How to build the virtual cell with artificial intelligence: Priorities and opportunities

Charlotte Bunne; Yusuf Roohani; Yanay Rosen; Ankit Gupta; Xikun Zhang; Marcel Roed; Theo Alexandrov; Mohammed AlQuraishi; Patricia Brennan; Daniel B Burkhardt; Andrea Califano; Jonah Cool; Abby F Dernburg; Kirsty Ewing; Emily B Fox; Matthias Haury; Amy E Herr; Eric Horvitz; Patrick D Hsu; Viren Jain; Gregory R Johnson; Thomas Kalil; David R Kelley; Shana O Kelley; Anna Kreshuk; Tim Mitchison; Stephani Otte; Jay Shendure; Nicholas J Sofroniew; Fabian Theis; Christina V Theodoris; Srigokul Upadhyayula; Marc Valer; Bo Wang; Eric Xing; Serena Yeung-Levy; Marinka Zitnik; Theofanis Karaletsos; Aviv Regev; Emma Lundberg; Jure Leskovec; Stephen R Quake

doi:10.1016/j.cell.2024.11.015

How to build the virtual cell with artificial intelligence: Priorities and opportunities

Cell. 2024 Dec 12;187(25):7045-7063. doi: 10.1016/j.cell.2024.11.015.

Authors

Charlotte Bunne¹, Yusuf Roohani², Yanay Rosen³, Ankit Gupta⁴, Xikun Zhang⁵, Marcel Roed³, Theo Alexandrov⁶, Mohammed AlQuraishi⁷, Patricia Brennan⁸, Daniel B Burkhardt⁹, Andrea Califano¹⁰, Jonah Cool⁸, Abby F Dernburg¹¹, Kirsty Ewing⁸, Emily B Fox¹², Matthias Haury¹³, Amy E Herr¹⁴, Eric Horvitz¹⁵, Patrick D Hsu¹⁶, Viren Jain¹⁷, Gregory R Johnson¹⁸, Thomas Kalil¹⁹, David R Kelley²⁰, Shana O Kelley²¹, Anna Kreshuk²², Tim Mitchison²³, Stephani Otte¹³, Jay Shendure²⁴, Nicholas J Sofroniew²⁵, Fabian Theis²⁶, Christina V Theodoris²⁷, Srigokul Upadhyayula²⁸, Marc Valer⁸, Bo Wang²⁹, Eric Xing³⁰, Serena Yeung-Levy³¹, Marinka Zitnik³², Theofanis Karaletsos³³, Aviv Regev³⁴, Emma Lundberg³⁵, Jure Leskovec³⁶, Stephen R Quake³⁷

Affiliations

¹ Department of Computer Science, Stanford University, Stanford, CA, USA; Genentech, South San Francisco, CA, USA; Chan Zuckerberg Initiative, Redwood City, CA, USA; School of Computer and Communication Sciences and School of Life Sciences, EPFL, Lausanne, Switzerland.
² Department of Computer Science, Stanford University, Stanford, CA, USA; Chan Zuckerberg Initiative, Redwood City, CA, USA; Arc Institute, Palo Alto, CA, USA.
³ Department of Computer Science, Stanford University, Stanford, CA, USA; Chan Zuckerberg Initiative, Redwood City, CA, USA.
⁴ Chan Zuckerberg Initiative, Redwood City, CA, USA; Department of Protein Science, Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden.
⁵ Department of Computer Science, Stanford University, Stanford, CA, USA; Chan Zuckerberg Initiative, Redwood City, CA, USA; Department of Bioengineering, Stanford University, Stanford, CA, USA.
⁶ Department of Pharmacology, University of California, San Diego, San Diego, CA, USA; Department of Bioengineering, University of California, San Diego, San Diego, CA, USA.
⁷ Department of Bioengineering, University of California, San Diego, San Diego, CA, USA.
⁸ Chan Zuckerberg Initiative, Redwood City, CA, USA.
⁹ Cellarity, Somerville, MA, USA.
¹⁰ Department of Systems Biology, Columbia University, New York, NY, USA; Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA; Chan Zuckerberg Biohub, New York, NY, USA.
¹¹ Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
¹² Department of Computer Science, Stanford University, Stanford, CA, USA; Department of Statistics, Stanford University, Stanford, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA, USA.
¹³ Chan Zuckerberg Institute for Advanced Biological Imaging, Redwood City, CA, USA.
¹⁴ Chan Zuckerberg Biohub, San Francisco, CA, USA; Department of Bioengineering, University of California, Berkeley, Berkeley, CA, USA.
¹⁵ Microsoft Research, Redmond, WA, USA.
¹⁶ Arc Institute, Palo Alto, CA, USA; Department of Bioengineering, University of California, Berkeley, Berkeley, CA, USA; Center for Computational Biology, University of California, Berkeley, Berkeley, CA, USA.
¹⁷ Google Research, Mountain View, CA, USA.
¹⁸ NewLimit, San Francisco, CA, USA.
¹⁹ Schmidt Futures, New York, NY, USA.
²⁰ Calico Life Sciences LLC, San Francisco, CA, USA.
²¹ Chan Zuckerberg Biohub, Chicago, IL, USA; Northwestern University, Evanston, IL, USA.
²² Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
²³ Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
²⁴ Department of Genome Sciences, University of Washington, Seattle, WA, USA; Brotman Baty Institute for Precision Medicine, Seattle, WA, USA; Seattle Hub for Synthetic Biology, Seattle, WA, USA; Howard Hughes Medical Institute, Seattle, WA, USA.
²⁵ EvolutionaryScale, PBC, New York, NY, USA.
²⁶ Institute of Computational Biology, Helmholtz Center Munich, Munich, Germany; School of Computing, Information and Technology, Technical University of Munich, Munich, Germany; TUM School of Life Sciences Weihenstephan, Technical University of Munich, Munich, Germany.
²⁷ Gladstone Institute of Cardiovascular Disease, Gladstone Institute of Data Science and Biotechnology, San Francisco, CA, USA; Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA.
²⁸ Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA, USA; Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
²⁹ Department of Computer Science, University of Toronto, Toronto, ON, Canada; Vector Institute, Toronto, ON, Canada.
³⁰ Carnegie Mellon University, School of Computer Science, Pittsburgh, PA, USA; Mohamed Bin Zayed University of Artificial Intelligence, Abu Dhabi, United Arab Emirates.
³¹ Department of Computer Science, Stanford University, Stanford, CA, USA; Department of Biomedical Data Science, Stanford University, Stanford, CA, USA.
³² Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA; Kempner Institute for the Study of Natural and Artificial Intelligence, Harvard University, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
³³ Chan Zuckerberg Initiative, Redwood City, CA, USA. Electronic address: [email protected].
³⁴ Genentech, South San Francisco, CA, USA. Electronic address: [email protected].
³⁵ Chan Zuckerberg Initiative, Redwood City, CA, USA; Department of Protein Science, Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden; Department of Bioengineering, Stanford University, Stanford, CA, USA; Department of Pathology, Stanford University, Stanford, CA, USA. Electronic address: [email protected].
³⁶ Department of Computer Science, Stanford University, Stanford, CA, USA; Chan Zuckerberg Initiative, Redwood City, CA, USA. Electronic address: [email protected].
³⁷ Chan Zuckerberg Initiative, Redwood City, CA, USA; Department of Bioengineering, Stanford University, Stanford, CA, USA; Department of Applied Physics, Stanford University, Stanford, CA, USA. Electronic address: [email protected].

PMID: 39672099
DOI: 10.1016/j.cell.2024.11.015

Abstract

Cells are essential to understanding health and disease, yet traditional models fall short of modeling and simulating their function and behavior. Advances in AI and omics offer groundbreaking opportunities to create an AI virtual cell (AIVC), a multi-scale, multi-modal large-neural-network-based model that can represent and simulate the behavior of molecules, cells, and tissues across diverse states. This Perspective provides a vision on their design and how collaborative efforts to build AIVCs will transform biological research by allowing high-fidelity simulations, accelerating discoveries, and guiding experimental studies, offering new opportunities for understanding cellular functions and fostering interdisciplinary collaborations in open science.

Keywords: AI; ML; cell biology; virtual cell.

Publication types

Review

MeSH terms

Animals
Artificial Intelligence*
Computer Simulation
Humans
Models, Biological
Neural Networks, Computer