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A Cell Observatory to reveal the subcellular foundations of life

Imaging the 4D choreography of subcellular events in living multicellular organisms at high spatiotemporal resolution could reveal life’s fundamental principles. Yet extracting these principles from petabyte-scale image data requires fusing advanced light microscopy and cutting-edge machine learning models with biological insight and expertise.

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Fig. 1: From imaging to understanding: AI as a tool to unravel the complexity of living systems.

References

  1. Prakash, K., Diederich, B., Heintzmann, R. & Schermelleh, L. Philos. Trans. Roy. Soc. Math. Phys. Eng. Sci. 380, 20210110 (2022).

    Google Scholar 

  2. Stelzer, E. H. K. et al. Nat. Revs. Methods Primers 1, 73 (2021).

    Article  CAS  Google Scholar 

  3. Zalejski, J., Sun, J. & Sharma, A. J. Imaging 9, 192 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Chong, S. et al. Science 361, 378 (2018).

    Article  CAS  Google Scholar 

  5. Chen, B.-C. et al. Science 346, 1257998 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Liu, T.-L. et al. Science 360, eaaq1392 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  7. Ruan, X. et al. Preprint at bioRxiv https://doi.org/10.1101/2023.12.31.573734 (2024).

  8. Schneider, E., Robertson, B., Kuhn, A., Lux, C. & Nienhaus, M. Parallel Comput. 107, 102809 (2021).

    Article  Google Scholar 

  9. Wolny, A. et al. eLife 9, e57613 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Vaswani, A. et al. Preprint at arXiv https://arxiv.org/abs/1706.03762 (2017).

  11. Dosovitskiy, A. et al. In International Conference on Learning Representations Conference Proceedings (2021); https://openreview.net/pdf?id=YicbFdNTTy

  12. Kirillov, A. et al. Preprint at arXiv https://doi.org/10.48550/arXiv.2304.02643 (2023).

  13. Weissman, T. A. & Pan, Y. A. Genetics 199, 293–306 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  14. Zhanghao, K. et al. Preprint at ResearchSquare https://doi.org/10.21203/rs.3.rs-1686675/v1 (2022).

  15. Li, Z., Zhang, Y., Wu, J. & Dai, Q. Nat. Methods 20, 958–961 (2023).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

I am very grateful for the many colleagues who critiqued and help hone this Comment, but I am particularly indebted to Gokul Upadhyayula, assistant professor and director of the Advanced Bioimaging Center (ABC) at UC Berkeley, for visionary discussions and for his patience in teaching this old dog some new tricks. E.B. is funded by the Howard Hughes Medical Institute (HHMI) with additional support from the Eugene D. Commins Chair in Experimental Physics at UC Berkeley. Additional funding for the ABC comes from the Philomathia Foundation.

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Correspondence to Eric Betzig.

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E.B. is inventor or co-inventor of the following relevant US patents: patents 7,894,136, 8,711,211 and 9,477,074, licensed to Carl Zeiss Microscopy; and patents 9,500,846 and 10,051,240, assigned to HHMI. E.B. is also a cofounder of Eikon Therapeutics.

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Nature Methods thanks Philip Hockberger and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Betzig, E. A Cell Observatory to reveal the subcellular foundations of life. Nat Methods (2024). https://doi.org/10.1038/s41592-024-02379-3

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