Towards Autonomous Mechanistic Reasoning in Virtual Cells

TL;DR

This paper introduces a structured formalism and a multi-agent framework for autonomous mechanistic reasoning in virtual cells, enhancing biological explanation accuracy and supporting scientific discovery.

Contribution

It presents VCR-Agent, a novel multi-agent system that generates and verifies mechanistic explanations, and releases the VC-TRACES dataset for virtual cell reasoning.

Findings

Training with verified explanations improves gene expression prediction.

The framework enhances factual precision in biological reasoning.

The VC-TRACES dataset provides verified mechanistic explanations.

Abstract

Large language models (LLMs) have recently gained significant attention as a promising approach to accelerate scientific discovery. However, their application in open-ended scientific domains such as biology remains limited, primarily due to the lack of factually grounded and actionable explanations. To address this, we introduce a structured explanation formalism for virtual cells that represents biological reasoning as mechanistic action graphs, enabling systematic verification and falsification. Building upon this, we propose VCR-Agent, a multi-agent framework that integrates biologically grounded knowledge retrieval with a verifier-based filtering approach to generate and validate mechanistic reasoning autonomously. Using this framework, we release VC-TRACES dataset, which consists of verified mechanistic explanations derived from the Tahoe-100M atlas. Empirically, we demonstrate that training with these explanations improves factual precision and provides a more effective supervision signal for downstream gene expression prediction. These results underscore the importance of reliable mechanistic reasoning for virtual cells, achieved through the synergy of multi-agent and rigorous verification.