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Functional genomic hypothesis generation and experimentation by a robot scientist

Abstract

The question of whether it is possible to automate the scientific process is of both great theoretical interest1,2 and increasing practical importance because, in many scientific areas, data are being generated much faster than they can be effectively analysed. We describe a physically implemented robotic system that applies techniques from artificial intelligence3,4,5,6,7,8 to carry out cycles of scientific experimentation. The system automatically originates hypotheses to explain observations, devises experiments to test these hypotheses, physically runs the experiments using a laboratory robot, interprets the results to falsify hypotheses inconsistent with the data, and then repeats the cycle. Here we apply the system to the determination of gene function using deletion mutants of yeast (Saccharomyces cerevisiae) and auxotrophic growth experiments9. We built and tested a detailed logical model (involving genes, proteins and metabolites) of the aromatic amino acid synthesis pathway. In biological experiments that automatically reconstruct parts of this model, we show that an intelligent experiment selection strategy is competitive with human performance and significantly outperforms, with a cost decrease of 3-fold and 100-fold (respectively), both cheapest and random-experiment selection.

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Figure 1
Figure 2: A schematic representation of the logical model of the aromatic amino acid pathway in yeast.
Figure 3: Actual and simulated performance of the Robot Scientist.

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Acknowledgements

We thank D. Page, U. Sarkans, A. Tamaddoni, M. Sternberg, A. Sloman and D. Michie for their help and advice, and D. Struttman for technical assistance. The work was funded by the BBSRC, the EPSRC, the Wellcome Trust and PharmDM.

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Correspondence to Stephen G. Oliver.

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R.D.K. is a co-founder and member of the scientific board of PharmaDM, Kapeldreef 60, B-3001 Heverlee, Belgium.

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King, R., Whelan, K., Jones, F. et al. Functional genomic hypothesis generation and experimentation by a robot scientist. Nature 427, 247–252 (2004). https://doi.org/10.1038/nature02236

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