CARIBOU: Computational AI Research Interface for Bioinformatics, Omics, and Unifying Agents

The growing gap between biological data generation and the availability of expert analysts motivates the development of AI systems capable of autonomously performing meaningful computational biology workflows. Here, we present CARIBOU (Computational AI Research Interface for Bioinformatics, Omics, and Unifying Agents), a multi-agent framework designed for practical deployment within institutional research computing environments. CARIBOU organizes specialized AI agents through researcher-modifiable blueprints that encode analytical roles, domain knowledge, and workflow guidance. All analyses are executed within reproducible computational environments compatible with Singularity/Apptainer-based high-performance computing (HPC) systems commonly used in academic research, while maintaining a persistent shared analytical state across multiple stages of analysis. This design enables CARIBOU to iteratively execute, troubleshoot, and refine bioinformatics workflows rather than simply generate static code. We evaluate CARIBOU across unit-task benchmarks, a metadata reconstruction challenge spanning six public datasets, and two end-to-end single-cell RNA-seq analyses using Allen Brain Atlas hippocampus and Tabula Sapiens large intestine datasets, alongside qualitative case studies demonstrating adaptive reasoning during analysis execution. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=137 SRC="FIGDIR/small/727730v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@1028f08org.highwire.dtl.DTLVardef@fc975dorg.highwire.dtl.DTLVardef@1355b2corg.highwire.dtl.DTLVardef@1f4ca39_HPS_FORMAT_FIGEXP M_FIG C_FIG IN BRIEFModern single-cell and spatial omics studies generate datasets that are increasingly difficult to analyze manually, creating a growing bottleneck between data generation and biological discovery. CARIBOU is a multi-agent AI system designed to autonomously perform bioinformatics analyses within the high-performance computing environments used by research institutions. By combining specialized AI agents with persistent execution environments and built-in analytical workflows, CARIBOU can adaptively execute, troubleshoot, and document complex analyses while maintaining reproducibility and compatibility with real-world research infrastructure.