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  • Review
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Integrated biotechnological and AI innovations for crop improvement

Abstract

Crops provide food, clothing and other important products for the global population. To meet the demands of a growing population, substantial improvements are required in crop yield, quality and production sustainability. However, these goals are constrained by various environmental factors and limited genetic resources. Overcoming these limitations requires a paradigm shift in crop improvement by fully leveraging natural genetic diversity alongside biotechnological approaches such as genome editing and the heterologous expression of designed proteins, coupled with multimodal data integration. In this Review, we provide an in-depth analysis of integrated uses of omics technologies, genome editing, protein design and high-throughput phenotyping, in crop improvement, supported by artificial intelligence-enabled tools. We discuss the emerging applications and current challenges of these technologies in crop improvement. Finally, we present a perspective on how elite alleles generated through these technologies can be incorporated into the genomes of existing and de novo domesticated crops, aided by a proposed artificial intelligence model. We suggest that integrating these technologies with agricultural practices will lead to a new revolution in crop improvement, contributing to global food security in a sustainable manner.

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Fig. 1: Genome editing for crop improvement.
Fig. 2: Protein design in crop improvement.
Fig. 3: HTP accelerates crop improvement.

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References

  1. van Dijk, M. et al. A meta-analysis of projected global food demand and population at risk of hunger for the period 2010–2050. Nat. Food 2, 494–501 (2021).

    PubMed  Google Scholar 

  2. Hasegawa, T. et al. Extreme climate events increase risk of global food insecurity and adaptation needs. Nat. Food 2, 587–595 (2021).

    PubMed  Google Scholar 

  3. Zhang, H. et al. A Gγ protein regulates alkaline sensitivity in crops. Science 379, eade8416 (2023).

    CAS  PubMed  Google Scholar 

  4. Singh, B. K. et al. Climate change impacts on plant pathogens, food security and paths forward. Nat. Rev. Microbiol. 21, 640–656 (2023).

    CAS  PubMed  Google Scholar 

  5. Potapov, P. et al. Global maps of cropland extent and change show accelerated cropland expansion in the twenty-first century. Nat. Food 3, 19–28 (2022).

    PubMed  Google Scholar 

  6. Crow, J. F. 90 years ago: the beginning of hybrid maize. Genetics 148, 923–928 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Pingali, P. L. Green revolution: impacts, limits, and the path ahead. Proc Natl Acad. Sci. USA 109, 12302–12308 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Green, J. M. The benefits of herbicide-resistant crops. Pest. Manag. Sci. 68, 1323–1331 (2012).

    CAS  PubMed  Google Scholar 

  9. Lu, Y. et al. Widespread adoption of Bt cotton and insecticide decrease promotes biocontrol services. Nature 487, 362–365 (2012).

    CAS  PubMed  Google Scholar 

  10. Mascher, M. et al. Promises and challenges of crop translational genomics. Nature 636, 585–593 (2024).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Yu, X. et al. Single-cell and spatial multi-omics in the plant sciences: technical advances, applications, and perspectives. Plant Commun. 4, 100508 (2023).

    PubMed  Google Scholar 

  12. Yu, H. et al. A route to de novo domestication of wild allotetraploid rice. Cell 184, 1156–1170 (2021). This study demonstrates the rapid neo-domestication of wild rice relatives, a new paradigm in enriching crop genetic resources and accelerating crop improvement.

    CAS  PubMed  Google Scholar 

  13. Li, T. et al. Domestication of wild tomato is accelerated by genome editing. Nat. Biotechnol. 36, 1160–1163 (2018).

    CAS  Google Scholar 

  14. Abramson, J. et al. Accurate structure prediction of biomolecular interactions with AlphaFold 3. Nature 630, 493–500 (2024).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Kortemme, T. De novo protein design—from new structures to programmable functions. Cell 187, 526–544 (2024).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Silver, D. et al. Mastering the game of Go with deep neural networks and tree search. Nature 529, 484–489 (2016).

    CAS  PubMed  Google Scholar 

  17. Listov, D. et al. Opportunities and challenges in design and optimization of protein function. Nat. Rev. Mol. Cell Biol. 25, 639–653 (2024).

    CAS  PubMed  Google Scholar 

  18. Yang, W. et al. Crop phenomics and high-throughput phenotyping: past decades, current challenges, and future perspectives. Mol. Plant 13, 187–214 (2020).

    CAS  PubMed  Google Scholar 

  19. Shen, S. et al. Metabolomics-centered mining of plant metabolic diversity and function: Past decade and future perspectives. Mol. Plant 16, 43–63 (2023).

    CAS  PubMed  Google Scholar 

  20. Li, B. et al. Targeted genome-modification tools and their advanced applications in crop breeding. Nat. Rev. Genet. 25, 603–622 (2024).

    CAS  PubMed  Google Scholar 

  21. Scossa, F. et al. Integrating multi-omics data for crop improvement. J. Plant Physiol. 257, 153352 (2021).

    CAS  PubMed  Google Scholar 

  22. Torres-Rodríguez, J. V. et al. Evolving best practices for transcriptome-wide association studies accelerate discovery of gene-phenotype links. Curr. Opin. Plant Biol. 83, 102670 (2025).

    PubMed  Google Scholar 

  23. Goff, S. A. et al. A draft sequence of the rice genome (Oryza sativa L. ssp. japonica). Science 296, 92–100 (2002).

    CAS  PubMed  Google Scholar 

  24. Li, H. & Durbin, R. Genome assembly in the telomere-to-telomere era. Nat. Rev. Genet. 25, 658–670 (2024).

    CAS  PubMed  Google Scholar 

  25. Chen, J. et al. A complete telomere-to-telomere assembly of the maize genome. Nat. Genet. 55, 1221–1231 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Qin, P. et al. Pan-genome analysis of 33 genetically diverse rice accessions reveals hidden genomic variations. Cell 184, 3542–3558 (2021).

    CAS  PubMed  Google Scholar 

  27. Tang, D. et al. Genome evolution and diversity of wild and cultivated potatoes. Nature 606, 535–541 (2022). Sequencing and analysis of genomes from wild and cultivated potatoes enables identification of candidate genes for many traits, including a transcription factor for tuber formation.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Liu, Y. et al. Pan-genome of wild and cultivated soybeans. Cell 182, 162–176 (2020).

    CAS  PubMed  Google Scholar 

  29. Hufford, M. B. et al. De novo assembly, annotation, and comparative analysis of 26 diverse maize genomes. Science 373, 655–662 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Jayakodi, M. et al. Structural variation in the pangenome of wild and domesticated barley. Nature 636, 654–662 (2024).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Jiao, C. et al. Pan-genome bridges wheat structural variations with habitat and breeding. Nature 637, 384–393 (2024).

    PubMed  Google Scholar 

  32. Sun, W. et al. Genetic modification of Gγ subunit AT1 enhances salt-alkali tolerance in main graminaceous crops. Natl Sci. Rev. 10, nwad075 (2023). This study demonstrates that elite alleles cloned from one crop can be rapidly translated into other crops, facilitated by crop genomics, mutant collections and genome editing.

    PubMed  PubMed Central  Google Scholar 

  33. Varshney, R. K. et al. A chickpea genetic variation map based on the sequencing of 3,366 genomes. Nature 599, 622–627 (2021). This study demonstrates some valuable breeding strategies from sequencing and analysis of cultivated and wild chickpea accessions.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Wei, X. et al. Genomic investigation of 18,421 lines reveals the genetic architecture of rice. Science 385, eadm8762 (2024).

    CAS  PubMed  Google Scholar 

  35. Cheng, S. et al. Harnessing landrace diversity empowers wheat breeding. Nature 632, 823–831 (2024). This study provides a framework for fully utilizing genetic diversity in more than 1,000 wheat landraces and cultivars for wheat improvement through sequencing and in-depth field phenotyping.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Zhang, J. et al. Releasing a sugar brake generates sweeter tomato without yield penalty. Nature 635, 647–656 (2024).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Zhang, Y. et al. Structural variation reshapes population gene expression and trait variation in 2,105 Brassica napus accessions. Nat. Genet. 56, 2538–2550 (2024).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Wang, W. et al. Genomic variation in 3,010 diverse accessions of Asian cultivated rice. Nature 557, 43–49 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Yang, N. et al. Two teosintes made modern maize. Science 382, eadg8940 (2023).

    CAS  PubMed  Google Scholar 

  40. Gu, Z. et al. Structure and function of rice hybrid genomes reveal genetic basis and optimal performance of heterosis. Nat. Genet. 55, 1745–1756 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Wu, Y. et al. Phylogenomic discovery of deleterious mutations facilitates hybrid potato breeding. Cell 186, 2313–2328 (2023).

    CAS  PubMed  Google Scholar 

  42. Alemu, A. et al. Genomic selection in plant breeding: key factors shaping two decades of progress. Mol. Plant 17, 552–578 (2024).

    CAS  PubMed  Google Scholar 

  43. Mueller, U. G. & Linksvayer, T. A. Microbiome breeding: conceptual and practical issues. Trends Microbiol. 30, 997–1011 (2022).

    CAS  PubMed  Google Scholar 

  44. Schmitz, L. et al. Synthetic bacterial community derived from a desert rhizosphere confers salt stress resilience to tomato in the presence of a soil microbiome. ISME J. 16, 1907–1920 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Yue, H. et al. Host genotype-specific rhizosphere fungus enhances drought resistance in wheat. Microbiome 12, 44 (2024).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Kwak, M.-J. et al. Rhizosphere microbiome structure alters to enable wilt resistance in tomato. Nat. Biotechnol. 36, 1100–1109 (2018).

    CAS  Google Scholar 

  47. Zhang, L. et al. A highly conserved core bacterial microbiota with nitrogen-fixation capacity inhabits the xylem sap in maize plants. Nat. Commun. 13, 3361 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Huang, R. et al. Natural variation at OsCERK1 regulates arbuscular mycorrhizal symbiosis in rice. New Phytol. 225, 1762–1776 (2020).

    CAS  PubMed  Google Scholar 

  49. Zhang, J. et al. NRT1.1B is associated with root microbiota composition and nitrogen use in field-grown rice. Nat. Biotechnol. 37, 676–684 (2019).

    CAS  PubMed  Google Scholar 

  50. Su, P. et al. Microbiome homeostasis on rice leaves is regulated by a precursor molecule of lignin biosynthesis. Nat. Commun. 15, 23 (2024).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Weisberg, A. J. et al. Genomic approaches to plant-pathogen epidemiology and diagnostics. Annu. Rev. Phytopathol. 59, 311–332 (2021).

    CAS  PubMed  Google Scholar 

  52. Thilliez, G. J. A. et al. Pathogen enrichment sequencing (PenSeq) enables population genomic studies in oomycetes. New Phytol. 221, 1634–1648 (2019).

    PubMed  Google Scholar 

  53. Brooks, E. G. et al. Plant promoters and terminators for high-precision bioengineering. Biodes. Res. 5, 0013 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Gabriel, L. et al. BRAKER3: fully automated genome annotation using RNA-seq and protein evidence with GeneMark-ETP, AUGUSTUS, and TSEBRA. Genome Res. 34, 769–777 (2024).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Yang, C. et al. Rice metabolic regulatory network spanning the entire life cycle. Mol. Plant 15, 258–275 (2022).

    CAS  PubMed  Google Scholar 

  56. Zhu, G. et al. Rewiring of the fruit metabolome in tomato breeding. Cell 172, 249–261 (2018). This study uses metabolomics to demonstrate how breeding has made tomato more edible.

    CAS  PubMed  Google Scholar 

  57. Sreenivasulu, N. et al. Metabolic signatures from genebank collections: an underexploited resource for human health? Annu. Rev. Food Sci. Technol. 14, 183–202 (2023).

    PubMed  Google Scholar 

  58. Bai, Y. et al. Natural history-guided omics reveals plant defensive chemistry against leafhopper pests. Science 375, eabm2948 (2022).

    CAS  PubMed  Google Scholar 

  59. Sha, G. et al. Genome editing of a rice CDP-DAG synthase confers multipathogen resistance. Nature 618, 1017–1023 (2023). Saturated targeted mutagenesis enabled by multiplexed genome editing optimizes the RBL1 allele in balancing immunity and growth, making the unusable allele valuable in rice breeding.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Michaelis, A. C. et al. The social and structural architecture of the yeast protein interactome. Nature 624, 192–200 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Bilbao, A. et al. PeakDecoder enables machine learning-based metabolite annotation and accurate profiling in multidimensional mass spectrometry measurements. Nat. Commun. 14, 2461 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Alseekh, S. & Fernie, A. R. Metabolomics 20 years on: what have we learned and what hurdles remain? Plant J. 94, 933–942 (2018).

    CAS  PubMed  Google Scholar 

  63. Marand, A. P. et al. A cis-regulatory atlas in maize at single-cell resolution. Cell 184, 3041–3055 (2021).

    CAS  PubMed  Google Scholar 

  64. Swift, J. et al. Exaptation of ancestral cell-identity networks enables C4 photosynthesis. Nature 636, 143–150 (2024).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Ortiz-Ramírez, C. et al. Ground tissue circuitry regulates organ complexity in maize and Setaria. Science 374, 1247–1252 (2021).

    PubMed  PubMed Central  Google Scholar 

  66. Omary, M. et al. A conserved superlocus regulates above- and belowground root initiation. Science 375, eabf4368 (2022).

    CAS  PubMed  Google Scholar 

  67. Zhang, T. Q. et al. Single-cell transcriptome atlas and chromatin accessibility landscape reveal differentiation trajectories in the rice root. Nat. Commun. 12, 2053 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Wang, Q. et al. Single-cell transcriptome atlas reveals developmental trajectories and a novel metabolic pathway of catechin esters in tea leaves. Plant Biotechnol. J. 20, 2089–2106 (2022).

    PubMed  PubMed Central  Google Scholar 

  69. Wang, H. et al. Molecular regulation of oil gland development and biosynthesis of essential oils in Citrus spp. Science 383, 659–666 (2024).

    CAS  PubMed  Google Scholar 

  70. Li, C. et al. Single-cell multi-omics in the medicinal plant Catharanthus roseus. Nat. Chem. Biol. 19, 1031–1041 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Xu, X. et al. Single-cell RNA sequencing of developing maize ears facilitates functional analysis and trait candidate gene discovery. Dev. Cell 56, 557–568 (2021). This study integrates single-cell omics with GWASs in crops to identify genes associated with yield.

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Nobori, T. et al. A rare PRIMER cell state in plant immunity. Nature 638, 197–205 (2025).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Serrano, K. et al. Spatial co-transcriptomics reveals discrete stages of the arbuscular mycorrhizal symbiosis. Nat. Plants 10, 673–688 (2024).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Liu, Z. et al. Single-nucleus transcriptomes reveal spatiotemporal symbiotic perception and early response in Medicago. Nat. Plants 9, 1734–1748 (2023).

    CAS  PubMed  Google Scholar 

  75. Rhaman, M. S. et al. Opportunities and challenges in advancing plant research with single-cell omics. Genomics Proteomics Bioinformatics 22, qzae026 (2024).

    PubMed  PubMed Central  Google Scholar 

  76. Qin, Y. et al. Single-cell RNA-seq reveals fate determination control of an individual fibre cell initiation in cotton (Gossypium hirsutum). Plant Biotechnol. J. 20, 2372–2388 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Wang, Y. et al. A spatial transcriptome map of the developing maize ear. Nat. Plants 10, 815–827 (2024).

    CAS  PubMed  Google Scholar 

  78. Chau, T. N. et al. Advancing plant single-cell genomics with foundation models. Curr. Opin. Plant Biol. 82, 102666 (2024).

    CAS  PubMed  Google Scholar 

  79. Zhang, X. et al. A spatially resolved multi-omic single-cell atlas of soybean development. Cell 188, 550–567 (2024).

    PubMed  Google Scholar 

  80. Tosches, M. A. & Lee, H. J. Cellular atlases of the entire mouse brain. Nature 624, 253–255 (2023).

    CAS  PubMed  Google Scholar 

  81. Tuncel, A., Pan, C., Clem, J. S., Liu, D. & Qi, Y. CRISPR–Cas applications in agriculture and plant research. Nat. Rev. Mol. Cell Biol. 26, 419–441 (2025).

    CAS  PubMed  Google Scholar 

  82. Liu, H. J. et al. High-throughput CRISPR/Cas9 mutagenesis streamlines trait gene identification in maize. Plant Cell 32, 1397–1413 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Bai, M. et al. Generation of a multiplex mutagenesis population via pooled CRISPR–Cas9 in soya bean. Plant Biotechnol. J. 18, 721–731 (2020).

    CAS  PubMed  Google Scholar 

  84. Meng, X. et al. Construction of a genome-wide mutant library in rice using CRISPR/Cas9. Mol. Plant 10, 1238–1241 (2017).

    CAS  PubMed  Google Scholar 

  85. Bi, M. et al. Construction of transcription factor mutagenesis population in tomato using a pooled CRISPR/Cas9 plasmid library. Plant Physiol. Biochem. 205, 108094 (2023).

    CAS  PubMed  Google Scholar 

  86. He, J. et al. Genome-scale targeted mutagenesis in Brassica napus using a pooled CRISPR library. Genome Res. 33, 798–809 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Li, C. et al. Targeted, random mutagenesis of plant genes with dual cytosine and adenine base editors. Nat. Biotechnol. 38, 875–882 (2020).

    CAS  PubMed  Google Scholar 

  88. Xu, R. et al. Identification of herbicide resistance OsACC1 mutations via in planta prime-editing-library screening in rice. Nat. Plants 7, 888–892 (2021).

    CAS  PubMed  Google Scholar 

  89. Beying, N. et al. CRISPR–Cas9-mediated induction of heritable chromosomal translocations in Arabidopsis. Nat. Plants 6, 638–645 (2020).

    CAS  PubMed  Google Scholar 

  90. Rönspies, M. et al. CRISPR–Cas-mediated chromosome engineering for crop improvement and synthetic biology. Nat. Plants 7, 566–573 (2021).

    PubMed  Google Scholar 

  91. Sun, C. et al. Precise integration of large DNA sequences in plant genomes using PrimeRoot editors. Nat. Biotechnol. 42, 316–327 (2024).

    CAS  PubMed  Google Scholar 

  92. Dong, O. X. et al. Marker-free carotenoid-enriched rice generated through targeted gene insertion using CRISPR-Cas9. Nat. Commun. 11, 1178 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Lu, Y. et al. A donor-DNA-free CRISPR/Cas-based approach to gene knock-up in rice. Nat. Plants 7, 1445–1452 (2021).

    CAS  PubMed  Google Scholar 

  94. Li, S. et al. Genome-edited powdery mildew resistance in wheat without growth penalties. Nature 602, 455–460 (2022). This study demonstrates the ability to use multiplex genome editing to breed elite wheat germplasm with enhanced disease resistance and increased yields through altering chromatin structure.

    CAS  PubMed  Google Scholar 

  95. Schwartz, C. et al. CRISPR–Cas9-mediated 75.5-Mb inversion in maize. Nat. Plants 6, 1427–1431 (2020).

    CAS  PubMed  Google Scholar 

  96. Rönspies, M. et al. CRISPR/Cas-mediated chromosome engineering: opening up a new avenue for plant breeding. J. Exp. Bot. 72, 177–183 (2021).

    PubMed  Google Scholar 

  97. Rodríguez-Leal, D. et al. Engineering quantitative trait variation for crop improvement by genome editing. Cell 171, 470–480 (2017). This study presents a new approach to regulate gene transcription and explore the biology of quantitative trait loci using CRISPR–Cas9.

    PubMed  Google Scholar 

  98. Xue, C. et al. Tuning plant phenotypes by precise, graded downregulation of gene expression. Nat. Biotechnol. 41, 1758–1764 (2023). This study introduces a new strategy to downregulate protein translation and precisely modulate plant phenotypes by engineering uORFs.

    CAS  PubMed  Google Scholar 

  99. Zhang, H. et al. Genome editing of upstream open reading frames enables translational control in plants. Nat. Biotechnol. 36, 894–898 (2018).

    CAS  PubMed  Google Scholar 

  100. Xing, S. et al. Fine-tuning sugar content in strawberry. Genome Biol. 21, 230 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Song, X. et al. Targeting a gene regulatory element enhances rice grain yield by decoupling panicle number and size. Nat. Biotechnol. 40, 1403–1411 (2022).

    CAS  PubMed  Google Scholar 

  102. Tian, J. et al. Engineering disease-resistant plants with alternative translation efficiency by switching uORF types through CRISPR. Sci. China Life Sci. 67, 1715–1726 (2024).

    CAS  PubMed  Google Scholar 

  103. Kim, N. et al. Deep learning models to predict the editing efficiencies and outcomes of diverse base editors. Nat. Biotechnol. 42, 484–497 (2024).

    CAS  PubMed  Google Scholar 

  104. Yu, G. et al. Prediction of efficiencies for diverse prime editing systems in multiple cell types. Cell 186, 2256–2272 (2023).

    CAS  PubMed  Google Scholar 

  105. Replogle, J. M. et al. Mapping information-rich genotype-phenotype landscapes with genome-scale Perturb-seq. Cell 185, 2559–2575 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Jiang, K. et al. Rapid in silico directed evolution by a protein language model with EVOLVEpro. Science 387, eadr6006 (2024).

    Google Scholar 

  107. He, Y. et al. Protein language models-assisted optimization of a uracil-N-glycosylase variant enables programmable T-to-G and T-to-C base editing. Mol. Cell 84, 1257–1270 (2024).

    CAS  PubMed  Google Scholar 

  108. Huang, J. et al. Discovery of deaminase functions by structure-based protein clustering. Cell 186, 3182–3195 (2023).

    CAS  PubMed  Google Scholar 

  109. Pacesa, M. et al. Past, present, and future of CRISPR genome editing technologies. Cell 187, 1076–1100 (2024).

    CAS  PubMed  Google Scholar 

  110. Wang, J. et al. Scaffolding protein functional sites using deep learning. Science 377, 387–394 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Qu, Y. et al. CRISPR-GPT: an LLM agent for automated design of gene-editing experiments. Preprint at bioRxiv https://doi.org/10.1101/2024.04.25.591003 (2024).

  112. Huang, P. S. et al. The coming of age of de novo protein design. Nature 537, 320–327 (2016).

    CAS  PubMed  Google Scholar 

  113. Bennett, N. R. et al. Atomically accurate de novo design of antibodies with RFdiffusion. Preprint at bioRxiv https://doi.org/10.1101/2024.03.14.585103 (2024). This research proposed a computational design algorithm that can design antibodies to bind user-specified epitopes.

  114. Sesterhenn, F. et al. De novo protein design enables the precise induction of RSV-neutralizing antibodies. Science 368, eaay5051 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  115. Notin, P. et al. Machine learning for functional protein design. Nat. Biotechnol. 42, 216–228 (2024).

    CAS  PubMed  Google Scholar 

  116. Zambaldi, V. et al. De novo design of high-affinity protein binders with AlphaProteo. Preprint at https://doi.org/10.48550/arXiv.2409.08022 (2024).

  117. Baker, D. & Church, G. Protein design meets biosecurity. Science 383, 349 (2024).

    PubMed  Google Scholar 

  118. Yeh, A. H. et al. De novo design of luciferases using deep learning. Nature 614, 774–780 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  119. Wang, J. et al. Protein design using structure-prediction networks: AlphaFold and RoseTTAFold as protein structure foundation models. Cold Spring Harbor Perspect. Biol. 16, a041472 (2024).

    CAS  Google Scholar 

  120. Cao, L. et al. Design of protein-binding proteins from the target structure alone. Nature 605, 551–560 (2022). This study provides a general approach to design protein binders.

    CAS  PubMed  PubMed Central  Google Scholar 

  121. Watson, J. L. et al. De novo design of protein structure and function with RFdiffusion. Nature 620, 1089–1100 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  122. Wu, K. et al. Sequence-specific targeting of intrinsically disordered protein regions. Preprint at bioRxiv https://doi.org/10.1101/2024.07.15.603480 (2024).

  123. Kourelis, J. et al. NLR immune receptor–nanobody fusions confer plant disease resistance. Science 379, 934–939 (2023).

    CAS  PubMed  Google Scholar 

  124. Ortiz, D. et al. Recognition of the Magnaporthe oryzae effector AVR-Pia by the decoy domain of the rice NLR immune receptor RGA5. Plant Cell 29, 156–168 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  125. Yang, J. et al. Enzymatic degradation of deoxynivalenol with the engineered detoxification enzyme Fhb7. JACS Au 4, 619–634 (2024).

    CAS  PubMed  PubMed Central  Google Scholar 

  126. Frank, C. et al. Scalable protein design using optimization in a relaxed sequence space. Science 386, 439–445 (2024).

    CAS  PubMed  PubMed Central  Google Scholar 

  127. Herud-Sikimić, O. et al. A biosensor for the direct visualization of auxin. Nature 592, 768–772 (2021).

    PubMed  PubMed Central  Google Scholar 

  128. Li, W. et al. Tissue-specific accumulation of pH-sensing phosphatidic acid determines plant stress tolerance. Nat. Plants 5, 1012–1021 (2019).

    CAS  PubMed  Google Scholar 

  129. An, L. et al. Binding and sensing diverse small molecules using shape-complementary pseudocycles. Science 385, 276–282 (2024).

    CAS  PubMed  PubMed Central  Google Scholar 

  130. Krishna, R. et al. Generalized biomolecular modeling and design with RoseTTAFold All-Atom. Science 384, eadl2528 (2024). This study develops RoseTTAFold All-Atom and RoseTTAFold diffusion All-Atom, which allow researchers to predict protein–biomolecule complexes and design small molecule binders, respectively.

    CAS  PubMed  Google Scholar 

  131. Lu, L. et al. De novo design of drug-binding proteins with predictable binding energy and specificity. Science 384, 106–112 (2024).

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Horaruang, W. et al. Engineering a K+ channel ‘sensory antenna’ enhances stomatal kinetics, water use efficiency and photosynthesis. Nat. Plants 8, 1262–1274 (2022).

    CAS  PubMed  Google Scholar 

  133. Wang, X. et al. Structural insights into ion selectivity and transport mechanisms of Oryza sativa HKT2;1 and HKT2;2/1 transporters. Nat. Plants 10, 633–644 (2024).

    CAS  PubMed  Google Scholar 

  134. Xu, C. et al. Computational design of transmembrane pores. Nature 585, 129–134 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  135. Scott, A. J. et al. Constructing ion channels from water-soluble α-helical barrels. Nat. Chem. 13, 643–650 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  136. Bi, G. et al. The ZAR1 resistosome is a calcium-permeable channel triggering plant immune signaling. Cell 184, 3528–3541 (2021).

    CAS  PubMed  Google Scholar 

  137. Wang, W. et al. WeiTsing, a pericycle-expressed ion channel, safeguards the stele to confer clubroot resistance. Cell 186, 2656–2671 (2023).

    CAS  PubMed  Google Scholar 

  138. Förderer, A. et al. A wheat resistosome defines common principles of immune receptor channels. Nature 610, 532–539 (2022).

    PubMed  PubMed Central  Google Scholar 

  139. Liu, F. et al. Activation of the helper NRC4 immune receptor forms a hexameric resistosome. Cell 187, 4877–4889 (2024).

    CAS  PubMed  Google Scholar 

  140. Berhanu, S. et al. Sculpting conducting nanopore size and shape through de novo protein design. Science 385, 282–288 (2024).

    CAS  PubMed  PubMed Central  Google Scholar 

  141. Liu, Y. et al. Bottom-up design of calcium channels from defined selectivity filter geometry. Preprint at bioRxiv https://doi.org/10.1101/2024.12.19.629320 (2024).

  142. Zheng, K. et al. ESM All-Atom: multi-scale protein language model for unified molecular modeling. Preprint at https://doi.org/10.48550/arXiv.2403.12995 (2024).

  143. Collins, A. S. P. et al. Parallel, continuous monitoring and quantification of programmed cell death in plant tissue. Adv. Sci. 11, 2400225 (2024).

    CAS  Google Scholar 

  144. Borowsky, A. T. & Bailey-Serres, J. Rewiring gene circuitry for plant improvement. Nat. Genet. 56, 1574–1582 (2024).

    CAS  PubMed  Google Scholar 

  145. Oliva, R. et al. Broad-spectrum resistance to bacterial blight in rice using genome editing. Nat. Biotechnol. 37, 1344–1350 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  146. Chen, Z. et al. De novo design of protein logic gates. Science 368, 78–84 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  147. Rui, Z. et al. High-throughput proximal ground crop phenotyping systems—a comprehensive review. Comput. Electron. Agric. 224, 109108 (2024).

    Google Scholar 

  148. Li, G. et al. The sequences of 1504 mutants in the model rice variety Kitaake facilitate rapid functional genomic studies. Plant Cell 29, 1218–1231 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  149. Lynch, J. P. Harnessing root architecture to address global challenges. Plant J. 109, 415–431 (2022).

    CAS  PubMed  Google Scholar 

  150. Scharwies, J. D. et al. Moisture-responsive root-branching pathways identified in diverse maize breeding germplasm. Science 387, 666–673 (2025).

    CAS  PubMed  PubMed Central  Google Scholar 

  151. Shi, X. et al. Ultra-wideband microwave imaging system for root phenotyping. Sensors 22, 2031 (2022).

    PubMed  PubMed Central  Google Scholar 

  152. Nagel, K. A. et al. GROWSCREEN-Rhizo is a novel phenotyping robot enabling simultaneous measurements of root and shoot growth for plants grown in soil-filled rhizotrons. Funct. Plant Biol. 39, 891–904 (2012).

    PubMed  Google Scholar 

  153. Yu, P. et al. Seedling root system adaptation to water availability during maize domestication and global expansion. Nat. Genet. 56, 1245–1256 (2024). This study reveals that reshaping maize root architecture by reducing the seed root number and increasing lateral root density enhances drought resilience.

    CAS  PubMed  Google Scholar 

  154. Huang, X. et al. Genome-wide association studies of 14 agronomic traits in rice landraces. Nat. Genet. 42, 961–967 (2010).

    CAS  PubMed  Google Scholar 

  155. Wu, X. et al. Using high-throughput multiple optical phenotyping to decipher the genetic architecture of maize drought tolerance. Genome Biol. 22, 185 (2021). This study utilized a HTP system to extract drought tolerance phenotypes in maize and employed genetic methods such as GWAS in the identification of genes controlling drought resistance in maize.

    CAS  PubMed  PubMed Central  Google Scholar 

  156. Al-Tamimi, N. et al. Salinity tolerance loci revealed in rice using high-throughput non-invasive phenotyping. Nat. Commun. 7, 13342 (2016). This work uses HTP and GWAS to study salt tolerance in rice, thereby gaining a deeper understanding of the early response of rice to salinity.

    PubMed  PubMed Central  Google Scholar 

  157. Gao, J. et al. Deciphering genetic basis of developmental and agronomic traits by integrating high-throughput optical phenotyping and genome-wide association studies in wheat. Plant Biotechnol. J. 21, 1966–1977 (2023).

    PubMed  PubMed Central  Google Scholar 

  158. Li, B. et al. Phenomics-based GWAS analysis reveals the genetic architecture for drought resistance in cotton. Plant Biotechnol. J. 18, 2533–2544 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  159. Morton, M. et al. Deciphering salt stress responses in Solanum pimpinellifolium through high-throughput phenotyping. Plant J. 119, 2514–2537 (2024).

    CAS  PubMed  Google Scholar 

  160. Wang, W. et al. Integration of high-throughput phenotyping, GWAS, and predictive models reveals the genetic architecture of plant height in maize. Mol. Plant 16, 354–373 (2023).

    CAS  PubMed  Google Scholar 

  161. Crain, J. et al. Combining high-throughput phenotyping and genomic information to increase prediction and selection accuracy in wheat breeding. Plant Genome 11, 170043 (2018).

    Google Scholar 

  162. Lane, H. M. et al. Phenomic selection and prediction of maize grain yield from near-infrared reflectance spectroscopy of kernels. Plant Phenome J. 3, e20002 (2020).

    Google Scholar 

  163. Tross, M. C. et al. Data driven discovery and quantification of hyperspectral leaf reflectance phenotypes across a maize diversity panel. Plant Phenome J. 7, e20106 (2024).

    Google Scholar 

  164. Rincent, R. et al. Phenomic selection is a low-cost and high-throughput method based on indirect predictions: proof of concept on wheat and poplar. G3 8, 3961–3972 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  165. Gibbs, J. A. et al. Active vision and surface reconstruction for 3D plant shoot modelling. IEEE/ACM Trans. Comput. Biol. Bioinformatics 17, 1907–1917 (2020).

    Google Scholar 

  166. Jin, S. et al. Lidar sheds new light on plant phenomics for plant breeding and management: recent advances and future prospects. ISPRS 171, 202–223 (2021).

    Google Scholar 

  167. Wagner, R. et al. Imagine all the plants: evaluation of a light-field camera for on-site crop growth monitoring. Remote Sens. 8, 823 (2016).

    Google Scholar 

  168. Chang, J. et al. EI-MVSNet: epipolar-guided multi-view stereo network with interval-aware label. IEEE Trans. Image Process. 33, 753–766 (2024).

    PubMed  Google Scholar 

  169. Gu, Y. et al. Novel 3D photosynthetic traits derived from the fusion of UAV LiDAR point cloud and multispectral imagery in wheat. Remote Sens. Environ. 311, 114244 (2024).

    Google Scholar 

  170. Zhang, Y. et al. Dissecting the phenotypic components and genetic architecture of maize stem vascular bundles using high-throughput phenotypic analysis. Plant Biotechnol. J. 19, 35–50 (2021).

    CAS  PubMed  Google Scholar 

  171. Zhang, Y. et al. Plant microphenotype: from innovative imaging to computational analysis. Plant Biotechnol. J. 22, 802–818 (2024).

    PubMed  PubMed Central  Google Scholar 

  172. Liu, Z. et al. Sustained deep-tissue voltage recording using a fast indicator evolved for two-photon microscopy. Cell 185, 3408–3425 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  173. Ovečka, M. et al. Multiscale imaging of plant development by light-sheet fluorescence microscopy. Nat. Plants 4, 639–650 (2018). This work shows that light-sheet fluorescence microscopy methods collectively represent a major breakthrough in the development of bio-imaging of living multicellular organisms.

    PubMed  Google Scholar 

  174. Payne, W. Z. & Kurouski, D. Raman spectroscopy enables phenotyping and assessment of nutrition values of plants: a review. Plant Methods 17, 78 (2021).

    PubMed  PubMed Central  Google Scholar 

  175. Gonçalves, M. T. V. et al. Near-infrared spectroscopy outperforms genomics for predicting sugarcane feedstock quality traits. PLoS ONE 16, e0236853 (2021).

    PubMed  PubMed Central  Google Scholar 

  176. Sineshchekov, V. A. Applications of fluorescence spectroscopy in the investigation of plant phytochrome invivo. Plant Physiol. Biochem. 208, 108434 (2024).

    CAS  PubMed  Google Scholar 

  177. Barnes, M. et al. Fourier transform infrared spectroscopy as a non-destructive method for analysing herbarium specimens. Biol. Lett. 19, 20220546 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  178. Hacisalihoglu, G. & Armstrong, P. Crop seed phenomics: focus on non-destructive functional trait phenotyping methods and applications. Plants 12, 1177 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  179. Kou, T. et al. Terahertz spectroscopy for accurate identification of Panax quinquefolium basing on nonconjugated 24(R)-pseudoginsenoside F11. Plant Phenomics 2021, 6793457 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  180. Horn, P. J. & Chapman, K. D. Imaging plant metabolism in situ. J. Exp. Bot. 75, 1654–1670 (2024).

    CAS  PubMed  Google Scholar 

  181. Song, P. et al. High-throughput phenotyping: breaking through the bottleneck in future crop breeding. Crop J. 9, 633–645 (2021).

    Google Scholar 

  182. Wen, W. et al. Standard framework construction of technology and equipment for big data in crop phenomics. Engineering 42, 175–184 (2024).

    Google Scholar 

  183. Teng, Z. et al. Panicle-Cloud: an open and AI-powered cloud computing platform for quantifying rice panicles from drone-collected imagery to enable the classification of yield production in rice. Plant Phenomics 5, 0105 (2023).

    PubMed  PubMed Central  Google Scholar 

  184. Wei, X. et al. A quantitative genomics map of rice provides genetic insights and guides breeding. Nat. Genet. 53, 243–253 (2021).

    CAS  PubMed  Google Scholar 

  185. Zhang, J. et al. Engineering rice genomes towards green super rice. Curr. Opin. Plant Biol. 82, 102664 (2024).

    CAS  PubMed  Google Scholar 

  186. Moor, M. et al. Foundation models for generalist medical artificial intelligence. Nature 616, 259–265 (2023).

    CAS  PubMed  Google Scholar 

  187. Zhang, K. et al. A generalist vision–language foundation model for diverse biomedical tasks. Nat. Med. 30, 3129–3141 (2024).

    CAS  PubMed  Google Scholar 

  188. Zhu, W. et al. The CropGPT project: call for a global, coordinated effort in precision design breeding driven by AI using biological big data. Mol. Plant 17, 215–218 (2024).

    CAS  PubMed  Google Scholar 

  189. Sharma, S. et al. DeepG2P: fusing multi-modal data to improve crop production. Preprint at https://doi.org/10.48550/arXiv.2211.05986 (2022).

  190. Wang, H. et al. Horizontal gene transfer of Fhb7 from fungus underlies Fusarium head blight resistance in wheat. Science 368, eaba5435 (2020).

    CAS  PubMed  Google Scholar 

  191. Zhang, C. et al. High-resolution satellite imagery applications in crop phenotyping: an overview. Comput. Electron. Agric. 175, 105584 (2020).

    Google Scholar 

  192. Jiang, Z. et al. Combining UAV-RGB high-throughput field phenotyping and genome-wide association study to reveal genetic variation of rice germplasms in dynamic response to drought stress. New Phytol. 232, 440–455 (2021).

    CAS  PubMed  Google Scholar 

  193. Lu, S. et al. Natural variation at the soybean J locus improves adaptation to the tropics and enhances yield. Nat. Genet. 49, 773–779 (2017).

    CAS  PubMed  Google Scholar 

  194. Qi, X. et al. Genome editing enables next-generation hybrid seed production technology. Mol. Plant 13, 1262–1269 (2020).

    CAS  PubMed  Google Scholar 

  195. Wang, J. et al. A single transcription factor promotes both yield and immunity in rice. Science 361, 1026–1028 (2018).

    CAS  PubMed  Google Scholar 

  196. Xu, K. et al. Sub1A is an ethylene-response-factor-like gene that confers submergence tolerance to rice. Nature 442, 705–708 (2006).

    CAS  PubMed  Google Scholar 

  197. Ristaino, J. B. et al. The persistent threat of emerging plant disease pandemics to global food security. Proc. Natl Acad. Sci. USA 118, e2022239118 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  198. Xia, K. et al. The single-cell stereo-seq reveals region-specific cell subtypes and transcriptome profiling in Arabidopsis leaves. Dev. Cell 57, 1299–1310 (2022).

    CAS  PubMed  Google Scholar 

  199. Sun, G. et al. The maize single-nucleus transcriptome comprehensively describes signaling networks governing movement and development of grass stomata. Plant Cell 34, 1890–1911 (2022).

    PubMed  PubMed Central  Google Scholar 

  200. Ye, H. et al. A novel in vivo genome editing doubled haploid system for Zea mays L. Nat. Plants 10, 1493–1501 (2024).

    CAS  PubMed  Google Scholar 

  201. Watson, A. et al. Speed breeding is a powerful tool to accelerate crop research and breeding. Nat. Plants 4, 23–29 (2018).

    PubMed  Google Scholar 

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Acknowledgements

We thank G. Lawrence, D. Llewellyn, H. Puchta, F. Lu, P. Lu, J. Luo, R. McIntosh, R. Milne, W. Qian, B. Wang, X. J. Wang, X. W. Wang, F. Zhao and K. T. Zhao for their discussions and critical reading of the manuscript and members of the Li and Gao laboratories for assistance with figures and references. Research in the authors’ laboratories was supported by the following grants: Biological Breeding-National Science and Technology Major Project (2023ZD04070) to G.L.; National Key Research and Development Program (2022YFF1002802 to C.G. and 2022YFA1304402 to G.L.); Key R&D Program of Hubei Province (2023BBB171), National Natural Science Foundation of China (32172373) and Fundamental Research Funds for the Central Universities (2662023PY006, AML2023A05, 2662025ZKPY008 and 2662024ZKPY001) to G.L.; Audacious GC4 (PG117880) for Smart Therapeutics to L.A.; NSFC (32388201); the Ministry of Agriculture and Rural Affairs of China and the New Cornerstone Science Foundation to C.G.; NNSFC (U21A20205), Key Agricultural Core Technology Research Project in Hubei Province (HBNYHXGG2023-9) and FRFCU (2662024ZKPY003) to W.Y.; China National GeneBank (CNGB) to T.W.; Biotechnology and Biological Sciences Research Council (BBS/E/IB/23001 and BBS/E/W/0012843) and Engineering and Physical Sciences Research Council (EP/Y005430/1) to J.H.D.; NNSFC (32293243) to K.X.; the Bill and Melinda Gates Foundation (INV-004428) to E.S.L.; KAUST Baseline and Competitive Research Grants (9 and 10) to R.A.W. This work was also supported by Hubei Hongshan Laboratory.

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G.L., L.A., W.Y., L.Y. and C.G. conceived the study and were responsible for the overall frame of the Review. G.L., L.A., W.Y., L.Y., T.W., J.S., J.W., J.H.D., K.X., A.R.F., E.S.L., R.A.W. and C.G. contributed to the design and writing of the manuscript. G.L., L.A., W.Y., L.Y., J.S., J.W. and C.G. conceptualized and drafted the figures. All authors revised the work, provided critical feedback and approved the final version.

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Correspondence to Guotian Li or Caixia Gao.

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Supplementary Table 1

High throughput phenotyping method and application in crop improvement.

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Li, G., An, L., Yang, W. et al. Integrated biotechnological and AI innovations for crop improvement. Nature 643, 925–937 (2025). https://doi.org/10.1038/s41586-025-09122-8

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