RT Journal Article
SR Electronic
T1 Functional unknomics: closing the knowledge gap to accelerate biomedical research
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.06.28.497983
DO 10.1101/2022.06.28.497983
A1 Joao Rocha
A1 Satish Arcot Jayaram
A1 Tim J. Stevens
A1 Nadine Muschalik
A1 Rajen D. Shah
A1 Sahar Emran
A1 Cristina Robles
A1 Matthew Freeman
A1 Sean Munro
YR 2022
UL http://biorxiv.org/content/early/2022/06/28/2022.06.28.497983.abstract
AB 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 StatementThe authors have declared no competing interest.