arXiv subjects

Shanghua Gao

Publications and source records attributed to Shanghua Gao.

At least 19 recordsLinked to original sources

arXiv2026

Qworld: Question-Specific Evaluation Criteria for LLMs

Evaluating large language models (LLMs) on open-ended questions is difficult because response quality depends on the question's context. Binary scores and static rubrics fail to capture these context-dependent requirements. Existing methods define criteria at the dataset level or generate them in a single pass, which limits their ability to explore the evaluation space implied by each question. We introduce One-Question-One-World (Qworld), a method that generates question-specific evaluation criteria using a recursive expansion tree. Given a question, Qworld decomposes it into scenarios, perspectives, and fine-grained binary criteria through hierarchical and horizontal expansion. The resulting criteria specify what a high-quality answer must address for that question. On HealthBench, Qworld covers 89% of expert-authored criteria and generates 79% novel criteria validated by human experts. Experts rate Qworld criteria higher in insight and granularity than those produced by prior methods. When applied to 11 frontier LLMs on HealthBench and Humanity's Last Exam, Qworld reveals capability differences in dimensions such as long-term impact, equity, error handling, and interdisciplinary reasoning that coarse rubrics do not capture. By generating evaluation criteria for each question, Qworld enables assessment of LLM responses that is tailored to the question rather than based on fixed task-level criteria.

cs.CL↗

arXiv2026

Do LLMs Know What to Ask and When? Evaluating Multi-Turn Information Seeking

When a user question is underspecified, a capable model should recognize that its context is insufficient, identify the missing information, ask for it, and respond only once that information determines a unique answer. We formalize multi-turn information seeking as solving a k-underspecified constraint satisfaction problem, where k is the number of variables jointly required to determine the target and therefore measures the degree of missing information. We instantiate the formulation in MT-InfoSeek, a controlled evaluation suite of 5,251 problems and 9,006 task instances spanning mathematics, logic, biology, medicine, and general knowledge. We evaluate models along three axes: what they ask, when they ask it, and how the acquired information affects the final answer. Performance degrades across models and domains as underspecification increases. Models recognize that additional information is needed but underestimate how much, and in logical problems at k = 2 they under-predict the degree of missing information about four times as often as they over-predict it. They also fail to identify a minimal sufficient set of queries, improve only marginally when given the true k, and often stop before acquiring sufficient information. In tasks with ordered dependencies, an incorrect query order reduces final accuracy even when the model eventually acquires all necessary information. We measure information seeking directly through final sufficiency, which records whether the acquired information determines the target independent of answer generation. This separation shows differences between models that final accuracy alone does not capture, and indicates that the ability to seek information over multiple turns is distinct from the ability to generate answers and is not measured by current LLM evaluations.

cs.AI↗

arXiv2026

ToolUniverse: An open platform for democratizing AI scientists

AI scientists are emerging computational systems that serve as collaborative partners in discovery. These systems remain difficult to build because they are bespoke, tied to rigid workflows, and lack shared environments that unify tools, data, and analyses into a common ecosystem. We present ToolUniverse, an open platform for building AI scientists from any language or reasoning model across open- and closed-weight models. ToolUniverse standardizes how AI scientists identify and call tools through an AI-tool interaction standard, in which every tool declares its purpose in natural language, a typed schema for its inputs and outputs, and a backend-agnostic invocation format, and applies that standard to more than 2,700 scientific tools and over 130 research skills spanning machine learning models, datasets, APIs, and scientific packages for data analysis, knowledge retrieval, and experimental design. It automatically refines tool interfaces for correct use by AI scientists, generates new tools from natural language descriptions, iteratively optimizes tool specifications, and composes tools into agentic workflows. In case studies, ToolUniverse was used to create AI scientists that carried out end-to-end analyses in target assessment, chemical strategy, and clinical-trial safety. The open-source ToolUniverse is available at https://aiscientist.tools.

cs.AI↗

arXiv2026

An AI agent for treatment reasoning over a biomedical tool universe

Treatment reasoning underpins every therapeutic decision, integrating disease context, comorbidities, medications, contraindications, and evolving biomedical knowledge to select an appropriate therapy. It is inherently iterative: candidates are weighed against many constraints, revised as evidence emerges, and grounded in verifiable sources. Here we introduce ATHENA-R1, an AI agent for treatment reasoning across all FDA approved drugs since 1939, trained by reinforcement learning over a universe of 212 biomedical tools. At each step it identifies missing information, selects and runs relevant tools, and incorporates the evidence. To train it without human-annotated traces, we build a two-level self-learning framework: multi-agent systems construct the tools, tasks, and reasoning trajectories for supervised fine-tuning, then reinforcement learning with scientific feedback rewards reasoning quality (evidence gathering, grounded tool use, logical non-redundancy). Across five benchmarks of 3,168 drug reasoning tasks and 456 patient treatment cases, ATHENA-R1 outperforms language models and tool-use systems, reaching 94.7% accuracy on open-ended drug reasoning and 82.9% on treatment reasoning, 17.8 and 10.7 points above GPT-5. In blinded evaluations by experts from 28 rare disease organizations, it is preferred over reference models on all criteria, and physicians rated it favorably on complex hospitalized cardiovascular and infectious-disease cases. Adverse-event hypotheses it generated, tested in electronic health records from 5.4 million patients, reached adjusted odds ratios of 1.48-1.84, with no elevation among negative controls. Because it requires knowing what evidence to seek before concluding, treatment reasoning has long been hard for AI; we show it can be reframed as a learnable process of iterative evidence gathering that reinforcement learning can train AI to perform.

cs.AI↗

arXiv2026

AutoScientists: Self-Organizing Agent Teams for Long-Running Scientific Experimentation

Scientific research proceeds through iterative cycles of hypothesis generation, experiment design, execution, and revision. AI agents can automate parts of this process, but existing approaches typically follow a single research trajectory or coordinate through a central planner with fixed objectives. As a result, they struggle to sustain parallel exploration, adapt as experimental evidence changes, or preserve knowledge of failed directions over long-running experiments. We introduce AutoScientists, a decentralized team of AI agents for long-running computational scientific experimentation. Agents interpret a shared experimental state, self-organize into teams around promising hypotheses, critique proposals before using experimental compute, and share successes and failures to reduce redundant exploration. Under matched experimental budgets, AutoScientists improves over prior AI agents across biomedical machine learning, language-model training optimization, and protein fitness prediction. On BioML-Bench, spanning biomedical imaging, protein engineering, single-cell omics, and drug discovery, AutoScientists achieves a mean leaderboard percentile of 74.4% across 24 tasks, improving over the strongest AI agent by +8.33%. On GPT training optimization, AutoScientists reaches a target validation bits-per-byte 1.9x faster than Autoresearch and continues discovering improvements from a starting champion where the single-agent approach finds none (7 vs. 0 accepted improvements). On ProteinGym fitness prediction, AutoScientists discovers a method for ACE2-Spike binding that improves over the current state-of-the-art model by +12.5% in Spearman correlation. Applied without modification across all 217 ProteinGym assays, the same method improves over the prior state of the art by +6.5% (Spearman correlation).

cs.AI↗

arXiv2026

YAC: Bridging Natural Language and Interactive Visual Exploration with Generative AI for Biomedical Data Discovery

Incorporating natural language input has the potential to improve the capabilities of biomedical data discovery interfaces. However, user interface elements and visualizations are still powerful tools for interacting with data. In our prototype system, YAC, Yet Another Chatbot, we integrate natural language and interactive visualizations. YAC uses a tool-calling multi-agent system to generate declarative output, which is interpreted to render linked interactive visualizations and apply data filters. We also include adjustment widgets, which allow users to directly modify the structured output. Structured text is also generated to clarify user intent, notify users of system boundaries, and explain aspects of the data with live data element links. We conducted a user study with domain experts to surface areas where YAC can be improved. Furthermore we reflect on the capabilities and design of this system with an analysis of its technical dimensions.

cs.HC↗

arXiv2026

When Sensors Fail: Temporal Sequence Models for Robust PPO under Sensor Drift

Real-world reinforcement learning systems must operate under distributional drift in their observation streams, yet most policy architectures implicitly assume fully observed and noise-free states. We study robustness of Proximal Policy Optimization (PPO) under temporally persistent sensor failures that induce partial observability and representation shift. To respond to this drift, we augment PPO with temporal sequence models, including Transformers and State Space Models (SSMs), to enable policies to infer missing information from history and maintain performance. Under a stochastic sensor failure process, we prove a high-probability bound on infinite-horizon reward degradation that quantifies how robustness depends on policy smoothness and failure persistence. Empirically, on MuJoCo continuous-control benchmarks with severe sensor dropout, we show Transformer-based sequence policies substantially outperform MLP, RNN, and SSM baselines in robustness, maintaining high returns even when large fractions of sensors are unavailable. These results demonstrate that temporal sequence reasoning provides a principled and practical mechanism for reliable operation under observation drift caused by sensor unreliability.

cs.LG↗

arXiv2026

STRAND: Sequence-Conditioned Transport for Single-Cell Perturbations

Predicting how genetic perturbations change cellular state is a core problem for building controllable models of gene regulation. Perturbations targeting the same gene can produce different transcriptional responses depending on their genomic locus, including different transcription start sites and regulatory elements. Gene-level perturbation models collapse these distinct interventions into the same representation. We introduce STRAND, a generative model that predicts single-cell transcriptional responses by conditioning on regulatory DNA sequence. STRAND represents a perturbation by encoding the sequence at its genomic locus and uses this representation to parameterize a conditional transport process from control to perturbed cell states. Representing perturbations by sequence, rather than by a fixed set of gene identifiers, supports zero-shot inference at loci not seen during training and expands inference-time genomic coverage from ~1.5% for gene-level single-cell foundation models to ~95% of the genome. We evaluate STRAND on CRISPR perturbation datasets in K562, Jurkat, and RPE1 cells. STRAND improves discrimination scores by up to 33% in low-sample regimes, achieves the best average rank on unseen gene perturbation benchmarks, and improves transfer to novel cell lines by up to 0.14 in Pearson correlation. Ablations isolate the gains to sequence conditioning and transport, and case studies show that STRAND resolves functionally alternative transcription start sites missed by gene-level models.

q-bio.GN↗

arXiv2025

Representation Entanglement for Generation: Training Diffusion Transformers Is Much Easier Than You Think

REPA and its variants effectively mitigate training challenges in diffusion models by incorporating external visual representations from pretrained models, through alignment between the noisy hidden projections of denoising networks and foundational clean image representations. We argue that the external alignment, which is absent during the entire denoising inference process, falls short of fully harnessing the potential of discriminative representations. In this work, we propose a straightforward method called Representation Entanglement for Generation (REG), which entangles low-level image latents with a single high-level class token from pretrained foundation models for denoising. REG acquires the capability to produce coherent image-class pairs directly from pure noise, substantially improving both generation quality and training efficiency. This is accomplished with negligible additional inference overhead, requiring only one single additional token for denoising (<0.5\% increase in FLOPs and latency). The inference process concurrently reconstructs both image latents and their corresponding global semantics, where the acquired semantic knowledge actively guides and enhances the image generation process. On ImageNet 256$\times$256, SiT-XL/2 + REG demonstrates remarkable convergence acceleration, achieving $\textbf{63}\times$ and $\textbf{23}\times$ faster training than SiT-XL/2 and SiT-XL/2 + REPA, respectively. More impressively, SiT-L/2 + REG trained for merely 400K iterations outperforms SiT-XL/2 + REPA trained for 4M iterations ($\textbf{10}\times$ longer). Code is available at: https://github.com/Martinser/REG.

cs.CV↗

arXiv2025

A Generative AI System for Biomedical Data Discovery with Grammar-Based Visualizations

We explore the potential for combining generative AI with grammar-based visualizations for biomedical data discovery. In our prototype, we use a multi-agent system to generate visualization specifications and apply filters. These visualizations are linked together, resulting in an interactive dashboard that is progressively constructed. Our system leverages the strengths of natural language while maintaining the utility of traditional user interfaces. Furthermore, we utilize generated interactive widgets enabling user adjustment. Finally, we demonstrate the potential utility of this system for biomedical data discovery with a case study.

cs.HC↗

arXiv2025

Multimodal Medical Code Tokenizer

Foundation models trained on patient electronic health records (EHRs) require tokenizing medical data into sequences of discrete vocabulary items. Existing tokenizers treat medical codes from EHRs as isolated textual tokens. However, each medical code is defined by its textual description, its position in ontological hierarchies, and its relationships to other codes, such as disease co-occurrences and drug-treatment associations. Medical vocabularies contain more than 600,000 codes with critical information for clinical reasoning. We introduce MedTok, a multimodal medical code tokenizer that uses the text descriptions and relational context of codes. MedTok processes text using a language model encoder and encodes the relational structure with a graph encoder. It then quantizes both modalities into a unified token space, preserving modality-specific and cross-modality information. We integrate MedTok into five EHR models and evaluate it on operational and clinical tasks across in-patient and out-patient datasets, including outcome prediction, diagnosis classification, drug recommendation, and risk stratification. Swapping standard EHR tokenizers with MedTok improves AUPRC across all EHR models, by 4.10% on MIMIC-III, 4.78% on MIMIC-IV, and 11.32% on EHRShot, with the largest gains in drug recommendation. Beyond EHR modeling, we demonstrate using MedTok tokenizer with medical QA systems. Our results demonstrate the potential of MedTok as a unified tokenizer for medical codes, improving tokenization for medical foundation models.

cs.CL↗

arXiv2025

Composable Interventions for Language Models

Test-time interventions for language models can enhance factual accuracy, mitigate harmful outputs, and improve model efficiency without costly retraining. But despite a flood of new methods, different types of interventions are largely developing independently. In practice, multiple interventions must be applied sequentially to the same model, yet we lack standardized ways to study how interventions interact. We fill this gap by introducing composable interventions, a framework to study the effects of using multiple interventions on the same language models, featuring new metrics and a unified codebase. Using our framework, we conduct extensive experiments and compose popular methods from three emerging intervention categories -- Knowledge Editing, Model Compression, and Machine Unlearning. Our results from 310 different compositions uncover meaningful interactions: compression hinders editing and unlearning, composing interventions hinges on their order of application, and popular general-purpose metrics are inadequate for assessing composability. Taken together, our findings showcase clear gaps in composability, suggesting a need for new multi-objective interventions. All of our code is public: https://github.com/hartvigsen-group/composable-interventions.

cs.LG↗

arXiv2025

TxAgent: An AI Agent for Therapeutic Reasoning Across a Universe of Tools

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.

cs.AI↗

arXiv2025

KGARevion: An AI Agent for Knowledge-Intensive Biomedical QA

Biomedical reasoning integrates structured, codified knowledge with tacit, experience-driven insights. Depending on the context, quantity, and nature of available evidence, researchers and clinicians use diverse strategies, including rule-based, prototype-based, and case-based reasoning. Effective medical AI models must handle this complexity while ensuring reliability and adaptability. We introduce KGARevion, a knowledge graph-based agent that answers knowledge-intensive questions. Upon receiving a query, KGARevion generates relevant triplets by leveraging the latent knowledge embedded in a large language model. It then verifies these triplets against a grounded knowledge graph, filtering out errors and retaining only accurate, contextually relevant information for the final answer. This multi-step process strengthens reasoning, adapts to different models of medical inference, and outperforms retrieval-augmented generation-based approaches that lack effective verification mechanisms. Evaluations on medical QA benchmarks show that KGARevion improves accuracy by over 5.2% over 15 models in handling complex medical queries. To further assess its effectiveness, we curated three new medical QA datasets with varying levels of semantic complexity, where KGARevion improved accuracy by 10.4%. The agent integrates with different LLMs and biomedical knowledge graphs for broad applicability across knowledge-intensive tasks. We evaluated KGARevion on AfriMed-QA, a newly introduced dataset focused on African healthcare, demonstrating its strong zero-shot generalization to underrepresented medical contexts.

cs.AI↗

arXiv2025

A Causality-aware Paradigm for Evaluating Creativity of Multimodal Large Language Models

Recently, numerous benchmarks have been developed to evaluate the logical reasoning abilities of large language models (LLMs). However, assessing the equally important creative capabilities of LLMs is challenging due to the subjective, diverse, and data-scarce nature of creativity, especially in multimodal scenarios. In this paper, we consider the comprehensive pipeline for evaluating the creativity of multimodal LLMs, with a focus on suitable evaluation platforms and methodologies. First, we find the Oogiri game, a creativity-driven task requiring humor, associative thinking, and the ability to produce unexpected responses to text, images, or both. This game aligns well with the input-output structure of modern multimodal LLMs and benefits from a rich repository of high-quality, human-annotated creative responses, making it an ideal platform for studying LLM creativity. Next, beyond using the Oogiri game for standard evaluations like ranking and selection, we propose LoTbench, an interactive, causality-aware evaluation framework, to further address some intrinsic risks in standard evaluations, such as information leakage and limited interpretability. The proposed LoTbench not only quantifies LLM creativity more effectively but also visualizes the underlying creative thought processes. Our results show that while most LLMs exhibit constrained creativity, the performance gap between LLMs and humans is not insurmountable. Furthermore, we observe a strong correlation between results from the multimodal cognition benchmark MMMU and LoTbench, but only a weak connection with traditional creativity metrics. This suggests that LoTbench better aligns with human cognitive theories, highlighting cognition as a critical foundation in the early stages of creativity and enabling the bridging of diverse concepts. https://lotbench.github.io

cs.AI↗

arXiv2024

UniTS: A Unified Multi-Task Time Series Model

Although pre-trained transformers and reprogrammed text-based LLMs have shown strong performance on time series tasks, the best-performing architectures vary widely across tasks, with most models narrowly focused on specific areas, such as time series forecasting. Unifying predictive and generative time series tasks within a single model remains challenging. We introduce UniTS, a unified multi-task time series model that utilizes task tokenization to integrate predictive and generative tasks into a single framework. UniTS employs a modified transformer block to capture universal time series representations, enabling transferability from a heterogeneous, multi-domain pre-training dataset-characterized by diverse dynamic patterns, sampling rates, and temporal scales-to a wide range of downstream datasets with varied task specifications and data domains. Tested on 38 datasets across human activity sensors, healthcare, engineering, and finance, UniTS achieves superior performance compared to 12 forecasting models, 20 classification models, 18 anomaly detection models, and 16 imputation models, including adapted text-based LLMs. UniTS also demonstrates strong few-shot and prompt capabilities when applied to new domains and tasks. In single-task settings, UniTS outperforms competitive task-specialized time series models. Code and datasets are available at https://github.com/mims-harvard/UniTS.

cs.LG↗

arXiv2024

MoExtend: Tuning New Experts for Modality and Task Extension

Large language models (LLMs) excel in various tasks but are primarily trained on text data, limiting their application scope. Expanding LLM capabilities to include vision-language understanding is vital, yet training them on multimodal data from scratch is challenging and costly. Existing instruction tuning methods, e.g., LLAVA, often connects a pretrained CLIP vision encoder and LLMs via fully fine-tuning LLMs to bridge the modality gap. However, full fine-tuning is plagued by catastrophic forgetting, i.e., forgetting previous knowledge, and high training costs particularly in the era of increasing tasks and modalities. To solve this issue, we introduce MoExtend, an effective framework designed to streamline the modality adaptation and extension of Mixture-of-Experts (MoE) models. MoExtend seamlessly integrates new experts into pre-trained MoE models, endowing them with novel knowledge without the need to tune pretrained models such as MoE and vision encoders. This approach enables rapid adaptation and extension to new modal data or tasks, effectively addressing the challenge of accommodating new modalities within LLMs. Furthermore, MoExtend avoids tuning pretrained models, thus mitigating the risk of catastrophic forgetting. Experimental results demonstrate the efficacy and efficiency of MoExtend in enhancing the multimodal capabilities of LLMs, contributing to advancements in multimodal AI research. Code: https://github.com/zhongshsh/MoExtend.

cs.CV↗

arXiv2024

Empowering Biomedical Discovery with AI Agents

We envision "AI scientists" as systems capable of skeptical learning and reasoning that empower biomedical research through collaborative agents that integrate AI models and biomedical tools with experimental platforms. Rather than taking humans out of the discovery process, biomedical AI agents combine human creativity and expertise with AI's ability to analyze large datasets, navigate hypothesis spaces, and execute repetitive tasks. AI agents are poised to be proficient in various tasks, planning discovery workflows and performing self-assessment to identify and mitigate gaps in their knowledge. These agents use large language models and generative models to feature structured memory for continual learning and use machine learning tools to incorporate scientific knowledge, biological principles, and theories. AI agents can impact areas ranging from virtual cell simulation, programmable control of phenotypes, and the design of cellular circuits to developing new therapies.

cs.AI↗