Yikun Zhang, Xiwei Cheng, Mingze Yuan, Yu Zhang, Brian Shim, Aarti Krishnan, Daniel Rosen, Kunyang Sun 等 18 位作者
Molecular discovery requires navigating vast combinatorial search spaces while balancing competing biological objectives. AI agents can automate expert-defined molecular design protocols, but automation alone does not address how to optimize workflows for new tasks or improve their development through experience. Here we introduce MoLRSI, an AI agent that combines systematic optimization of workflows and model architectures with persistent cross-task memory to recursively improve its search policy for molecular discovery. Workflow performance, refinement outcomes, and execution feedback guide subsequent searches, allowing the agent to improve both its workflows and its strategy for developing them. We evaluate MoLRSI in two challenging molecular discovery settings that require balancing competing properties. In antibiotic discovery, MoLRSI developed a screening workflow balancing antibacterial activity, cytotoxicity and structural novelty, achieving an experimental hit rate of 15.9%, compared with 8.7% for a previous expert-led workflow using the same training data and screening library. In de novo peptide-MHC binder design, MoLRSI developed workflows that jointly consider target binding and specificity, producing eight experimentally validated hits against MART-1 and SARS-CoV-1 pMHCs with preferential binding over tested off-targets while Claude Science completely failed. These findings demonstrate how experience-guided workflow optimization can address competing discovery objectives while improving the search strategies used in subsequent campaigns.
Laura Laurenti, David Liu, Brian Kulis, Men-Andrin Meier, Christopher Johnson
Earthquake sequences are stochastic on two separated timescales: the seismic waves of any individual earthquake propagate over seconds to minutes, while the earthquakes themselves arrive as a sparse, self-exciting occurrence process, with inter-event intervals from seconds to months. Respecting both scales in one training objective is the open challenge. Foundation models (FMs) for seismic waveforms instead import their learning targets from audio and vision, where every target is computed from a single fixed-length window. Such a window holds one realization of the wave propagation (an earthquake trace), never the occurrence process that decides when earthquakes happen. We develop nine model designs sharing one Mamba encoder-decoder, trained on a fixed corpus of 3M windows, varying the self-supervised objective, quantization bottleneck and mixer; the two key comparisons are architecture-matched, varying the objective alone. Each checkpoint is evaluated frozen on three downstream tasks. Varying the target redistributes downstream skill rather than raising it, and no checkpoint wins everywhere. Adding masking pressure to our strongest classifier re-specializes it rather than making it a generalist: it gains 6.9 points of few-shot P-wave picking precision and loses 9.6 points of few-shot classification accuracy. By the standard imported from language and vision, these models are feature extractors rather than FMs. Controls on capacity, architecture, and domain proximity do not explain why skill moves rather than rises. Against task-specific baselines the advantage is regime-dependent: our checkpoints beat them few-shot on classification and ground-motion prediction, and trail them on full data. We argue the binding constraint is the target, and that settling the question requires a learning target defined across events, the timescale that makes seismicity stochastic in the first place.