RT Journal Article
SR Electronic
T1 Reconstructing regulatory pathways by systematically mapping protein localization interdependency networks
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 116749
DO 10.1101/116749
A1 James Dodgson
A1 Anatole Chessel
A1 Federico Vaggi
A1 Marco Giordan
A1 Miki Yamamoto
A1 Kunio Arai
A1 Marisa Madrid
A1 Marco Geymonat
A1 Juan Francisco Abenza
A1 José Cansado
A1 Masamitsu Sato
A1 Attila Csikasz-Nagy
A1 Rafael Edgardo Carazo Salas
YR 2017
UL http://biorxiv.org/content/early/2017/03/14/116749.abstract
AB A key goal of functional genomics is to elucidate how genes and proteins act together in space and time, wired as pathways, to control specific aspects of cell biological function. Here, we develop a method to quantitatively determine proteins’ localization interdependencies at high throughput. We show that this method can be used to systematically obtain weighted, signed and directional pathway relationships, and hence to reconstruct a detailed pathway wiring. As proof-of-principle, we focus on 42 factors that control cell polarity in fission yeast (Schizosaccharomyces pombe) and use high-throughput confocal microscopy and quantitative image analysis to reconstruct their Localization Interdependency Network (LIN). Through this approach we identify 554 pairwise interactions across the factors, including 98% putative new directed links. Validation of an unexpected interaction between two polarity factor subgroups - the polarity landmark proteins and the cell integrity pathway components - by orthogonal phenotyping demonstrates the power of the LIN approach in detecting subtle, systems-level causal connections.