A Self-Evolving Agentic System for Automated Generation and Execution of Biological Protocols

Autonomous wet-lab experimentation requires more than plausible protocol text: biological intent, quantitative procedures, device constraints and experimental feedback must remain aligned from protocol and SOP design to code and physical execution. We developed ProtoPilot, a self-evolving multi-agent system, together with an expert-grounded benchmark and evaluation framework for testing this conversion as an experimental automation problem. The framework spans 294 synthetic-biology and molecular-biology tasks derived from 98 gold-standard protocols, wet-lab expert rubrics, device-level validity gates and real experimental tests. ProtoPilot incorporates layer-wise verifiability, multi-agent orchestration and a runtime-updated skill library to generate protocols, expand SOPs, synthesize SDK-compliant code and revise workflows from wet-lab feedback. It achieved a Top@3 expert-preference rate of 90.2%, an overall protocol-to-code gate pass rate of 89.5% and an Opentrons pass rate of 88.24%, compared with 32.35% for OpenTrons-AI. Wet-lab validation produced interpretable readouts, Sanger-confirmed products and feedback-corrected PCA-assembled DNA targets, establishing a verifiable route to autonomous experimentation. Together, these results show that the evaluation framework captures execution-relevant requirements for autonomous wet-lab automation, and that ProtoPilot can meet them by converting protocol and code generation into validated execution and feedback-guided revision.

Multimodal Mixture-of-Experts with Retrieval Augmentation for Protein Active Site Identification

Accurate identification of protein active sites at the residue level is crucial for understanding protein function and advancing drug discovery. However, current methods face two critical challenges: vulnerability in single-instance prediction due to sparse training data, and inadequate modality reliability estimation that leads to performance degradation when unreliable modalities dominate fusion processes. To address these challenges, we introduce Multimodal Mixture-of-Experts with Retrieval Augmentation (MERA), the first retrieval-augmented framework for protein active site identification. MERA employs hierarchical multi-expert retrieval that dynamically aggregates contextual information from chain, sequence, and active-site perspectives through residue-level mixture-of-experts gating. To prevent modality degradation, we propose a reliability-aware fusion strategy based on Dempster-Shafer evidence theory that quantifies modality trustworthiness through belief mass functions and learnable discounting coefficients, enabling principled multimodal integration. Extensive experiments on ProTAD-Gen and TS125 datasets demonstrate that MERA achieves state-of-the-art performance, with 90% AUPRC on active site prediction and significant gains on peptide-binding site identification, validating the effectiveness of retrieval-augmented multi-expert modeling and reliability-guided fusion.