Shanghua Gao

Shanshan Zhong, Shanghua Gao, Zhongzhan Huang et al.

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.

Arinbjorn Kolbeinsson, Kyle O'Brien, Tianjin Huang et al.

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.

Shanghua Gao, Teddy Koker, Owen Queen et al.

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.

Shanghua Gao, Ada Fang, Marinka Zitnik

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).

Shanghua Gao, Richard Zhu, Pengwei Sui et al.

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. In genomics, unified ecosystems have transformed research by enabling interoperability, reuse, and community-driven development; AI scientists require comparable infrastructure. We present ToolUniverse, an ecosystem 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 by providing more than 600 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 a case study of hypercholesterolemia, ToolUniverse was used to create an AI scientist to identify a potent analog of a drug with favorable predicted properties. The open-source ToolUniverse is available at https://aiscientist.tools.

Shanghua Gao, Ada Fang, Yepeng Huang et al.

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.

Shanshan Zhong, Zhongzhan Huang, Shanghua Gao et al.

Chain-of-Thought (CoT) guides large language models (LLMs) to reason step-by-step, and can motivate their logical reasoning ability. While effective for logical tasks, CoT is not conducive to creative problem-solving which often requires out-of-box thoughts and is crucial for innovation advancements. In this paper, we explore the Leap-of-Thought (LoT) abilities within LLMs -- a non-sequential, creative paradigm involving strong associations and knowledge leaps. To this end, we study LLMs on the popular Oogiri game which needs participants to have good creativity and strong associative thinking for responding unexpectedly and humorously to the given image, text, or both, and thus is suitable for LoT study. Then to investigate LLMs' LoT ability in the Oogiri game, we first build a multimodal and multilingual Oogiri-GO dataset which contains over 130,000 samples from the Oogiri game, and observe the insufficient LoT ability or failures of most existing LLMs on the Oogiri game. Accordingly, we introduce a creative Leap-of-Thought (CLoT) paradigm to improve LLM's LoT ability. CLoT first formulates the Oogiri-GO dataset into LoT-oriented instruction tuning data to train pretrained LLM for achieving certain LoT humor generation and discrimination abilities. Then CLoT designs an explorative self-refinement that encourages the LLM to generate more creative LoT data via exploring parallels between seemingly unrelated concepts and selects high-quality data to train itself for self-refinement. CLoT not only excels in humor generation in the Oogiri game but also boosts creative abilities in various tasks like cloud guessing game and divergent association task. These findings advance our understanding and offer a pathway to improve LLMs' creative capacities for innovative applications across domains. The dataset, code, and models will be released online. https://zhongshsh.github.io/CLoT/.

Shanghua Gao, Richard Zhu, Zhenglun Kong et al.

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.

Zhongzhan Huang, Shanshan Zhong, Pan Zhou et al.

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

Xiaorui Su, Shvat Messica, Yepeng Huang et al.

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.

Boyang Fu, George Dasoulas, Sameer Gabbita et al.

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.

Devin Lange, Shanghua Gao, Pengwei Sui et al.

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, even in the new world of generative AI. In our prototype system, YAC, Yet Another Chatbot, we bridge the gap between natural language and interactive visualizations by generating structured declarative output with a multi-agent system and interpreting that output to render linked interactive visualizations and apply data filters. Furthermore, we include widgets, which allow users to adjust the values of that structured output through user interface elements. We reflect on the capabilities and design of this system with an analysis of its technical dimensions and illustrate the capabilities through four usage scenarios.

Devin Lange, Shanghua Gao, Pengwei Sui et al.

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.