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Modularity and directionality in genetic interaction maps

Motivation: Genetic interactions between genes reflect functional relationships caused by a wide range of molecular mechanisms. Large-scale genetic interaction assays lead to a wealth of information about the functional relations between genes. However, the vast number of observed interactions, alon...

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Autores principales: Jaimovich, Ariel, Rinott, Ruty, Schuldiner, Maya, Margalit, Hanah, Friedman, Nir
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2881382/
https://www.ncbi.nlm.nih.gov/pubmed/20529911
http://dx.doi.org/10.1093/bioinformatics/btq197
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author Jaimovich, Ariel
Rinott, Ruty
Schuldiner, Maya
Margalit, Hanah
Friedman, Nir
author_facet Jaimovich, Ariel
Rinott, Ruty
Schuldiner, Maya
Margalit, Hanah
Friedman, Nir
author_sort Jaimovich, Ariel
collection PubMed
description Motivation: Genetic interactions between genes reflect functional relationships caused by a wide range of molecular mechanisms. Large-scale genetic interaction assays lead to a wealth of information about the functional relations between genes. However, the vast number of observed interactions, along with experimental noise, makes the interpretation of such assays a major challenge. Results: Here, we introduce a computational approach to organize genetic interactions and show that the bulk of observed interactions can be organized in a hierarchy of modules. Revealing this organization enables insights into the function of cellular machineries and highlights global properties of interaction maps. To gain further insight into the nature of these interactions, we integrated data from genetic screens under a wide range of conditions to reveal that more than a third of observed aggravating (i.e. synthetic sick/lethal) interactions are unidirectional, where one gene can buffer the effects of perturbing another gene but not vice versa. Furthermore, most modules of genes that have multiple aggravating interactions were found to be involved in such unidirectional interactions. We demonstrate that the identification of external stimuli that mimic the effect of specific gene knockouts provides insights into the role of individual modules in maintaining cellular integrity. Availability: We designed a freely accessible web tool that includes all our findings, and is specifically intended to allow effective browsing of our results (http://compbio.cs.huji.ac.il/GIAnalysis). Contact: maya.schuldiner@weizmann.ac.il; hanahm@ekmd.huji.ac.il; nir@cs.huji.ac.il Supplementary information: Supplementary data are available at Bioinformatics online.
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spelling pubmed-28813822010-06-08 Modularity and directionality in genetic interaction maps Jaimovich, Ariel Rinott, Ruty Schuldiner, Maya Margalit, Hanah Friedman, Nir Bioinformatics Ismb 2010 Conference Proceedings July 11 to July 13, 2010, Boston, Ma, Usa Motivation: Genetic interactions between genes reflect functional relationships caused by a wide range of molecular mechanisms. Large-scale genetic interaction assays lead to a wealth of information about the functional relations between genes. However, the vast number of observed interactions, along with experimental noise, makes the interpretation of such assays a major challenge. Results: Here, we introduce a computational approach to organize genetic interactions and show that the bulk of observed interactions can be organized in a hierarchy of modules. Revealing this organization enables insights into the function of cellular machineries and highlights global properties of interaction maps. To gain further insight into the nature of these interactions, we integrated data from genetic screens under a wide range of conditions to reveal that more than a third of observed aggravating (i.e. synthetic sick/lethal) interactions are unidirectional, where one gene can buffer the effects of perturbing another gene but not vice versa. Furthermore, most modules of genes that have multiple aggravating interactions were found to be involved in such unidirectional interactions. We demonstrate that the identification of external stimuli that mimic the effect of specific gene knockouts provides insights into the role of individual modules in maintaining cellular integrity. Availability: We designed a freely accessible web tool that includes all our findings, and is specifically intended to allow effective browsing of our results (http://compbio.cs.huji.ac.il/GIAnalysis). Contact: maya.schuldiner@weizmann.ac.il; hanahm@ekmd.huji.ac.il; nir@cs.huji.ac.il Supplementary information: Supplementary data are available at Bioinformatics online. Oxford University Press 2010-06-15 2010-06-01 /pmc/articles/PMC2881382/ /pubmed/20529911 http://dx.doi.org/10.1093/bioinformatics/btq197 Text en © The Author(s) 2010. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/2.0/uk/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Ismb 2010 Conference Proceedings July 11 to July 13, 2010, Boston, Ma, Usa
Jaimovich, Ariel
Rinott, Ruty
Schuldiner, Maya
Margalit, Hanah
Friedman, Nir
Modularity and directionality in genetic interaction maps
title Modularity and directionality in genetic interaction maps
title_full Modularity and directionality in genetic interaction maps
title_fullStr Modularity and directionality in genetic interaction maps
title_full_unstemmed Modularity and directionality in genetic interaction maps
title_short Modularity and directionality in genetic interaction maps
title_sort modularity and directionality in genetic interaction maps
topic Ismb 2010 Conference Proceedings July 11 to July 13, 2010, Boston, Ma, Usa
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2881382/
https://www.ncbi.nlm.nih.gov/pubmed/20529911
http://dx.doi.org/10.1093/bioinformatics/btq197
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