Plato-Bio: verification-first biological novelty screening with temporal rediscovery and structural benchmarks

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.

While recent advances in large language models have enabled end-to-end automated manuscript generation, existing systems suffer from three critical deficiencies: (i) generated claims are not deterministically grounded in verifiable literature, (ii) experimental results are frequently fabricated rather than executed, and (iii) there exists no standardized, multi-dimensional framework to assess whether AI-generated manuscripts meet the quality and rigor required for real-world publication. We present Prompt-to-Paper, a multi-agent framework that directly addresses this evaluation gap through three integrated innovations. First, a deterministic retrieval-augmented generation pipeline with section-aware relevance scoring and snowball citation expansion grounds every claim in a verifiable corpus of 60--100 papers. Second, an autonomous coding agent executes real computational biology experiments replacing synthetic outputs with genuine numerical results. Third, an eight-dimensional automated quality scorer, benchmarked with approximate reference statistics from published papers and augmented with explicit hallucination penalties, provides standardized, reproducible quality assessments. The quality-driven improvement loop uses a context-rich reviser that routes each iteration to one of three researcher actions and fires a deep research cycle every ten iterations to re-run experiments and re-manuscript from stronger outputs. We validate the system on five bioinformatics case studies; all five cases compiled submission-formatted PDFs with zero out-of-range citations. The improvement loop raises manuscript quality by an average of +17.96 points on a 0--100 scale (maximum +26.04. As partial external checks, a human reviewer scored the five manuscripts at an average of 7.0 out of 10. Complete manuscripts are produced at approximately 0.31 USD per paper.

A working citation looks like proof -- but the fact that a link resolves does not mean the cited paper supports the claim. I find that current agentic models rarely fabricate citations (over $99\%$ resolve), yet roughly $15.9\%$ link to the wrong paper. Existing benchmarks miss this failure mode: when a question has a fixed answer key, a model can reproduce the expected source from that key rather than independently verifying that the source supports the claim. I introduce \textbf{\openbiorq{}}, a retrieval-grounded agentic benchmark of $12{,}553$ unsolved biomedical research questions across $12$ domains that treats open questions as a faithfulness-and-abstention probe. To my knowledge, this is the first biomedical benchmark to combine an agentic setting -- where the model must issue multiple tool calls -- with unsolved questions that have no answer key. Openness is verified against real follow-up evidence rather than a model's parametric knowledge. Difficulty is empirical: I anchor it on questions that three open-weight reference models fail to answer, rather than on subjective hardness labels. On this hardest subset, held-out models from the same lineage as the difficulty anchors solve only ~17%, while three independent frontier agents (Gemini-3-Pro, Opus-4.7, GPT-5.5) span a wide 29-60% range. The benchmark is thus hard, non-saturating (the best agent still leaves ~33-40% unsolved), and discriminating across capability tiers. Beyond difficulty, I observe agentic collapse on the hardest questions, where agents stop using their tools. For the most collapse-prone model, blocking tool access entirely barely changes its score -- so tools stop paying off exactly where they are needed most. A frozen per-question checklist raises inter-judge agreement from Spearman 0.35 to 0.82.