Evaluating Agentic Bioinformatics through Function, Evidence, and Validation

Abstract

Large language model agents increasingly plan, execute, and interpret biological analyses, yet fluent responses, successful tool calls, and benchmark performance alone do not establish scientific credibility. Existing reviews primarily organize biological agents by application, architecture, and agentic capability, but do not jointly operationalize the accountability of agent-generated workflows. We address this gap by treating the inspectable workflow trajectory, rather than architecture or final output alone, as the primary unit of analysis. We introduce the Function--Evidence--Validation (FEV) framework, which separates demonstrated workflow operations, traceable support for actions and claims, and use-case-specific validation. Using FEV, we map 109 agentic or agent-adjacent systems and 28 benchmark or evaluation resources, representing 128 unique publications across genomics, single-cell and spatial omics, protein science, drug discovery, computational pathology, and general bioinformatics automation. Across domains, planning and tool-mediated execution have advanced more rapidly than replayability, provenance, robust scientific assessment, external validation, and prospective empirical testing. We therefore argue that agentic bioinformatics should be assessed through workflow correctness rather than final-answer correctness alone. FEV provides a practical basis for comparing systems and designing transparent, auditable, and scientifically accountable bioinformatics workflows.