Submitted:
09 June 2026
Posted:
10 June 2026
You are already at the latest version
Abstract
Keywords:
Introduction
1. The Trade-Off Frontier in Plant Genomics
1.1. Three Operational Dimensions of the Frontier
1.2. Why the Constraint Persists
1.3. What Would Count as a Shift
2. A Capability Hierarchy for Autonomous Agents in Plant Genomics
2.1. Levels Defined by Scientific Work
2.2. L1: Knowledge Integration
2.3. L2: Tool Orchestration
2.4. L3: Closed-Loop Computational Discovery
2.5. L4: Self-Evolving Systems
3. Technical Substrate for Auditable Agentic Workflows
3.1. From Plant-Science Pain Points to Agent Paradigms
3.2. From Tool Use to Auditable Execution
3.3. Scope and Limits of Cross-Domain Evidence
3.4. Reliability and Boundary Conditions
3.5. From Case Studies to Benchmarks
| Task Family (Target Level) | Inputs/Scenario | Outputs | Baseline | Stressors | Metrics |
| Literature-based gene prioritisation (L1) | Candidate-gene list, fixed literature/database snapshot, identifier metadata (e.g., rice drought tolerance) | Ranked genes with evidence summaries and citations | Expert consensus, known validated genes | Synonyms, orthology ambiguity, contradictory evidence, outdated annotations | Recall@5/10; MAP; citation precision; provenance completeness; unsupported-claim rate |
| Statistical-genomics workflow execution (L2) | Genotype matrix, phenotype table, genome annotation, expected formats (e.g., maize GWAS follow-up) | QC summary; Manhattan/QQ plots; significant SNPs; effect sizes; logs | Expert-curated reference workflow; WMS-only; published outputs | Missing metadata, genome-build mismatch, file-format variation, parameter ambiguity | Automated steps; reproducibility; effect-size correlation; SNP-list agreement; intervention count |
| Iterative computational hypothesis refinement (L3) | Initial association signals, multi-omics + causal evidence, stopping rules (crop-trait refinement) | Final ranked genes; evidence trail; iteration log with decision trace | Expert panel with disagreement recorded; validated functional evidence where available | Conflicting mutant data, paralogy, tissue-specific expression, partial evidence | Autonomous cycles; evidence-type coverage; NDCG@10; runtime per cycle; intervention count |
4. Challenges, Roadmap, and Call to Action
4.1. Challenges to Deployment
4.2. A Staged Roadmap
4.3. Cost, Privacy, and Local Deployment
4.4. Immediate Priorities and Unresolved Questions
Conclusions
Supplementary Materials
Author Contributions
Acknowledgments
Conflicts of Interest
References
- Acharjee Dip, S.; Li, S.; Zhang, L. PlantMarkerBench: A Multi-Species Benchmark for Evidence-Grounded Plant Marker Reasoning. arXiv 2026, arXiv:2605.10032. [Google Scholar]
- Alam, K.; Roy, B. From Prompt to Pipeline: Large Language Models for Scientific Workflow Development in Bioinformatics. arXiv 2025, arXiv:2507.20122. [Google Scholar] [CrossRef]
- Alber, S.; Chen, B.; Sun, E.; Isakova, A.; Wilk, A.J.; Zou, J. CellVoyager: AI CompBio agent generates new insights by autonomously analyzing biological data. Nat. Methods 2026, 23, 749–759. [Google Scholar] [CrossRef] [PubMed]
- Asai, A.; He, J.; Shao, R.; Shi, W.; Singh, A.; Chang, J.C.; Lo, K.; Soldaini, L.; Feldman, S.; D’Arcy, M.; et al. Synthesizing scientific literature with retrieval-augmented language models. Nature 2026, 650, 857–863. [Google Scholar] [CrossRef]
- Bao, Z.; Liu, Q.; Guo, Y.; Ye, Z.; Shen, J.; Xie, S.; Peng, J.; Huang, X.; Wei, Z. PIORS: Personalized Intelligent Outpatient Reception based on Large Language Model with Multi-Agents Medical Scenario Simulation. arXiv 2024, arXiv:2411.13902. [Google Scholar] [CrossRef]
- Berger, B.; Yu, Y.W. Navigating bottlenecks and trade-offs in genomic data analysis. Nat. Rev. Genet. 2023, 24, 235–250. [Google Scholar] [CrossRef]
- Boiko, D.A.; MacKnight, R.; Kline, B.; Gomes, G. Autonomous chemical research with large language models. Nature 2023, 624, 570–578. [Google Scholar] [CrossRef]
- Bu, D.; Sun, J.; Li, K.; He, Z.; Huang, W.; Hu, J.; Zhang, S.; Lei, S.; Huo, P.; Wang, Z.; et al. Empowering AI data scientists using a multi-agent LLM framework with self-evolving capabilities for autonomous, tool-aware biomedical data analyses. Nat. Biomed. Eng. 2026. [Google Scholar] [CrossRef]
- Chelli, M.; Descamps, J.; Lavoué, V.; Trojani, C.; Azar, M.; Deckert, M.; Raynier, J.-L.; Clowez, G.; Boileau, P.; Ruetsch-Chelli, C. Hallucination Rates and Reference Accuracy of ChatGPT and Bard for Systematic Reviews: Comparative Analysis. J. Med. Internet Res. 2024, 26, e53164. [Google Scholar] [CrossRef]
- Chen, F.; Stogiannidis, I.; Wood, A.; Bueno, D.; Williams, D.; Macfarlane, F.; Grieve, B.D.; Wells, D.; Atkinson, J.A.; Hawkesford, M.J.; et al. A conversational multi-agent AI system for automated plant phenotyping. Nat. Commun. 2026. [Google Scholar] [CrossRef] [PubMed]
- Community, T.G. The Galaxy platform for accessible, reproducible, and collaborative data analyses: 2024 update. Nucleic Acids Res. 2024, 52, W83–W94. [Google Scholar] [CrossRef]
- Devam, M.; Atharva, I. SeqMate: A Novel Large Language Model Pipeline for Automating RNA Sequencing. arXiv 2024. [Google Scholar] [CrossRef]
- Ding, K.; Yu, J.; Huang, J.; Yang, Y.; Zhang, Q.; Chen, H. SciToolAgent: A knowledge-graph-driven scientific agent for multitool integration. Nat. Comput. Sci. 2025, 5, 962–972. [Google Scholar] [CrossRef]
- Dionizije, F.; Marko, Č.; Bruno, P.; Mateo, Č. BioAgent Bench: An AI Agent Evaluation Suite for Bioinformatics. arXiv 2026. [Google Scholar] [CrossRef]
- Dip, S.A.; Mallick, D.; Shuvo, U.A.; Soumma, S.B.; Rafsani, F.; Paul, B.K.; Moumi, N.A.; Ahmed, S.; Zhang, L. Large language model agents for biological intelligence across genomics, proteomics, spatial biology, and biomedicine. Brief. Bioinform. 2026, 27, bbag110. [Google Scholar] [CrossRef]
- Dominguez Del Angel, V.; Hjerde, E.; Sterck, L.; Capella-Gutierrez, S.; Notredame, C.; Vinnere Pettersson, O.; Amselem, J.; Bouri, L.; Bocs, S.; Klopp, C.; et al. Ten steps to get started in Genome Assembly and Annotation. F1000Research 2018, 7. [Google Scholar] [CrossRef] [PubMed]
- Ewels, P.A.; Peltzer, A.; Fillinger, S.; Patel, H.; Alneberg, J.; Wilm, A.; Garcia, M.U.; Di Tommaso, P.; Nahnsen, S. The nf-core framework for community-curated bioinformatics pipelines. Nat. Biotechnol. 2020, 38, 276–278. [Google Scholar] [CrossRef]
- Gabaldón, T.; Koonin, E.V. Functional and evolutionary implications of gene orthology. Nat. Rev. Genet. 2013, 14, 360–366. [Google Scholar] [CrossRef]
- Gao, B.; Huang, Y.; Liu, Y.; Xie, W.; Ma, W.-Y.; Zhang, Y.-Q.; Lan, Y. PharmAgents: Building a virtual pharma with large language model agents. arXiv 2025. [Google Scholar] [CrossRef]
- Gao, S.; Zhu, R.; Kong, Z.; Noori, A.; Su, X.; Ginder, C.; Tsiligkaridis, T.; Zitnik, M. TxAgent: An AI agent for therapeutic reasoning across a universe of tools. arXiv 2025. [Google Scholar] [CrossRef]
- Ghafarollahi, A.; Buehler, M.J. ProtAgents: Protein discovery via large language model multi-agent collaborations combining physics and machine learning. Digit. Discov. 2024, 3, 1389–1409. [Google Scholar] [CrossRef]
- Ghafarollahi, A.; Buehler, M.J. SciAgents: Automating scientific discovery through bioinspired multi-agent intelligent graph reasoning. Adv. Mater. 2025, 37, e2413523. [Google Scholar] [CrossRef] [PubMed]
- Ghareeb, A.E.; Chang, B.; Mitchener, L.; Yiu, A.; Szostkiewicz, C.J.; Shved, D.; Gyimesi, G.J.; Laurent, J.M.; Wright, S.M.; Razzak, M.T.; et al. A multi-agent system for automating scientific discovery. Nature 2026. [Google Scholar] [CrossRef] [PubMed]
- Gogna, A.; Arend, D.; Beier, S.; Rezaei, E.E.; Würschum, T.; Zhao, Y.; Chu, J.; Reif, J.C. Order from entropy: Big data from FAIR data cohorts in the digital age of plant breeding. Theor. Appl. Genet. 2025, 138, 257. [Google Scholar] [CrossRef] [PubMed]
- Gottweis, J.; Weng, W.-H.; Daryin, A.; Tu, T.; Sirkovic, P.; Myaskovsky, A.; Glowaty, G.; Weissenberger, F.; Orlandi, A.; Popovici, D.; et al. Accelerating scientific discovery with Co-Scientist. Nature 2026. [Google Scholar] [CrossRef]
- Guo, N.; Guo, J.; Liu, Y.; Wei, S.; Dong, L.; Du, H.; Bai, Y.; Zhao, Y.; Wang, X.; Zeng, D.; et al. MS4MS: LLMs-driven multi-agent system for small-molecule identification via LC-MS/MS. bioRxiv 2025. [Google Scholar]
- Heuermann, M.C.; Barros, P.; Beier, S.; Gundlach, H.; Alvarez-Jarreta, J.; Hassani-Pak, K.; König, P.; Fiebig, A.; Godec, T.; Gruden, K.; et al. White paper: Standards for handling and analyzing plant pan-genomes. F1000Research 2025, 14, 739. [Google Scholar] [CrossRef]
- Hou, X.; Zhao, Y.; Wang, S.; Wang, H. Model Context Protocol (MCP): Landscape, Security Threats, and Future Research Directions. arXiv 2025, arXiv:2503.23278. [Google Scholar] [CrossRef]
- Huang, K.; Zhang, S.; Wang, H.; Qu, Y.; Lu, Y.; Roohani, Y.; Li, R.; Qiu, L.; Li, G.; Zhang, J.; et al. Biomni: A General-Purpose Biomedical AI Agent. bioRxiv 2025. [Google Scholar] [CrossRef]
- Jin, D.; Gunner, N.; Carvajal Janke, N.; Baruah, S.; Gold, K.M.; Jiang, Y. Aleks: AI powered Multi Agent System for Autonomous Scientific Discovery via Data-Driven Approaches in Plant Science. arXiv 2025, arXiv:2508.19383. [Google Scholar] [CrossRef]
- Jin, Q.; Yang, Y.; Chen, Q.; Lu, Z. GeneGPT: Augmenting large language models with domain tools for improved access to biomedical information. Bioinformatics 2024, 40. [Google Scholar] [CrossRef]
- Jin, R.; Zhang, Z.; Wang, M.; Cong, L. STELLA: Self-Evolving LLM Agent for Biomedical Research. arXiv 2025, arXiv:2507.02004. [Google Scholar] [CrossRef]
- Ju, R.; Wang, X.; Ding, X.; Yang, Y.; Wu, H.; Jiang, S.; Zhang, Q.; Wen, H.; Li, X.; Wang, W.; et al. EmbodiSkill: Skill-Aware Reflection for Self-Evolving Embodied Agents. arXiv 2026, arXiv:2605.10332. [Google Scholar]
- Kaňovská, I.; Biová, J.; Škrabišová, M. New perspectives of post-GWAS analyses: From markers to causal genes for more precise crop breeding. Curr. Opin. Plant Biol. 2024, 82, 102658. [Google Scholar] [CrossRef] [PubMed]
- Lei, W.; Fuster-Barceló, C.; Reder, G.; Muñoz-Barrutia, A.; Ouyang, W. BioImage.IO Chatbot: A community-driven AI assistant for integrative computational bioimaging. Nat. Methods 2024, 21, 1368–1370. [Google Scholar] [CrossRef] [PubMed]
- Li, B.; Yan, T.; Pan, Y.; Luo, J.; Ji, R.; Ding, J.; Xu, Z.; Liu, S.; Dong, H.; Lin, Z.; et al. MMedAgent: Learning to Use Medical Tools with Multi-modal Agent. arXiv 2024. [Google Scholar]
- Li, J.; Jia, Y.; Li, F.; Su, X.; Luo, J.; Dong, Y.; Sun, C.; Cui, Q.; Wang, L.; Li, A.; et al. An AI-powered knowledge hub for potato functional genomics. Plant Commun. 2026, 7, 101730. [Google Scholar] [CrossRef]
- Li, J.; Lai, Y.; Li, W.; Ren, J.; Zhang, M.; Kang, X.; Wang, S.; Li, P.; Zhang, Y.-Q.; Ma, W.; et al. Agent Hospital: A Simulacrum of Hospital with Evolvable Medical Agents. arXiv 2024. [Google Scholar]
- Lin, Z.; Wang, W.; Marin-Llobet, A.; Li, Q.; Pollock, S.D. STAgent: Spatial transcriptomics AI agent charts hPSC-pancreas maturation in vivo. bioRxiv 2025. [Google Scholar]
- Liu, H.; Chen, S.; Zhang, Y.; Wang, H. GenoTEX: An LLM Agent Benchmark for Automated Gene Expression Data Analysis. arXiv 2024. [Google Scholar]
- Liu, S.; Lu, Y.; Chen, S.; Hu, X.; Zhao, J.; Lu, Y.; Zhao, Y. DrugAgent: Automating AI-aided drug discovery programming through LLM multi-agent collaboration. arXiv 2024. [Google Scholar]
- Liu, W.; Li, J.; Tang, Y.; Zhao, Y.; Liu, C.; Song, M.; Ju, Z.; Kumar, S.V.; Lu, Y.; Akbani, R.; et al. DrBioRight 2.0: An LLM-powered bioinformatics chatbot for large-scale cancer functional proteomics analysis. Nat. Commun. 2025, 16, 2256. [Google Scholar] [CrossRef]
- Liu, Y.; Zhou, L.; Du, X.; He, R.; Zhang, X.; Shen, R.; Li, Y. Benchmarking LLM-based agents for single-cell omics analysis. Genome Biol. 2026, 27, 123. [Google Scholar] [CrossRef] [PubMed]
- Lu, C.; Lu, C.; Lange, R.T.; Yamada, Y.; Hu, S.; Foerster, J.; Ha, D.; Clune, J. Towards end-to-end automation of AI research. Nature 2026, 651, 914–919. [Google Scholar] [CrossRef]
- Michael, T.P. Plant genome assembly and annotation. Curr. Opin. Plant Biol. 2026, 90, 102859. [Google Scholar] [CrossRef]
- Mitchener, L.; Laurent, J.M.; Andonian, A.; Tenmann, B.; Narayanan, S.; Wellawatte, G.P.; White, A.; Sani, L.; Rodriques, S.G. BixBench: A Comprehensive Benchmark for LLM-based Agents in Computational Biology. arXiv 2025, arXiv:2503.00096. [Google Scholar]
- Mölder, F.; Jablonski, K.P.; Letcher, B.; Hall, M.B.; van Dyken, P.C.; Tomkins-Tinch, C.H.; Sochat, V.; Forster, J.; Vieira, F.G.; Meesters, C.; et al. Sustainable data analysis with Snakemake. F1000Research 2021, 10, 33. [Google Scholar] [CrossRef]
- Nicholas, M.; Hyunjun, C.; Jay, M.; Miguel, E.H.; Mythreye, V.; Xi, L.; Jui-Hsuan, C.; Paul, W.; Jason, H.M. ESCARGOT: An AI Agent Integrating Graph-of-Thought and Biomedical Knowledge Graphs. Bioinformatics 2025. [Google Scholar]
- Nikita, M.; Amanda, K.H.; Olesya, M.; Yulia, D.; Daniel, T.; David, B.; Ahmed, A.; Scott, S.; Venkat, S.M. BioAgents: Bridging the gap in bioinformatics analysis with multi-agent systems. Sci. Rep. 2025. [Google Scholar]
- Olson, A.; Kumari, S.; Wei, X.; Chougule, K.; Lu, Z.; Tello-Ruiz Marcela, K.; Kumar, V.; Van Buren, P.; Olson, A.; Kim, C.; et al. Gramene 2025: Expanded comparative genomics and pathway resources, integrated search, and pan-genome portals for crop research. Nucleic Acids Res. 2026, 54, D1720–D1732. [Google Scholar] [CrossRef] [PubMed]
- Politsch, J.E.; González-Delgado, A.; Wabnik, K. From big data to mechanistic insights: Decoding plant complexity with models. Curr. Opin. Biotechnol. 2026, 97, 103428. [Google Scholar] [CrossRef]
- PromptBio, T. PromptBio: A Modular Multi-Agent AI Platform for Bioinformatics Analysis. bioRxiv 2025. [Google Scholar]
- Qi, C.; Wang, W.; Jiang, S.; Liu, Q.; Song, X.; Fang, H.; Wei, Z. Artificial Intelligence agents for biological research: A survey. Brief. Bioinform. 2026, 27. [Google Scholar] [CrossRef]
- Qu, Y.; Huang, K.; Yin, M.; Zhan, K.; Liu, D.; Yin, D.; Cousins, H.C.; Johnson, W.A.; Wang, X.; Shah, M.; et al. CRISPR-GPT for agentic automation of gene-editing experiments. Nat. Biomed. Eng. 2026, 10, 245–258. [Google Scholar] [CrossRef]
- Qu, Y.; Lu, Y.; Tu, X.; Zhang, S.; She, T.; Shaw, A.G.; Shih, J.-H.; Zhao, B.; Shen, M.; Yang, H.; et al. BiomniBench: Process-level Evaluation of LLM Agents for Real-world Biomedical Research. bioRxiv 2026. [Google Scholar]
- Reiter, T.; Brooks, P.T.; Irber, L.; Joslin, S.E.K.; Reid, C.M.; Scott, C.; Brown, C.T.; Pierce-Ward, N.T. Streamlining data-intensive biology with workflow systems. GigaScience 2021, 10. [Google Scholar] [CrossRef] [PubMed]
- Robinson, M.D.; Cai, P.; Emons, M.; Gerber, R.; Germain, P.-L.; Gunz, S.; Luo, S.; Moro, G.; Sonder, E.; Sonrel, A.; et al. Ten simple rules for computational biologists collaborating with wet lab researchers. PLoS Computational Biol. 2024, 20, e1012174. [Google Scholar] [CrossRef] [PubMed]
- Roohani, Y.; Lee, A.; Huang, Q.; Vora, J.; Steinhart, Z.; Huang, K.; Marson, A.; Liang, P.; Leskovec, J. BioDiscoveryAgent: An AI Agent for Designing Genetic Perturbation Experiments. arXiv 2024, arXiv:2405.17631. [Google Scholar]
- Ruofan, J.; Yucheng, G.; Yuanhao, Q.; Ming, Y.; Qirong, Y.; Linlin, C.; Chun, S.; Yi, Z.; Ruilai, X.; Ziyao, X. BioLab: End-to-End Autonomous Life Sciences Research with Multi-Agents System Integrating Biological Foundation Models. bioRxiv 2025. [Google Scholar]
- Salzberg, S.L. Next-generation genome annotation: We still struggle to get it right. Genome Biol. 2019, 20, 92. [Google Scholar] [CrossRef]
- Schmidgall, S.; Su, Y.; Wang, Z.; Sun, X.; Wu, J.; Yu, X.; Liu, J.; Moor, M.; Liu, Z.; Barsoum, E. Agent Laboratory: Using LLM agents as research assistants. arXiv 2025. [Google Scholar] [CrossRef]
- Shi, J.; Tian, Z.; Lai, J.; Huang, X. Plant pan-genomics and its applications. Mol. Plant 2023, 16, 168–186. [Google Scholar] [CrossRef] [PubMed]
- Stark, R.; Grzelak, M.; Hadfield, J. RNA sequencing: The teenage years. Nat. Rev. Genet. 2019, 20, 631–656. [Google Scholar] [CrossRef]
- Su, H.; Feng, J.; Lu, Y.; Xu, Y.; Yang, J.; Lu, H.; Yang, J.; Yang, X.; Xie, S.; Long, W.; et al. BioMaster: Multi-agent system for automated bioinformatics analysis workflow. bioRxiv 2025. [Google Scholar]
- Sunghyun, K.; Seokwoo, Y.; Youngseo, Y.; Youngrak, L.; Sangsoo, L. MARBLE: Multi-Agent Reasoning for Bioinformatics Learning and Evolution. arXiv 2026. [Google Scholar] [CrossRef]
- Swanson, K.; Wu, W.; Bulaong, N.L.; Pak, J.E.; Zou, J. The Virtual Lab of AI agents designs new SARS-CoV-2 nanobodies. Nature 2025, 646, 716–723. [Google Scholar] [CrossRef]
- Tang, X.; Qian, B.; Gao, R.; Chen, J.; Chen, X.; Gerstein, M.B. BioCoder: A benchmark for bioinformatics code generation with large language models. Bioinformatics 2024, 40, i266–i276. [Google Scholar] [CrossRef]
- Tang, X.; Yu, Z.; Chen, J.; Cui, Y.; Shao, D.; Wang, W.; Wu, F.; Zhuang, Y.; Shi, W.; Huang, Z.; et al. CellForge: Agentic Design of Virtual Cell Models. arXiv 2025, arXiv:2508.02276. [Google Scholar]
- Tang, X.; Zou, A.; Zhang, Z.; Li, Z.; Zhao, Y.; Zhang, X.; Cohan, A.; Gerstein, M. MedAgents: Large Language Models as Collaborators for Zero-shot Medical Reasoning. arXiv 2023. [Google Scholar]
- Tie, G.; Shi, J.; Song, D.; Huang, Y.; Sheng, Z.; Zhou, X.; Liu, D.; Zhou, P.; Chen, Y.; Xu, R.; et al. AutoResearch AI: Towards AI-Powered Research Automation for Scientific Discovery. arXiv 2026, arXiv:2605.23204. [Google Scholar]
- Tom, G.; Schmid, S.P.; Baird, S.G.; Cao, Y.; Darvish, K.; Hao, H.; Lo, S.; Pablo-García, S.; Rajaonson, E.M.; Skreta, M.; et al. Self-Driving Laboratories for Chemistry and Materials Science. Chem. Rev. 2024, 124, 9633–9732. [Google Scholar] [CrossRef]
- Vlastimil, M.; Andrea, G.; Dimosthenis, T.; Aitor Alberdi, E.; Edward, B.; David, C.; Luke, C.; Alessandro, B.; Panagiotis, A. Agentomics-ML: Autonomous Machine Learning Experimentation Agent for Genomic and Transcriptomic Data. arXiv 2024. [Google Scholar]
- volcanooooooooo (2026). ABC: Agricultural Breeding Claw—An AI-Powered Agricultural Breeding Research Assistant (GitHub).
- Wang, H.; He, Y.; Coelho, P.P.; Bucci, M. SpatialAgent: An Autonomous AI Agent for Spatial Biology. bioRxiv 2025. [Google Scholar] [CrossRef]
- Wang, Z.; Jin, Q.; Wei, C.-H.; Tian, S.; Lai, P.-T.; Zhu, Q.; Day, C.-P.; Ross, C.; Leaman, R.; Lu, Z. GeneAgent: Self-verification language agent for gene-set analysis using domain databases. Nat. Methods 2025b, 22, 1677–1685. [Google Scholar] [CrossRef] [PubMed]
- Wang, Z.; Liang, C.; Zhang, X.; Wei, W.; Li, K. BOLE: A Knowledge-Enhanced Multi-Agent Framework for Intelligent Genomic Breeding. bioRxiv 2026. [Google Scholar]
- Wei, X.; Gang, L.; Weiyu, M.; Xiaobing, Z.; Keli, Z.; Ji, W.; Yanrong, L.; Abao, X.; Junrong, L.; Zhifan, L.; et al. MRAgent: An LLM-based Automated Agent for Causal Knowledge Discovery in Disease via Mendelian Randomization. Brief. Bioinform. 2025. [Google Scholar]
- Widjaja, F.; Chen, Z.; Zhou, J. BioinfoMCP: A Unified Platform Enabling MCP Interfaces in Agentic Bioinformatics. arXiv 2025, arXiv:2510.02139. [Google Scholar] [CrossRef]
- Williamson, H.F.; Brettschneider, J.; Caccamo, M.; Davey, R.P.; Goble, C.; Kersey, P.J.; May, S.; Morris, R.J.; Ostler, R.; Pridmore, T.; et al. Data management challenges for artificial intelligence in plant and agricultural research. F1000Research 2021, 10, 324. [Google Scholar] [CrossRef]
- Wratten, L.; Wilm, A.; Göke, J. Reproducible, scalable, and shareable analysis pipelines with bioinformatics workflow managers. Nat. Methods 2021, 18, 1161–1168. [Google Scholar] [CrossRef]
- Xiao, Y.; Liu, J.; Zheng, Y.; Jiao, S.; Hao, J.; Xie, X.; Li, M.; Wang, R.; Ni, F.; Li, Y.; et al. CellAgent: An LLM-driven multi-agent framework for automated single-cell data analysis. bioRxiv 2024. [Google Scholar]
- Xie, Y.; Zhang, T.; Yang, M.; Lyu, H.; Zou, Y.; Sun, Y.; Xiao, J.; Lian, W.; Tao, J.; Han, H.; et al. Engineering crop flower morphology facilitates robotization of cross-pollination and speed breeding. Cell 2025, 188, 5809–5830.e5827. [Google Scholar] [CrossRef]
- Xin, Q.; Kong, Q.; Ji, H.; Shen, Y.; Liu, Y.; Sun, Y.; Zhang, Z.; Li, Z.; Xia, X.; Deng, B.; et al. BioInformatics Agent (BIA): Unleashing the Power of Large Language Models to Reshape Bioinformatics Workflow. bioRxiv 2024. [Google Scholar] [CrossRef]
- Xu, F.; Cheng, Q.; Liu, S.; Jiang, S.; Zhang, J.; Mao, X.; Wang, X.; Lai, J.; Yan, J. MRBIGR: A versatile toolbox for genetic regulation inference from population-scale multi-omics data. Plant Commun. 2025, 6, 101197. [Google Scholar] [CrossRef] [PubMed]
- Xu, F.; Wu, T.; Cheng, Q.; Wang, X.; Yan, J. Foundation models in plant molecular biology: Advances, challenges, and future directions. Front. Plant Sci. 2025, 16. [Google Scholar] [CrossRef] [PubMed]
- Xu, X.; Feng, C.; Zha, C.; He, W.; He, M.; Xiao, B.; Gao, X. ProteinMCP: An Agentic AI Framework for Autonomous Protein Engineering. bioRxiv 2026. [Google Scholar] [CrossRef]
- Yang, E.-W.; Waldrup, B.; Velazquez-Villarreal, E. Conversational AI agent for precision oncology: AI-HOPE-WNT integrates clinical and genomic data to investigate WNT pathway dysregulation in colorectal cancer. Front. Artif. Intell. 2025, 8. [Google Scholar] [CrossRef] [PubMed]
- Yang, F.; Kong, H.; Ying, J.; Chen, Z.; Luo, T.; Jiang, W.; Yuan, Z.; Wang, Z.; Ma, Z.; Wang, S.; et al. SeedLLM·Rice: A large language model integrated with rice biological knowledge graph. Mol. Plant 2025, 18, 1118–1129. [Google Scholar] [CrossRef]
- Yang, T.; Xiao, Y.; Bao, Z.; Hao, J.; Peng, J. The rise and potential opportunities of large language model agents in bioinformatics and biomedicine. Brief. Bioinform. 2025, 26, bbaf601. [Google Scholar] [CrossRef]
- Yu, H.; Zhou, S.; Huang, M.; Ding, L.; Chen, Y.; Wang, Y.; Ren, Y.; Cheng, N.; Wang, X.; Liang, J.; et al. PlantScience.ai: An LLM-powered virtual scientist for plant science. Mol. Plant 2026, 19, 1117–1123. [Google Scholar] [CrossRef]
- Zhang, D.; Xu, F.; Wang, F.; Le, L.; Pu, L. Synthetic biology and artificial intelligence in crop improvement. Plant Commun. 2025, 6. [Google Scholar] [CrossRef]
- Zhang, G.; Zhu, E.; Zhou, J.; Jia, C.; Wang, H. SkillEvolver: Skill Learning as a Meta-Skill. arXiv 2026, arXiv:2605.10500. [Google Scholar] [CrossRef]
- Zhang, R.; Wang, Y.; Yang, W.; Wen, J.; Liu, W.; Zhi, S.; Li, G.; Chai, N.; Huang, J.; Xie, Y.; et al. PlantGPT: An Arabidopsis-Based Intelligent Agent that Answers Questions about Plant Functional Genomics. Adv. Sci. 2025, 12, e03926. [Google Scholar] [CrossRef]
- Zhang, Z.; Wang, Y.; Wang, C.; Chen, J.; Zheng, Z. LLM Hallucinations in Practical Code Generation: Phenomena, Mechanism, and Mitigation. arXiv 2024, arXiv:2409.20550. [Google Scholar] [CrossRef]
- Zhou, J.; Zhang, B.; Li, G.; Chen, X.; Li, H.; Xu, X.; Chen, S.; He, W.; Xu, C.; Liu, L.; et al. An AI Agent for Fully Automated Multi-Omic Analyses. Adv. Sci. 2024, 11, 2407094. [Google Scholar] [CrossRef]
- Zhou, L.; Ling, H.; Fu, C.; Huang, Y.; Sun, M.; Yu, W.; Wang, X.; Li, X.; Su, X.; Zhang, J.; et al. Autonomous Agents for Scientific Discovery: Orchestrating Scientists, Language, Code, and Physics. arXiv 2025, arXiv:2510.09901. [Google Scholar]
- Zuo, K.; Jiang, Y.; Mo, F.; Lio, P. KG4Diagnosis: A Hierarchical Multi-Agent LLM Framework with Knowledge Graph Enhancement for Medical Diagnosis. arXiv 2024. [Google Scholar]



| Agent Level | Core Capability | Minimum Qualifying Criterion | Boundary/Not Sufficient | Evidence Status in Plant Genomics | Human Role |
|---|---|---|---|---|---|
| L1 Knowledge integration | Retrieve, reconcile and cite distributed literature, database and multi-omics evidence with provenance | External evidence sources are retrieved, cited and linked to a plant-science question | Ungrounded summarisation, citation-free answers, or gene descriptions without provenance | Supported: several plant-focused systems, mostly at retrieval/curation/knowledge-graph level (Table S1) | Judge biological plausibility and causal interpretation |
| L2 Tool orchestration | Translate a biological question into executable, logged, reproducible multi-step workflows | External tools, files and parameters are invoked, logged and checked with limited human intervention | A static script or preset workflow without adaptive selection, monitoring or audit; execution that stops at summarisation | Emerging: early plant phenotyping/breeding prototypes; broader support from cross-domain bioinformatics agents and WMS (Table S1) | Approve context-sensitive assumptions and high-impact analytical choices |
| L3 Closed-loop computational discovery | Iterative hypothesis generation, computational testing and refinement, where each cycle changes the next analysis or ranking | ≥3 autonomous hypothesis–test–refinement cycles on a defined plant-science task, with improvement across cycles | A multi-step report or one-pass workflow where later tests do not depend on earlier outputs; does not establish causality without wet-lab/field validation | Open target: no general, peer-reviewed, well-benchmarked plant system yet meets the criterion (Table S1) | Decide whether refined hypotheses justify experimental follow-up |
| L4 Self-evolving systems | Improve reusable tools, workflows or sub-agents across repeated projects | Validated, reusable capability gains demonstrated across tasks and independently reused | Memory, self-prompting or ad hoc code generation without validated, reusable improvement | Speculative: no plant-specific evidence; cross-domain examples are conceptual comparators only (Table S1) | Govern adoption, validation scope and responsibility for system evolution |
| Design Requirement | Why it Matters in Plant Genomics | Required Implementation Feature | Audit Evidence to Report |
|---|---|---|---|
| Source-grounded knowledge retrieval | Evidence scattered across species, genome versions, identifiers and publication types | Tie every claim to citation, species, gene model and genome build | Source list; citation trace; evidence-type labels; identifier conflicts |
| Version-aware data handling | Interpretation shifts with assembly, annotation, coordinate system or gene model | Record reference genome, annotation version, coordinate conversion and database release | Version log; checksum; mapping table; build-mismatch warnings |
| Workflow-manager-backed execution | Manual reconstruction of commands and parameters is unreliable | Prefer reusable workflows/established tools; limit generated code to local transformations | Command log; environment file; parameters; software versions; rerun steps |
| Failure detection and escalation | Silent failures yield plausible but biologically wrong rankings | Catch missing inputs, bad formats, failed steps and consequential inconsistencies | Error log; failed-step report; human-review flag |
| Provenance-preserving reasoning | Prioritisation rests on partial, weighted evidence, not one label | Record which evidence changed each ranking update | Decision trace; evidence-to-rank mapping |
| Human-in-the-loop governance | Breeding and experimental decisions are costly, slow or irreversible | Require explicit approval for high-cost decisions and sensitive data | Approval checkpoint; data-access log; decision owner; privacy record |
| Deployment Risk | Plant-Genomics Manifestation | Decision Gate | Residual Risk |
|---|---|---|---|
| Hallucinated or weakly grounded evidence | Wrong gene–trait claims, unsupported orthology transfer, overconfident annotation | No candidate nomination without a complete, reviewable evidence trace | Wrong chains persist if source databases are incomplete |
| Irreproducible computational workflow | Missing versions, undocumented parameters, non-rerunnable scripts | No reported result without rerun instructions and a provenance record | A reproducible command may still encode a wrong analytical choice |
| Genome-build or identifier mismatch | Genes mapped to the wrong assembly, annotation or coordinate system | Human review when build/identifier conflicts affect interpretation | Legacy annotations and minor crops may stay weakly covered |
| Over-automation of biological inference | Association or expression correlation treated as causal function | Never present a candidate ranking as experimental proof | Causality unestablished until wet-lab/field validation |
| Cross-crop non-transfer | Evidence from one crop applied to another without justification | Require crop-specific validation and stated uncertainty before cross-species claims | True biological non-equivalence may stay computationally unresolved |
| Benchmark overfitting | Good on curated tasks, poor on messy crop data | Do not infer field readiness from public benchmarks alone | Incomplete crop coverage remains possible |
| Governance and privacy failure | Proprietary germplasm or field data exposed to unsuitable services | No sensitive-data processing without documented approval and deployment limits | Governance limits may cap full reproducibility |
| Cultural and operational adoption | Opaque recommendations distrusted or un-inspectable | Deploy first in triage/review before high-cost breeding decisions | Trust may stay low where outputs conflict with local expertise |
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