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Functional unknomics: closing the knowledge gap to accelerate biomedical research

Joao Rocha, Satish Arcot Jayaram, Tim J. Stevens, Nadine Muschalik, Rajen D. Shah, Sahar Emran, Cristina Robles, Matthew Freeman, Sean Munro
doi: https://doi.org/10.1101/2022.06.28.497983
Joao Rocha
1MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK
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Satish Arcot Jayaram
1MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK
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Tim J. Stevens
1MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK
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Nadine Muschalik
1MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK
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Rajen D. Shah
2Centre for Mathematical Sciences, University of Cambridge, Cambridge CB3 0WB
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Sahar Emran
1MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK
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Cristina Robles
1MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK
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Matthew Freeman
1MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK
3Dunn School of Pathology, University of Oxford, Oxford OX1 3RE
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  • For correspondence: sean@mrc-lmb.cam.ac.uk matthew.freeman@path.ox.ac.uk
Sean Munro
1MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK
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  • For correspondence: sean@mrc-lmb.cam.ac.uk matthew.freeman@path.ox.ac.uk
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Summary

The human genome encodes ∼20,000 proteins, many still uncharacterised. Scientific and social factors have resulted in a focus on well-studied proteins, leading to a concern that poorly understood genes are unjustifiably neglected. To address this, we have developed an “Unknome database” that ranks proteins based on how little is known about them. We applied RNAi in Drosophila to 260 unknown genes that are conserved between flies and humans. About a quarter are required for viability, and functional screening of the rest revealed hits for fertility, development, locomotion, protein quality control and resilience to stress. CRISPR/Cas9 gene disruption validated a component of Notch signalling and two genes contributing to male fertility. Our work demonstrates the importance of poorly understood genes, provides a resource for future research acceleration, and highlights a need for our awareness of ignorance to be protected from erosion by automated database annotation.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted June 28, 2022.
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Functional unknomics: closing the knowledge gap to accelerate biomedical research
Joao Rocha, Satish Arcot Jayaram, Tim J. Stevens, Nadine Muschalik, Rajen D. Shah, Sahar Emran, Cristina Robles, Matthew Freeman, Sean Munro
bioRxiv 2022.06.28.497983; doi: https://doi.org/10.1101/2022.06.28.497983
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Functional unknomics: closing the knowledge gap to accelerate biomedical research
Joao Rocha, Satish Arcot Jayaram, Tim J. Stevens, Nadine Muschalik, Rajen D. Shah, Sahar Emran, Cristina Robles, Matthew Freeman, Sean Munro
bioRxiv 2022.06.28.497983; doi: https://doi.org/10.1101/2022.06.28.497983

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