Zane Koch, Asmamaw T. Wassie, Javier Valdes-Aleman +5cs.AI q-bio.QM
Artificial intelligence (AI) promises to accelerate biological research by automating computational analyses. Yet the ability of AI agents to carry out computational biology at the scale of complete research studies has not been systematically evaluated. Here we introduce BixBench3, a benchmark that measures the capacity of AI agents to process raw biological data through to scientific results. We designed BixBench3 tasks to mirror the delegation of work from a scientist to an agent: the scientist chooses the research question and high-level methods, then delegates implementation of all analyses to the agent. In each task, an agent receives a research objective, methodological guidance, and raw data derived from a published scientific study, and must execute a sequence of analyses to achieve the research objective. The data artifacts resulting from these analyses - such as peak call matrices or differential expression tables - are programmatically graded against the corresponding artifacts generated and reported in the original study. Across 20 BixBench3 tasks encompassing the generation of 138 unique artifacts, we find that 13 frontier models achieve scores ranging from 0.00 for Gemini 3.1 Flash Lite to 0.48 for GPT 5.6 Sol. Agents perform worse on tasks with larger raw datasets (0.36 on tasks with <100 GB versus 0.10 on tasks with >100 GB) and on analyses requiring more sequential steps (0.36 at 1-2 steps vs 0.24 at 3+). On average, agents use 6.8 hours, 102 million tokens, and $43 to complete each task, with the longest attempts consuming 24 hours, 1.07 billion tokens, and $525. Notably, the highest-scoring agents used fewer tokens and were cheaper than less performant options. These results reveal that LLMs vary substantially in their ability to (1) execute multiple sequential analysis steps coherently, (2) manage large quantities of raw data, and (3) work across scientific domains.
High-performance computing (HPC) clusters remain the backbone of large-scale scientific computation, traditionally executing deterministic, linear pipelines optimised for predictable performance. However, the pervasive integration of artificial intelligence (AI) and foundation models into scientific research has introduced a fundamentally new computational paradigm. AI-driven workflows are characteristically iterative, data-driven, and probabilistic, introducing unique challenges regarding data gravity, heterogeneous resource management, and complex workflow orchestration. This guide provides twelve practical tips designed to help researchers design efficient, scalable, and reproducible AI-driven HPC workflows. By addressing critical system-level bottlenecks - such as containerisation for environment portability, strategic deployment of job arrays, explicit feedback loop mechanics, and I/O optimisation for small files - this article offers a framework for transitioning from rigid execution pipelines to adaptive, intelligent computational environments. While these architectural principles are broadly applicable across distributed environments, they are particularly tailored to the resource-intensive throughput demands of modern computational biology.