Xihong Lin

Xiangru Tang, Zhuoyun Yu, Jiapeng Chen et al.

Virtual cell modeling represents an emerging frontier at the intersection of artificial intelligence and biology, aiming to predict quantities such as responses to diverse perturbations quantitatively. However, autonomously building computational models for virtual cells is challenging due to the complexity of biological systems, the heterogeneity of data modalities, and the need for domain-specific expertise across multiple disciplines. Here, we introduce CellForge, an agentic system that leverages a multi-agent framework that transforms presented biological datasets and research objectives directly into optimized computational models for virtual cells. More specifically, given only raw single-cell multi-omics data and task descriptions as input, CellForge outputs both an optimized model architecture and executable code for training virtual cell models and inference. The framework integrates three core modules: Task Analysis for presented dataset characterization and relevant literature retrieval, Method Design, where specialized agents collaboratively develop optimized modeling strategies, and Experiment Execution for automated generation of code. The agents in the Design module are separated into experts with differing perspectives and a central moderator, and have to collaboratively exchange solutions until they achieve a reasonable consensus. We demonstrate CellForge's capabilities in single-cell perturbation prediction, using six diverse datasets that encompass gene knockouts, drug treatments, and cytokine stimulations across multiple modalities. CellForge consistently outperforms task-specific state-of-the-art methods. Overall, CellForge demonstrates how iterative interaction between LLM agents with differing perspectives provides better solutions than directly addressing a modeling challenge. Our code is publicly available at https://github.com/gersteinlab/CellForge.

Hongru Du, Jianan Zhao, Yang Zhao et al.

Forecasting the short-term spread of an ongoing disease outbreak is a formidable challenge due to the complexity of contributing factors, some of which can be characterized through interlinked, multi-modality variables such as epidemiological time series data, viral biology, population demographics, and the intersection of public policy and human behavior. Existing forecasting model frameworks struggle with the multifaceted nature of relevant data and robust results translation, which hinders their performances and the provision of actionable insights for public health decision-makers. Our work introduces PandemicLLM, a novel framework with multi-modal Large Language Models (LLMs) that reformulates real-time forecasting of disease spread as a text reasoning problem, with the ability to incorporate real-time, complex, non-numerical information that previously unattainable in traditional forecasting models. This approach, through a unique AI-human cooperative prompt design and time series representation learning, encodes multi-modal data for LLMs. The model is applied to the COVID-19 pandemic, and trained to utilize textual public health policies, genomic surveillance, spatial, and epidemiological time series data, and is subsequently tested across all 50 states of the U.S. Empirically, PandemicLLM is shown to be a high-performing pandemic forecasting framework that effectively captures the impact of emerging variants and can provide timely and accurate predictions. The proposed PandemicLLM opens avenues for incorporating various pandemic-related data in heterogeneous formats and exhibits performance benefits over existing models. This study illuminates the potential of adapting LLMs and representation learning to enhance pandemic forecasting, illustrating how AI innovations can strengthen pandemic responses and crisis management in the future.