropy-maximization (EM) loss to attain a special gradient regime for providing proper supervision signals. Moreover, we propose asymmetric pseudo-labeling (APL), which adopts asymmetric-tolerance strategies and a self-paced procedure, to cooperate with EM loss and then provide more precise supervision. Experiments show that our method significantly improves performance and achieves state-of-the-art results on all four benchmarks. Code is available at https://github.com/Correr-Zhou/SPML-AckTheUnknown.

Multi-omics research has enhanced our understanding of cancer heterogeneity and progression. Investigating molecular data through multi-omics approaches is crucial for unraveling the complex biological mechanisms underlying cancer, thereby enabling effective diagnosis, treatment, and prevention strategies. However, predicting patient outcomes through integration of all available multi-omics data is an under-study research direction. Here, we present SeNMo (Self-normalizing Network for Multi-omics), a deep neural network trained on multi-omics data across 33 cancer types. SeNMo is efficient in handling multi-omics data characterized by high-width (many features) and low-length (fewer samples) attributes. We trained SeNMo for the task of overall survival using pan-cancer data involving 33 cancer sites from Genomics Data Commons (GDC). The training data includes gene expression, DNA methylation, miRNA expression, DNA mutations, protein expression modalities, and clinical data. We evaluated the model's performance in predicting overall survival using concordance index (C-Index). SeNMo performed consistently well in training regime, with the validation C-Index of 0.76 on GDC's public data. In the testing regime, SeNMo performed with a C-Index of 0.758 on a held-out test set. The model showed an average accuracy of 99.8% on the task of classifying the primary cancer type on the pan-cancer test cohort. SeNMo proved to be a mini-foundation model for multi-omics oncology data because it demonstrated robust performance, and adaptability not only across molecular data types but also on the classification task of predicting the primary cancer type of patients. SeNMo can be further scaled to any cancer site and molecular data type. We believe SeNMo and similar models are poised to transform the oncology landscape, offering hope for more effective, efficient, and patient-centric cancer care.

Zero-shot action recognition (ZSAR) aims to learn an alignment model between videos and class descriptions of seen actions that is transferable to unseen actions. The text queries (class descriptions) used in existing ZSAR works, however, are often short action names that fail to capture the rich semantics in the videos, leading to misalignment. With the intuition that video content descriptions (e.g., video captions) can provide rich contextual information of visual concepts in videos, we propose to utilize human annotated video descriptions to enrich the semantics of the class descriptions of each action. However, all existing action video description datasets are limited in terms of the number of actions, the semantics of video descriptions, etc. To this end, we collect a large-scale action video descriptions dataset named ActionHub, which covers a total of 1,211 common actions and provides 3.6 million action video descriptions. With the proposed ActionHub dataset, we further propose a novel Cross-modality and Cross-action Modeling (CoCo) framework for ZSAR, which consists of a Dual Cross-modality Alignment module and a Cross-action Invariance Mining module. Specifically, the Dual Cross-modality Alignment module utilizes both action labels and video descriptions from ActionHub to obtain rich class semantic features for feature alignment. The Cross-action Invariance Mining module exploits a cycle-reconstruction process between the class semantic feature spaces of seen actions and unseen actions, aiming to guide the model to learn cross-action invariant representations. Extensive experimental results demonstrate that our CoCo framework significantly outperforms the state-of-the-art on three popular ZSAR benchmarks (i.e., Kinetics-ZSAR, UCF101 and HMDB51) under two different learning protocols in ZSAR. We will release our code, models, and the proposed ActionHub dataset.

ImageNet, an influential dataset in computer vision, is traditionally evaluated using single-label classification, which assumes that an image can be adequately described by a single concept or label. However, this approach may not fully capture the complex semantics within the images available in ImageNet, potentially hindering the development of models that effectively learn these intricacies. This study critically examines the prevalent single-label benchmarking approach and advocates for a shift to multi-label benchmarking for ImageNet. This shift would enable a more comprehensive assessment of the capabilities of deep neural network (DNN) models. We analyze the effectiveness of pre-trained state-of-the-art DNNs on ImageNet and one of its variants, ImageNetV2. Studies in the literature have reported unexpected accuracy drops of 11% to 14% on ImageNetV2. Our findings show that these reported declines are largely attributable to a characteristic of the dataset that has not received sufficient attention -- the proportion of images with multiple labels. Taking this characteristic into account, the results of our experiments provide evidence that there is no substantial degradation in effectiveness on ImageNetV2. Furthermore, we acknowledge that ImageNet pre-trained models exhibit some capability at capturing the multi-label nature of the dataset even though they were trained under the single-label assumption. Consequently, we propose a new evaluation approach to augment existing approaches that assess this capability. Our findings highlight the importance of considering the multi-label nature of the ImageNet dataset during benchmarking. Failing to do so could lead to incorrect conclusions regarding the effectiveness of DNNs and divert research efforts from addressing other substantial challenges related to the reliability and robustness of these models.

Recently, there has been significant interest in enhancing the capability of multimodal large language models (MLLMs) to process high-resolution images. Most existing methods focus on adopting a cropping strategy to improve the ability of multimodal large language models to understand image details. However, this cropping operation inevitably causes the segmentation of objects and connected areas, which impairs the MLLM's ability to recognize small or irregularly shaped objects or text. This issue is particularly evident in lightweight MLLMs. Addressing this issue, we propose Mini-Monkey, a lightweight MLLM that incorporates a plug-and-play method called multi-scale adaptive crop strategy (MSAC). Mini-Monkey adaptively generates multi-scale representations, allowing it to select non-segmented objects from various scales. To mitigate the computational overhead introduced by MSAC, we propose a Scale Compression Mechanism (SCM), which effectively compresses image tokens. Mini-Monkey achieves state-of-the-art performance among 2B-parameter MLLMs. It not only demonstrates leading performance on a variety of general multimodal understanding tasks but also shows consistent improvements in document understanding capabilities. On the OCRBench, Mini-Monkey achieves a score of 802, outperforming 8B-parameter state-of-the-art model InternVL2-8B. Besides, our model and training strategy are very efficient, which can be trained with only eight RTX 3090. The code is available at https://github.com/Yuliang-Liu/Monkey.

Molecular "fingerprints" encoding structural information are the workhorse of cheminformatics and machine learning in drug discovery applications. However, fingerprint representations necessarily emphasize particular aspects of the molecular structure while ignoring others, rather than allowing the model to make data-driven decisions. We describe molecular "graph convolutions", a machine learning architecture for learning from undirected graphs, specifically small molecules. Graph convolutions use a simple encoding of the molecular graph---atoms, bonds, distances, etc.---which allows the model to take greater advantage of information in the graph structure. Although graph convolutions do not outperform all fingerprint-based methods, they (along with other graph-based methods) represent a new paradigm in ligand-based virtual screening with exciting opportunities for future improvement.

The common toxicity and societal bias in contents generated by large language models (LLMs) necessitate strategies to reduce harm. Present solutions often demand white-box access to the model or substantial training, which is impractical for cutting-edge commercial LLMs. Moreover, prevailing prompting methods depend on external tool feedback and fail to simultaneously lessen toxicity and bias. Motivated by social psychology principles, we propose a novel strategy named perspective-taking prompting (\textsc{PeT)} that inspires LLMs to integrate diverse human perspectives and self-regulate their responses. This self-correction mechanism can significantly diminish toxicity (up to 89%) and bias (up to 73%) in LLMs' responses. Rigorous evaluations and ablation studies are conducted on two commercial LLMs (ChatGPT and GLM) and three open-source LLMs, revealing PeT's superiority in producing less harmful responses, outperforming five strong baselines.

Cancer is the second leading cause of death, with chemotherapy as one of the primary forms of treatment. As a result, researchers are turning to drug combination therapy to decrease drug resistance and increase efficacy. Current methods of drug combination screening, such as in vivo and in vitro, are inefficient due to stark time and monetary costs. In silico methods have become increasingly important for screening drugs, but current methods are inaccurate and generalize poorly to unseen anticancer drugs. In this paper, I employ a geometric deep-learning model utilizing a graph attention network that is equivariant to 3D rotations, translations, and reflections with structural motifs. Additionally, the gene expression of cancer cell lines is utilized to classify synergistic drug combinations specific to each cell line. I compared the proposed geometric deep learning framework to current state-of-the-art (SOTA) methods, and the proposed model architecture achieved greater performance on all 12 benchmark tasks performed on the DrugComb dataset. Specifically, the proposed framework outperformed other SOTA methods by an accuracy difference greater than 28%. Based on these results, I believe that the equivariant graph attention network's capability of learning geometric data accounts for the large performance improvements. The model's ability to generalize to foreign drugs is thought to be due to the structural motifs providing a better representation of the molecule. Overall, I believe that the proposed equivariant geometric deep learning framework serves as an effective tool for virtually screening anticancer drug combinations for further validation in a wet lab environment. The code for this work is made available online at: https://github.com/WeToTheMoon/EGAT_DrugSynergy.

Rapid progress in multimodal large language models (MLLMs) highlights the need to introduce challenging yet realistic benchmarks to the academic community, while existing benchmarks primarily focus on understanding simple natural images and short context. In this paper, we present MULTI as a cutting-edge benchmark for evaluating MLLMs on understanding complex tables and images, and reasoning with long context. MULTI provides multimodal inputs and requires responses that are either precise or open-ended, reflecting real-life examination styles. MULTI includes over 18,000 questions and challenges MLLMs with a variety of tasks, ranging from formula derivation to image detail analysis and cross-modality reasoning. We also introduce MULTI-Elite, a 500-question selected hard subset, and MULTI-Extend, with more than 4,500 external knowledge context pieces. Our evaluation indicates significant potential for MLLM advancement, with GPT-4V achieving a 63.7% accuracy rate on MULTI, in contrast to other MLLMs scoring between 28.5% and 55.3%. MULTI serves not only as a robust evaluation platform but also paves the way for the development of expert-level AI.

Large language models have already demonstrated their formidable capabilities in general domains, ushering in a revolutionary transformation. However, exploring and exploiting the extensive knowledge of these models to comprehend multi-omics biology remains underexplored. To fill this research gap, we first introduce Biology-Instructions, the first large-scale multi-omics biological sequences-related instruction-tuning dataset including DNA, RNA, proteins, and multi-molecules, designed to bridge the gap between large language models (LLMs) and complex biological sequences-related tasks. This dataset can enhance the versatility of LLMs by integrating diverse biological sequenced-based prediction tasks with advanced reasoning capabilities, while maintaining conversational fluency. Additionally, we reveal significant performance limitations in even state-of-the-art LLMs on biological sequence-related multi-omics tasks without specialized pre-training and instruction-tuning. We further develop a strong baseline called ChatMultiOmics with a novel three-stage training pipeline, demonstrating the powerful ability to understand biology by using Biology-Instructions. Biology-Instructions and ChatMultiOmics are publicly available and crucial resources for enabling more effective integration of LLMs with multi-omics sequence analysis.

Multimodal large language models (MLLMs) are designed to process and integrate information from multiple sources, such as text, speech, images, and videos. Despite its success in language understanding, it is critical to evaluate the performance of downstream tasks for better human-centric applications. This paper assesses the application of MLLMs with 5 crucial abilities for affective computing, spanning from visual affective tasks and reasoning tasks. The results show that \gpt has high accuracy in facial action unit recognition and micro-expression detection while its general facial expression recognition performance is not accurate. We also highlight the challenges of achieving fine-grained micro-expression recognition and the potential for further study and demonstrate the versatility and potential of \gpt for handling advanced tasks in emotion recognition and related fields by integrating with task-related agents for more complex tasks, such as heart rate estimation through signal processing. In conclusion, this paper provides valuable insights into the potential applications and challenges of MLLMs in human-centric computing. Our interesting examples are at https://github.com/EnVision-Research/GPT4Affectivity.

The growing demand for data-driven decision-making has created an urgent need for data agents that can integrate structured and unstructured data for analysis. While data agents show promise for enabling users to perform complex analytics tasks, this field still suffers from three critical limitations: first, comprehensive data agent benchmarks remain absent due to the difficulty of designing test cases that evaluate agents' abilities across multi-source analytical tasks; second, constructing reliable test cases that combine structured and unstructured data remains costly and prohibitively complex; third, existing benchmarks exhibit limited adaptability and generalizability, resulting in narrow evaluation scope. To address these challenges, we present FDABench, the first data agent benchmark specifically designed for evaluating agents in multi-source data analytical scenarios. Our contributions include: (i) we construct a standardized benchmark with 2,007 diverse tasks across different data sources, domains, difficulty levels, and task types to comprehensively evaluate data agent performance; (ii) we design an agent-expert collaboration framework ensuring reliable and efficient benchmark construction over heterogeneous data; (iii) we equip FDABench with robust generalization capabilities across diverse target systems and frameworks. We use FDABench to evaluate various data agent systems, revealing that each system exhibits distinct advantages and limitations regarding response quality, accuracy, latency, and token cost.

Efficient molecular modeling and design are crucial for the discovery and exploration of novel molecules, and the incorporation of deep learning methods has revolutionized this field. In particular, large language models (LLMs) offer a fresh approach to tackle scientific problems from a natural language processing (NLP) perspective, introducing a research paradigm called scientific language modeling (SLM). However, two key issues remain: how to quantify the match between model and data modalities and how to identify the knowledge-learning preferences of models. To address these challenges, we propose a multi-modal benchmark, named ChEBI-20-MM, and perform 1263 experiments to assess the model's compatibility with data modalities and knowledge acquisition. Through the modal transition probability matrix, we provide insights into the most suitable modalities for tasks. Furthermore, we introduce a statistically interpretable approach to discover context-specific knowledge mapping by localized feature filtering. Our pioneering analysis offers an exploration of the learning mechanism and paves the way for advancing SLM in molecular science.

Vision-Language-Action (VLA) models have shown remarkable potential in visuomotor control and instruction comprehension through end-to-end learning processes. However, current VLA models face significant challenges: they are slow during inference and require extensive pre-training on large amounts of robotic data, making real-world deployment difficult. In this paper, we introduce a new family of compact vision-language-action models, called TinyVLA, which offers two key advantages over existing VLA models: (1) faster inference speeds, and (2) improved data efficiency, eliminating the need for pre-training stage. Our framework incorporates two essential components to build TinyVLA: (1) initializing the policy backbone with robust, high-speed multimodal models, and (2) integrating a diffusion policy decoder during fine-tuning to enable precise robot actions. We conducted extensive evaluations of TinyVLA in both simulation and on real robots, demonstrating that our approach significantly outperforms the state-of-the-art VLA model, OpenVLA, in terms of speed and data efficiency, while delivering comparable or superior performance. Additionally, TinyVLA exhibits strong generalization capabilities across various dimensions, including language instructions, novel objects, unseen positions, changes in object appearance, background variations, and environmental shifts, often matching or exceeding the performance of OpenVLA. We believe that \methodname offers an interesting perspective on utilizing pre-trained multimodal models for policy learning. Our project is at https://tiny-vla.github.io.

Numerous biological and physical processes can be modeled as systems of interacting entities evolving continuously over time, e.g. the dynamics of communicating cells or physical particles. Learning the dynamics of such systems is essential for predicting the temporal evolution of populations across novel samples and unseen environments. Flow-based models allow for learning these dynamics at the population level - they model the evolution of the entire distribution of samples. However, current flow-based models are limited to a single initial population and a set of predefined conditions which describe different dynamics. We argue that multiple processes in natural sciences have to be represented as vector fields on the Wasserstein manifold of probability densities. That is, the change of the population at any moment in time depends on the population itself due to the interactions between samples. In particular, this is crucial for personalized medicine where the development of diseases and their respective treatment response depends on the microenvironment of cells specific to each patient. We propose Meta Flow Matching (MFM), a practical approach to integrating along these vector fields on the Wasserstein manifold by amortizing the flow model over the initial populations. Namely, we embed the population of samples using a Graph Neural Network (GNN) and use these embeddings to train a Flow Matching model. This gives MFM the ability to generalize over the initial distributions unlike previously proposed methods. We demonstrate the ability of MFM to improve prediction of individual treatment responses on a large scale multi-patient single-cell drug screen dataset.

In the realm of public health, vaccination stands as the cornerstone for mitigating disease risks and controlling their proliferation. The recent COVID-19 pandemic has highlighted how vaccines play a crucial role in keeping us safe. However the situation involves a mix of perspectives, with skepticism towards vaccines prevailing for various reasons such as political dynamics, apprehensions about side effects, and more. The paper addresses the challenge of comprehensively understanding and categorizing these diverse concerns expressed in the context of vaccination. Our focus is on developing a robust multi-label classifier capable of assigning specific concern labels to tweets based on the articulated apprehensions towards vaccines. To achieve this, we delve into the application of a diverse set of advanced natural language processing techniques and machine learning algorithms including transformer models like BERT, state of the art GPT 3.5, Classifier Chains & traditional methods like SVM, Random Forest, Naive Bayes. We see that the cutting-edge large language model outperforms all other methods in this context.

Multiple Instance Learning (MIL) has emerged as a dominant paradigm to extract discriminative feature representations within Whole Slide Images (WSIs) in computational pathology. Despite driving notable progress, existing MIL approaches suffer from limitations in facilitating comprehensive and efficient interactions among instances, as well as challenges related to time-consuming computations and overfitting. In this paper, we incorporate the Selective Scan Space State Sequential Model (Mamba) in Multiple Instance Learning (MIL) for long sequence modeling with linear complexity, termed as MambaMIL. By inheriting the capability of vanilla Mamba, MambaMIL demonstrates the ability to comprehensively understand and perceive long sequences of instances. Furthermore, we propose the Sequence Reordering Mamba (SR-Mamba) aware of the order and distribution of instances, which exploits the inherent valuable information embedded within the long sequences. With the SR-Mamba as the core component, MambaMIL can effectively capture more discriminative features and mitigate the challenges associated with overfitting and high computational overhead. Extensive experiments on two public challenging tasks across nine diverse datasets demonstrate that our proposed framework performs favorably against state-of-the-art MIL methods. The code is released at https://github.com/isyangshu/MambaMIL.

Medical systematic reviews can be very costly and resource intensive. We explore how Large Language Models (LLMs) can support and be trained to perform literature screening when provided with a detailed set of selection criteria. Specifically, we instruction tune LLaMA and Guanaco models to perform abstract screening for medical systematic reviews. Our best model, Bio-SIEVE, outperforms both ChatGPT and trained traditional approaches, and generalises better across medical domains. However, there remains the challenge of adapting the model to safety-first scenarios. We also explore the impact of multi-task training with Bio-SIEVE-Multi, including tasks such as PICO extraction and exclusion reasoning, but find that it is unable to match single-task Bio-SIEVE's performance. We see Bio-SIEVE as an important step towards specialising LLMs for the biomedical systematic review process and explore its future developmental opportunities. We release our models, code and a list of DOIs to reconstruct our dataset for reproducibility.

The Russian Drug Reaction Corpus (RuDReC) is a new partially annotated corpus of consumer reviews in Russian about pharmaceutical products for the detection of health-related named entities and the effectiveness of pharmaceutical products. The corpus itself consists of two parts, the raw one and the labelled one. The raw part includes 1.4 million health-related user-generated texts collected from various Internet sources, including social media. The labelled part contains 500 consumer reviews about drug therapy with drug- and disease-related information. Labels for sentences include health-related issues or their absence. The sentences with one are additionally labelled at the expression level for identification of fine-grained subtypes such as drug classes and drug forms, drug indications, and drug reactions. Further, we present a baseline model for named entity recognition (NER) and multi-label sentence classification tasks on this corpus. The macro F1 score of 74.85% in the NER task was achieved by our RuDR-BERT model. For the sentence classification task, our model achieves the macro F1 score of 68.82% gaining 7.47% over the score of BERT model trained on Russian data. We make the RuDReC corpus and pretrained weights of domain-specific BERT models freely available at https://github.com/cimm-kzn/RuDReC

Over the last decades, excellent computational chemistry tools have been developed. Their full potential has not yet been reached as most are challenging to learn and exist in isolation. Recently, large-language models (LLMs) have shown strong performance in tasks across domains, but struggle with chemistry-related problems. Moreover, these models lack access to external knowledge sources, limiting their usefulness in scientific applications. In this study, we introduce ChemCrow, an LLM chemistry agent designed to accomplish tasks across organic synthesis, drug discovery, and materials design. By integrating 17 expert-designed tools, ChemCrow augments the LLM performance in chemistry, and new capabilities emerge. Our agent autonomously planned the syntheses of an insect repellent, three organocatalysts, as well as other relevant molecules. Our evaluation, including both LLM and expert assessments, demonstrates ChemCrow's effectiveness in automating a diverse set of chemical tasks. Surprisingly, we find that GPT-4 as an evaluator cannot distinguish between clearly wrong GPT-4 completions and Chemcrow's performance. There is a significant risk of misuse of tools like ChemCrow, and we discuss their potential harms. Employed responsibly, our work not only aids expert chemists and lowers barriers for non-experts, but also fosters scientific advancement by bridging the gap between experimental and computational chemistry. A subset of the code is publicly available at https://github.com/ur-whitelab/chemcrow-public.

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}.

Generative models for structure-based drug design (SBDD) have shown promising results in recent years. Existing works mainly focus on how to generate molecules with higher binding affinity, ignoring the feasibility prerequisites for generated 3D poses and resulting in false positives. We conduct thorough studies on key factors of ill-conformational problems when applying autoregressive methods and diffusion to SBDD, including mode collapse and hybrid continuous-discrete space. In this paper, we introduce MolCRAFT, the first SBDD model that operates in the continuous parameter space, together with a novel noise reduced sampling strategy. Empirical results show that our model consistently achieves superior performance in binding affinity with more stable 3D structure, demonstrating our ability to accurately model interatomic interactions. To our best knowledge, MolCRAFT is the first to achieve reference-level Vina Scores (-6.59 kcal/mol) with comparable molecular size, outperforming other strong baselines by a wide margin (-0.84 kcal/mol). Code is available at https://github.com/AlgoMole/MolCRAFT.

High-throughput reaction condition (RC) screening is fundamental to chemical synthesis. However, current RC screening suffers from laborious and costly trial-and-error workflows. Traditional computer-aided synthesis planning (CASP) tools fail to find suitable RCs due to data sparsity and inadequate reaction representations. Nowadays, large language models (LLMs) are capable of tackling chemistry-related problems, such as molecule design, and chemical logic Q\&A tasks. However, LLMs have not yet achieved accurate predictions of chemical reaction conditions. Here, we present MM-RCR, a text-augmented multimodal LLM that learns a unified reaction representation from SMILES, reaction graphs, and textual corpus for chemical reaction recommendation (RCR). To train MM-RCR, we construct 1.2 million pair-wised Q\&A instruction datasets. Our experimental results demonstrate that MM-RCR achieves state-of-the-art performance on two open benchmark datasets and exhibits strong generalization capabilities on out-of-domain (OOD) and High-Throughput Experimentation (HTE) datasets. MM-RCR has the potential to accelerate high-throughput condition screening in chemical synthesis.

Recent advances in language models have enabled framing molecule generation as sequence modeling. However, existing approaches often rely on single-objective reinforcement learning, limiting their applicability to real-world drug design, where multiple competing properties must be optimized. Traditional multi-objective reinforcement learning (MORL) methods require costly retraining for each new objective combination, making rapid exploration of trade-offs impractical. To overcome these limitations, we introduce Mol-MoE, a mixture-of-experts (MoE) architecture that enables efficient test-time steering of molecule generation without retraining. Central to our approach is a preference-based router training objective that incentivizes the router to combine experts in a way that aligns with user-specified trade-offs. This provides improved flexibility in exploring the chemical property space at test time, facilitating rapid trade-off exploration. Benchmarking against state-of-the-art methods, we show that Mol-MoE achieves superior sample quality and steerability.

Drug discovery is a complex and resource-intensive process, making early prediction of approval outcomes critical for optimizing research investments. While classical machine learning and deep learning methods have shown promise in drug approval prediction, their limited interpretability constraints their impact. Here, we present DrugReasoner, a reasoning-based large language model (LLM) built on the LLaMA architecture and fine-tuned with group relative policy optimization (GRPO) to predict the likelihood of small-molecule approval. DrugReasoner integrates molecular descriptors with comparative reasoning against structurally similar approved and unapproved compounds, generating predictions alongside step-by-step rationales and confidence scores. DrugReasoner achieved robust performance with an AUC of 0.732 and an F1 score of 0.729 on the validation set and 0.725 and 0.718 on the test set, respectively. These results outperformed conventional baselines, including logistic regression, support vector machine, and k-nearest neighbors and had competitive performance relative to XGBoost. On an external independent dataset, DrugReasoner outperformed both baseline and the recently developed ChemAP model, achieving an AUC of 0.728 and an F1-score of 0.774, while maintaining high precision and balanced sensitivity, demonstrating robustness in real-world scenarios. These findings demonstrate that DrugReasoner not only delivers competitive predictive accuracy but also enhances transparency through its reasoning outputs, thereby addressing a key bottleneck in AI-assisted drug discovery. This study highlights the potential of reasoning-augmented LLMs as interpretable and effective tools for pharmaceutical decision-making.

Recent research in representation learning utilizes large databases of proteins or molecules to acquire knowledge of drug and protein structures through unsupervised learning techniques. These pre-trained representations have proven to significantly enhance the accuracy of subsequent tasks, such as predicting the affinity between drugs and target proteins. In this study, we demonstrate that by incorporating knowledge graphs from diverse sources and modalities into the sequences or SMILES representation, we can further enrich the representation and achieve state-of-the-art results on established benchmark datasets. We provide preprocessed and integrated data obtained from 7 public sources, which encompass over 30M triples. Additionally, we make available the pre-trained models based on this data, along with the reported outcomes of their performance on three widely-used benchmark datasets for drug-target binding affinity prediction found in the Therapeutic Data Commons (TDC) benchmarks. Additionally, we make the source code for training models on benchmark datasets publicly available. Our objective in releasing these pre-trained models, accompanied by clean data for model pretraining and benchmark results, is to encourage research in knowledge-enhanced representation learning.

As a key component in boosting online user growth, uplift modeling aims to measure individual user responses (e.g., whether to play the game) to various treatments, such as gaming bonuses, thereby enhancing business outcomes. However, previous research typically considers a single-task, single-treatment setting, where only one treatment exists and the overall treatment effect is measured by a single type of user response. In this paper, we propose a Multi-Treatment Multi-Task (MTMT) uplift network to estimate treatment effects in a multi-task scenario. We identify the multi-treatment problem as a causal inference problem with a tiered response, comprising a base effect (from offering a treatment) and an incremental effect (from offering a specific type of treatment), where the base effect can be numerically much larger than the incremental effect. Specifically, MTMT separately encodes user features and treatments. The user feature encoder uses a multi-gate mixture of experts (MMOE) network to encode relevant user features, explicitly learning inter-task relations. The resultant embeddings are used to measure natural responses per task. Furthermore, we introduce a treatment-user feature interaction module to model correlations between each treatment and user feature. Consequently, we separately measure the base and incremental treatment effect for each task based on the produced treatment-aware representations. Experimental results based on an offline public dataset and an online proprietary dataset demonstrate the effectiveness of MTMT in single/multi-treatment and single/multi-task settings. Additionally, MTMT has been deployed in our gaming platform to improve user experience.

Multimodal large language models (MLLMs) have made impressive progress in many applications in recent years. However, chemical MLLMs that can handle cross-modal understanding and generation remain underexplored. To fill this gap, in this paper, we propose ChemMLLM, a unified chemical multimodal large language model for molecule understanding and generation. Also, we design five multimodal tasks across text, molecular SMILES strings, and image, and curate the datasets. We benchmark ChemMLLM against a range of general leading MLLMs and Chemical LLMs on these tasks. Experimental results show that ChemMLLM achieves superior performance across all evaluated tasks. For example, in molecule image optimization task, ChemMLLM outperforms the best baseline (GPT-4o) by 118.9\% (4.27 vs 1.95 property improvement). The code is publicly available at https://github.com/bbsbz/ChemMLLM.git.

Recent advances in microscopy have enabled the rapid generation of terabytes of image data in cell biology and biomedical research. Vision-language models (VLMs) offer a promising solution for large-scale biological image analysis, enhancing researchers' efficiency, identifying new image biomarkers, and accelerating hypothesis generation and scientific discovery. However, there is a lack of standardized, diverse, and large-scale vision-language benchmarks to evaluate VLMs' perception and cognition capabilities in biological image understanding. To address this gap, we introduce {\mu}-Bench, an expert-curated benchmark encompassing 22 biomedical tasks across various scientific disciplines (biology, pathology), microscopy modalities (electron, fluorescence, light), scales (subcellular, cellular, tissue), and organisms in both normal and abnormal states. We evaluate state-of-the-art biomedical, pathology, and general VLMs on {\mu}-Bench and find that: i) current models struggle on all categories, even for basic tasks such as distinguishing microscopy modalities; ii) current specialist models fine-tuned on biomedical data often perform worse than generalist models; iii) fine-tuning in specific microscopy domains can cause catastrophic forgetting, eroding prior biomedical knowledge encoded in their base model. iv) weight interpolation between fine-tuned and pre-trained models offers one solution to forgetting and improves general performance across biomedical tasks. We release {\mu}-Bench under a permissive license to accelerate the research and development of microscopy foundation models.

Learning the response of single-cells to various treatments offers great potential to enable targeted therapies. In this context, neural optimal transport (OT) has emerged as a principled methodological framework because it inherently accommodates the challenges of unpaired data induced by cell destruction during data acquisition. However, most existing OT approaches are incapable of conditioning on different treatment contexts (e.g., time, drug treatment, drug dosage, or cell type) and we still lack methods that unanimously show promising generalization performance to unseen treatments. Here, we propose the Conditional Monge Gap which learns OT maps conditionally on arbitrary covariates. We demonstrate its value in predicting single-cell perturbation responses conditional to one or multiple drugs, a drug dosage, or combinations thereof. We find that our conditional models achieve results comparable and sometimes even superior to the condition-specific state-of-the-art on scRNA-seq as well as multiplexed protein imaging data. Notably, by aggregating data across conditions we perform cross-task learning which unlocks remarkable generalization abilities to unseen drugs or drug dosages, widely outperforming other conditional models in capturing heterogeneity (i.e., higher moments) in the perturbed population. Finally, by scaling to hundreds of conditions and testing on unseen drugs, we narrow the gap between structure-based and effect-based drug representations, suggesting a promising path to the successful prediction of perturbation effects for unseen treatments.

Generative models for structure-based drug design are often limited to a specific modality, restricting their broader applicability. To address this challenge, we introduce FuncBind, a framework based on computer vision to generate target-conditioned, all-atom molecules across atomic systems. FuncBind uses neural fields to represent molecules as continuous atomic densities and employs score-based generative models with modern architectures adapted from the computer vision literature. This modality-agnostic representation allows a single unified model to be trained on diverse atomic systems, from small to large molecules, and handle variable atom/residue counts, including non-canonical amino acids. FuncBind achieves competitive in silico performance in generating small molecules, macrocyclic peptides, and antibody complementarity-determining region loops, conditioned on target structures. FuncBind also generated in vitro novel antibody binders via de novo redesign of the complementarity-determining region H3 loop of two chosen co-crystal structures. As a final contribution, we introduce a new dataset and benchmark for structure-conditioned macrocyclic peptide generation. The code is available at https://github.com/prescient-design/funcbind.

To effectively optimize and personalize treatments, it is necessary to investigate the heterogeneity of treatment effects. With the wide range of users being treated over many online controlled experiments, the typical approach of manually investigating each dimension of heterogeneity becomes overly cumbersome and prone to subjective human biases. We need an efficient way to search through thousands of experiments with hundreds of target covariates and hundreds of breakdown dimensions. In this paper, we propose a systematic paradigm for detecting, surfacing and characterizing heterogeneous treatment effects. First, we detect if treatment effect variation is present in an experiment, prior to specifying any breakdowns. Second, we surface the most relevant dimensions for heterogeneity. Finally, we characterize the heterogeneity beyond just the conditional average treatment effects (CATE) by studying the conditional distributions of the estimated individual treatment effects. We show the effectiveness of our methods using simulated data and empirical studies.

Multi-Modal Large Language Models (MLLMs), despite being successful, exhibit limited generality and often fall short when compared to specialized models. Recently, LLM-based agents have been developed to address these challenges by selecting appropriate specialized models as tools based on user inputs. However, such advancements have not been extensively explored within the medical domain. To bridge this gap, this paper introduces the first agent explicitly designed for the medical field, named Multi-modal Medical Agent (MMedAgent). We curate an instruction-tuning dataset comprising six medical tools solving seven tasks across five modalities, enabling the agent to choose the most suitable tools for a given task. Comprehensive experiments demonstrate that MMedAgent achieves superior performance across a variety of medical tasks compared to state-of-the-art open-source methods and even the closed-source model, GPT-4o. Furthermore, MMedAgent exhibits efficiency in updating and integrating new medical tools. Codes and models are all available.

Multi-label image classification is a prediction task that aims to identify more than one label from a given image. This paper considers the semantic consistency of the latent space between the visual patch and linguistic label domains and introduces the conditional transport (CT) theory to bridge the acknowledged gap. While recent cross-modal attention-based studies have attempted to align such two representations and achieved impressive performance, they required carefully-designed alignment modules and extra complex operations in the attention computation. We find that by formulating the multi-label classification as a CT problem, we can exploit the interactions between the image and label efficiently by minimizing the bidirectional CT cost. Specifically, after feeding the images and textual labels into the modality-specific encoders, we view each image as a mixture of patch embeddings and a mixture of label embeddings, which capture the local region features and the class prototypes, respectively. CT is then employed to learn and align those two semantic sets by defining the forward and backward navigators. Importantly, the defined navigators in CT distance model the similarities between patches and labels, which provides an interpretable tool to visualize the learned prototypes. Extensive experiments on three public image benchmarks show that the proposed model consistently outperforms the previous methods.

The rapid growth of biomedical knowledge has outpaced our ability to efficiently extract insights and generate novel hypotheses. Large language models (LLMs) have emerged as a promising tool to revolutionize knowledge interaction and potentially accelerate biomedical discovery. In this paper, we present a comprehensive evaluation of LLMs as biomedical hypothesis generators. We construct a dataset of background-hypothesis pairs from biomedical literature, carefully partitioned into training, seen, and unseen test sets based on publication date to mitigate data contamination. Using this dataset, we assess the hypothesis generation capabilities of top-tier instructed models in zero-shot, few-shot, and fine-tuning settings. To enhance the exploration of uncertainty, a crucial aspect of scientific discovery, we incorporate tool use and multi-agent interactions in our evaluation framework. Furthermore, we propose four novel metrics grounded in extensive literature review to evaluate the quality of generated hypotheses, considering both LLM-based and human assessments. Our experiments yield two key findings: 1) LLMs can generate novel and validated hypotheses, even when tested on literature unseen during training, and 2) Increasing uncertainty through multi-agent interactions and tool use can facilitate diverse candidate generation and improve zero-shot hypothesis generation performance. However, we also observe that the integration of additional knowledge through few-shot learning and tool use may not always lead to performance gains, highlighting the need for careful consideration of the type and scope of external knowledge incorporated. These findings underscore the potential of LLMs as powerful aids in biomedical hypothesis generation and provide valuable insights to guide further research in this area.

High-throughput screening techniques are commonly used to obtain large quantities of data in many fields of biology. It is well known that artifacts arising from variability in the technical execution of different experimental batches within such screens confound these observations and can lead to invalid biological conclusions. It is therefore necessary to account for these batch effects when analyzing outcomes. In this paper we describe RxRx1, a biological dataset designed specifically for the systematic study of batch effect correction methods. The dataset consists of 125,510 high-resolution fluorescence microscopy images of human cells under 1,138 genetic perturbations in 51 experimental batches across 4 cell types. Visual inspection of the images alone clearly demonstrates significant batch effects. We propose a classification task designed to evaluate the effectiveness of experimental batch correction methods on these images and examine the performance of a number of correction methods on this task. Our goal in releasing RxRx1 is to encourage the development of effective experimental batch correction methods that generalize well to unseen experimental batches. The dataset can be downloaded at https://rxrx.ai.

Recent progress in multimodal large language models (MLLMs) has demonstrated promising performance on medical benchmarks and in preliminary trials as clinical assistants. Yet, our pilot audit of diagnostic cases uncovers a critical failure mode: instability in early evidence interpretation precedes hallucination, creating branching reasoning trajectories that cascade into globally inconsistent conclusions. This highlights the need for clinical reasoning agents that constrain stochasticity and hallucination while producing auditable decision flows. We introduce MedMMV, a controllable multimodal multi-agent framework for reliable and verifiable clinical reasoning. MedMMV stabilizes reasoning through diversified short rollouts, grounds intermediate steps in a structured evidence graph under the supervision of a Hallucination Detector, and aggregates candidate paths with a Combined Uncertainty scorer. On six medical benchmarks, MedMMV improves accuracy by up to 12.7% and, more critically, demonstrates superior reliability. Blind physician evaluations confirm that MedMMV substantially increases reasoning truthfulness without sacrificing informational content. By controlling instability through a verifiable, multi-agent process, our framework provides a robust path toward deploying trustworthy AI systems in high-stakes domains like clinical decision support.

Machine learning (ML) models hold the promise of transforming atomic simulations by delivering quantum chemical accuracy at a fraction of the computational cost. Realization of this potential would enable high-throughout, high-accuracy molecular screening campaigns to explore vast regions of chemical space and facilitate ab initio simulations at sizes and time scales that were previously inaccessible. However, a fundamental challenge to creating ML models that perform well across molecular chemistry is the lack of comprehensive data for training. Despite substantial efforts in data generation, no large-scale molecular dataset exists that combines broad chemical diversity with a high level of accuracy. To address this gap, Meta FAIR introduces Open Molecules 2025 (OMol25), a large-scale dataset composed of more than 100 million density functional theory (DFT) calculations at the omegaB97M-V/def2-TZVPD level of theory, representing billions of CPU core-hours of compute. OMol25 uniquely blends elemental, chemical, and structural diversity including: 83 elements, a wide-range of intra- and intermolecular interactions, explicit solvation, variable charge/spin, conformers, and reactive structures. There are ~83M unique molecular systems in OMol25 covering small molecules, biomolecules, metal complexes, and electrolytes, including structures obtained from existing datasets. OMol25 also greatly expands on the size of systems typically included in DFT datasets, with systems of up to 350 atoms. In addition to the public release of the data, we provide baseline models and a comprehensive set of model evaluations to encourage community engagement in developing the next-generation ML models for molecular chemistry.

Recent advancements in AI agents have demonstrated their growing potential to drive and support scientific discovery. In this work, we introduce MLR-Bench, a comprehensive benchmark for evaluating AI agents on open-ended machine learning research. MLR-Bench includes three key components: (1) 201 research tasks sourced from NeurIPS, ICLR, and ICML workshops covering diverse ML topics; (2) MLR-Judge, an automated evaluation framework combining LLM-based reviewers with carefully designed review rubrics to assess research quality; and (3) MLR-Agent, a modular agent scaffold capable of completing research tasks through four stages: idea generation, proposal formulation, experimentation, and paper writing. Our framework supports both stepwise assessment across these distinct research stages, and end-to-end evaluation of the final research paper. We then use MLR-Bench to evaluate six frontier LLMs and an advanced coding agent, finding that while LLMs are effective at generating coherent ideas and well-structured papers, current coding agents frequently (e.g., in 80% of the cases) produce fabricated or invalidated experimental results--posing a major barrier to scientific reliability. We validate MLR-Judge through human evaluation, showing high agreement with expert reviewers, supporting its potential as a scalable tool for research evaluation. We open-source MLR-Bench to help the community benchmark, diagnose, and improve AI research agents toward trustworthy and transparent scientific discovery.

Combination therapies have become the standard of care for diseases such as cancer, tuberculosis, malaria and HIV. However, the combinatorial set of available multi-drug treatments creates a challenge in identifying effective combination therapies available in a situation. To assist medical professionals in identifying beneficial drug-combinations, we construct an expert-annotated dataset for extracting information about the efficacy of drug combinations from the scientific literature. Beyond its practical utility, the dataset also presents a unique NLP challenge, as the first relation extraction dataset consisting of variable-length relations. Furthermore, the relations in this dataset predominantly require language understanding beyond the sentence level, adding to the challenge of this task. We provide a promising baseline model and identify clear areas for further improvement. We release our dataset, code, and baseline models publicly to encourage the NLP community to participate in this task.

While various models and computational tools have been proposed for structure and property analysis of molecules, generating molecules that conform to all desired structures and properties remains a challenge. Here, we introduce a multi-constraint molecular generation large language model, TSMMG, which, akin to a student, incorporates knowledge from various small models and tools, namely, the 'teachers'. To train TSMMG, we construct a large set of text-molecule pairs by extracting molecular knowledge from these 'teachers', enabling it to generate novel molecules that conform to the descriptions through various text prompts. We experimentally show that TSMMG remarkably performs in generating molecules meeting complex, natural language-described property requirements across two-, three-, and four-constraint tasks, with an average molecular validity of over 99% and success ratio of 82.58%, 68.03%, and 67.48%, respectively. The model also exhibits adaptability through zero-shot testing, creating molecules that satisfy combinations of properties that have not been encountered. It can comprehend text inputs with various language styles, extending beyond the confines of outlined prompts, as confirmed through empirical validation. Additionally, the knowledge distillation feature of TSMMG contributes to the continuous enhancement of small models, while the innovative approach to dataset construction effectively addresses the issues of data scarcity and quality, which positions TSMMG as a promising tool in the domains of drug discovery and materials science.