OmicOS: A Comprehensive Omics Ecosystem Infrastructure and Agent System for the AI Era

Abstract Biology has accumulated a vast ecosystem of omics methods, but much of this ecosystem remains built for expert humans rather than scientific agents. Methods are scattered across Python packages, R/Bioconductor and CRAN workflows, command-line tools, incompatible data containers and implicit object states, making even routine analyses difficult for an AI system to choose, execute and verify reliably. Here we introduce OmicOS, a comprehensive omics ecosystem infrastructure and agent system that turns OmicVerse V2, an open-source omics community, into an executable foundation for agentic biology. OmicVerse V2 provides the community substrate: scalable AnnDataOOM-compatible rust backends, agent-friendly Python algorithms for single-cell, spatial, bulk and multi-omics analysis, interfaces to single-cell foundation models, and Python-native reconstructions of historically R-centred Bioconductor/CRAN-style workflows. OmicOS makes this substrate actionable by registering analytical functions as state-aware capability contracts, allowing agents to inspect live data objects, select valid methods, execute controlled workflows and record provenance. The result is not a fixed pipeline, but a programmable omics environment in which agents compose real analyses from verified community methods rather than inventing tools. Across external and purpose-built benchmarks, OmicOS ranked first among the evaluated systems, reaching 81.2% on BiomniBench. Adding OmicVerse to a minimal agent improved task completion by up to 34.2 percentage points with qwen-3.6-35b, and controlled ablations showed that the gains came from registry-grounded execution rather than from larger models, documentation retrieval or unrestricted tool exposure. The same infrastructure scaled to atlas-sized data, reproduced R-centred workflows in Python and converted external pathology software into agent-usable skills. In a discovery task starting from a whole-body spatial map and the term “Alzheimer’s disease”, OmicOS composed a non-canonical workflow that integrated spatial expression, genetic association, eQTL and colocalization evidence to nominate a colon epithelial risk axis centred on PICALM, CD2AP and CR1. Together, OmicVerse and OmicOS define an open foundation for AI-era omics, showing how a community of biological methods can be transformed into a reliable, extensible and agent-operable system for discovery. Highlight OmicVerse 2.0 consolidates 694 methods spanning 11 omics domains into agent-callable high-level APIs. RebuildR automatically reconstructs and evolves R/Bioconductor methods as Python-native implementations under output-equivalence gates. OmicOS establishes a state-of-the-art omics agent harness, ranking first on general omics benchmarks across models and substantially improving the analytical capability of local open-source models. Compositional use of ecosystem modules nominates a colon epithelial axis associated with Alzheimer’s disease risk. External algorithm packages supporting automatic iterative evolution can be integrated into the OmicOS ecosystem.