Sarah Martinson, Michael P. Brenner, Martyna Plomecka, Brian P. Williams, Nicholas G. Reich, Zahra Shamsi
Probabilistic forecasting of infectious diseases is crucial for public health monitoring and preparedness but has historically relied on labor-intensive manual model curation by expert modeling teams. Bespoke development is an obstacle to scaling models to granular geographic resolutions or emerging pathogens. Here, we prospectively evaluate Empirical Research Assistance (ERA), an autonomous system that uses Large Language Model-guided tree search to iteratively generate, evaluate, and optimize executable forecasting software. ERA was primarily prompted with methodological approaches to implement, while in some instances it was tasked with developing forecasting approaches from scratch. In a fully prospective, real-time evaluation during the 2025-26 United States respiratory season, ERA generated methodologically diverse models for influenza, COVID-19, and respiratory syncytial virus (RSV). Aggregating a selection of these automatically-generated models yielded an ensemble that ranked first overall in official Centers for Disease Control and Prevention (CDC) post-season evaluations and outperformed the gold-standard CDC forecast ensembles across all three pathogens in a real-time prediction challenge. Additionally, ERA successfully navigated data-scarce scenarios for RSV. Controlled retrospective ablations allowed for additional explorations of the impact of optimization target and instruction-following on forecast accuracy. Preliminary experiments indicate that ERA's search optimization metric influences behavior of output forecasts, and using higher-tier language models in-search improves predictive performance. By autonomously generating interpretable code that creates epidemiologically relevant predictions, this framework provides a path toward rapidly scaling high-quality disease forecasting.
Eser Aygün, Anastasiya Belyaeva, Gheorghe Comanici, Marc Coram, Hao Cui, Jake Garrison, Renee Johnston Anton Kast, Cory Y. McLean 等 42 位作者
The cycle of scientific discovery is frequently bottlenecked by the slow, manual creation of software to support computational experiments\cite{hannay2009how}. To address this, we present Empirical Research Assistance (ERA), an AI system that creates expert-level scientific software whose goal is to maximize a quality metric. The system uses a Large Language Model (LLM) and Tree Search (TS)\cite{silver2016mastering} to systematically improve the quality metric and intelligently navigate the large space of possible solutions. ERA achieves expert-level results when it explores and integrates complex research ideas from external sources. The effectiveness of tree search is demonstrated across a diverse range of tasks. In bioinformatics, ERA discovered 40 novel methods for single-cell data analysis that outperformed the top human-developed methods on a public leaderboard. In epidemiology, ERA generated 14 models that outperformed the CDC ensemble and all other individual models for forecasting COVID-19 hospitalizations. ERA also produced expert-level software for geospatial analysis, neural activity prediction in zebrafish, and numerical solution of integrals, and a novel rule-based construction for time series forecasting. By devising and implementing novel solutions to diverse tasks, ERA represents a significant step towards accelerating scientific progress.
We present a case study for how AI coding systems can be used to generate novel scientific hypotheses. We combine a generic coding agent (Google's AntiGravity) with an LLM-driven tree search algorithm (Empirical Research Assistance / ERA) to autonomously generate high-efficiency three-dimensional photovoltaic (3DPV) structures that overcome losses limiting flat solar panels at mid-latitudes. These structures operate by presenting favorable angles to the sun throughout the day, and for illustrative purposes we focus on optimizing performance for a single solar day. Our workflow begins by using AntiGravity to reproduce calculations \cite{bernardi2012solar} showing that 3DPV can have energy densities much higher than stationary flat PV panels. We use these initial designs as the starting point for large scale tree search, where we seek improved solutions and score them for their diurnal yield. The initial tree search leads to nominally more efficient solutions, yet they are caused by algorithmic reward hacking, arising from non-physical design features such as structurally levitating disconnected tiers and exploitations of the discretizations in the optics solver. To counteract this, we develop a workflow where the coding agent iteratively patches the physics engine with constraints to eliminate reward hacking. With reward-hacking eliminated, ERA discovers a series of designs with various constraints and improved performance, including optimal designs with different fixed collector areas, optimizing zenith tracking and avoiding self shadowing. Combining coding agents with tree search (ERA) provides a powerful platform for scientific discovery, for problems whose solutions can be empirically evaluated with a score function.
David P. Woodruff, Vincent Cohen-Addad, Lalit Jain, Jieming Mao, Song Zuo, MohammadHossein Bateni, Simina Branzei, Michael P. Brenner 等 36 位作者
Recent advances in large language models (LLMs) have opened new avenues for accelerating scientific research. While models are increasingly capable of assisting with routine tasks, their ability to contribute to novel, expert-level mathematical discovery is less understood. We present a collection of case studies demonstrating how researchers have successfully collaborated with advanced AI models, specifically Google's Gemini-based models (in particular Gemini Deep Think and its advanced variants), to solve open problems, refute conjectures, and generate new proofs across diverse areas in theoretical computer science, as well as other areas such as economics, optimization, and physics. Based on these experiences, we extract common techniques for effective human-AI collaboration in theoretical research, such as iterative refinement, problem decomposition, and cross-disciplinary knowledge transfer. While the majority of our results stem from this interactive, conversational methodology, we also highlight specific instances that push beyond standard chat interfaces. These include deploying the model as a rigorous adversarial reviewer to detect subtle flaws in existing proofs, and embedding it within a "neuro-symbolic" loop that autonomously writes and executes code to verify complex derivations. Together, these examples highlight the potential of AI not just as a tool for automation, but as a versatile, genuine partner in the creative process of scientific discovery.
Michael P. Brenner, Vincent Cohen-Addad, David Woodruff
This paper demonstrates that artificial intelligence can accelerate mathematical discovery by autonomously solving an open problem in theoretical physics. We present a neuro-symbolic system, combining the Gemini Deep Think large language model with a systematic Tree Search (TS) framework and automated numerical feedback, that successfully derived novel, exact analytical solutions for the power spectrum of gravitational radiation emitted by cosmic strings. Specifically, the agent evaluated the core integral $I(N,α)$ for arbitrary loop geometries, directly improving upon recent AI-assisted attempts \cite{BCE+25} that only yielded partial asymptotic solutions. To substantiate our methodological claims regarding AI-accelerated discovery and to ensure transparency, we detail system prompts, search constraints, and intermittent feedback loops that guided the model. The agent identified a suite of 6 different analytical methods, the most elegant of which expands the kernel in Gegenbauer polynomials $C_l^{(3/2)}$ to naturally absorb the integrand's singularities. The methods lead to an asymptotic result for $I(N,α)$ at large $N$ that both agrees with numerical results and also connects to the continuous Feynman parameterization of Quantum Field Theory. We detail both the algorithmic methodology that enabled this discovery and the resulting mathematical derivations.