Dataset Information

A genome-wide atlas of co-essential modules assigns function to uncharacterized genes

ABSTRACT: A central remaining question in the post-genomic era is how genes interact to form biological pathways. Measurements of gene dependency across hundreds of cell lines have been used to cluster genes into ‘co-essential’ pathways, but this approach has been limited by ubiquitous false positives. Here, we develop a statistical method that enables robust identification of gene co-essentiality and yields a genome-wide set of functional modules. This atlas recapitulates diverse pathways and protein complexes and predicts the functions of 155 uncharacterized genes. Validating top predictions, we show that TMEM189 encodes plasmanylethanolamine desaturase, the long-sought key enzyme for plasmalogen synthesis. We also show that C15orf57 binds the AP2 complex, localizes to clathrin-coated pits, and enables efficient transferrin uptake. Finally, we provide an interactive web tool for the community to explore our results. Our results establish co-essentiality profiling as a powerful resource for biological pathway identification and discovery of novel gene functions.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

DISEASE(S): Cervix Carcinoma

SUBMITTER: Roarke Kamber

LAB HEAD: Michael Bassik

PROVIDER: PXD023558 | Pride | 2022-02-16

REPOSITORIES: Pride

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			Action	DRS
	Lumos2_Roarke_080118.pdResult	Other
	Lumos2_Roarke_080118.raw	Raw

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Publications

A genome-wide atlas of co-essential modules assigns function to uncharacterized genes.

Wainberg Michael M Kamber Roarke A RA Balsubramani Akshay A Meyers Robin M RM Sinnott-Armstrong Nasa N Hornburg Daniel D Jiang Lihua L Chan Joanne J Jian Ruiqi R Gu Mingxin M Shcherbina Anna A Dubreuil Michael M MM Spees Kaitlyn K Meuleman Wouter W Snyder Michael P MP Bassik Michael C MC Kundaje Anshul A

Nature genetics 20210415 5

A central question in the post-genomic era is how genes interact to form biological pathways. Measurements of gene dependency across hundreds of cell lines have been used to cluster genes into 'co-essential' pathways, but this approach has been limited by ubiquitous false positives. In the present study, we develop a statistical method that enables robust identification of gene co-essentiality and yields a genome-wide set of functional modules. This atlas recapitulates diverse pathways and prote ...[more]

PMID: 33859415

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