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dc.contributor.author Diss, Guillaume
dc.contributor.author Lehner, Ben, 1978-
dc.date.accessioned 2019-11-13T11:18:54Z
dc.date.available 2019-11-13T11:18:54Z
dc.date.issued 2018
dc.identifier.citation Diss G, Lehner B. The genetic landscape of a physical interaction. eLife. 2018;7:e32472. DOI: 10.7554/eLife.32472
dc.identifier.issn 2050-084X
dc.identifier.uri http://hdl.handle.net/10230/42840
dc.description.abstract A key question in human genetics and evolutionary biology is how mutations in different genes combine to alter phenotypes. Efforts to systematically map genetic interactions have mostly made use of gene deletions. However, most genetic variation consists of point mutations of diverse and difficult to predict effects. Here, by developing a new sequencing-based protein interaction assay - deepPCA - we quantified the effects of >120,000 pairs of point mutations on the formation of the AP-1 transcription factor complex between the products of the FOS and JUN proto-oncogenes. Genetic interactions are abundant both in cis (within one protein) and trans (between the two molecules) and consist of two classes - interactions driven by thermodynamics that can be predicted using a three-parameter global model, and structural interactions between proximally located residues. These results reveal how physical interactions generate quantitatively predictable genetic interactions.
dc.description.sponsorship This work was supported by a European Research Council (ERC) Consolidator grant (616434), the Spanish Ministry of Economy and Competitiveness (BFU2011-26206 and ‘Centro de Excelencia Severo Ochoa' SEV-2012–0208), the AXA Research Fund, the Bettencourt Schueller Foundation, Agencia de Gestio d’Ajuts Universitaris i de Recerca (AGAUR, SGR-831), the EMBL-CRG Systems Biology Program, and the CERCA Program/Generalitat de Catalunya. GD is a non-stipendiary EMBO Fellow and a Marie-Curie Fellow under grant agreement 608959.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher eLife
dc.relation.ispartof eLife. 2018;7:e32472
dc.rights © 2018, Diss et al. This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use and redistribution provided that the original author and source are credited.
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title The genetic landscape of a physical interaction
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.7554/eLife.32472
dc.subject.keyword S. cerevisiae
dc.subject.keyword Computational biology
dc.subject.keyword Deep mutagenesis
dc.subject.keyword Epistasis
dc.subject.keyword Genetic interaction
dc.subject.keyword Human
dc.subject.keyword Protein interactions
dc.subject.keyword Systems biology
dc.subject.keyword Transcription factors
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/616434
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2011-26206
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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