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Time-resolved mapping of genetic interactions to model rewiring of signaling pathways.

eLife | 2018

Context-dependent changes in genetic interactions are an important feature of cellular pathways and their varying responses under different environmental conditions. However, methodological frameworks to investigate the plasticity of genetic interaction networks over time or in response to external stresses are largely lacking. To analyze the plasticity of genetic interactions, we performed a combinatorial RNAi screen in Drosophila cells at multiple time points and after pharmacological inhibition of Ras signaling activity. Using an image-based morphology assay to capture a broad range of phenotypes, we assessed the effect of 12768 pairwise RNAi perturbations in six different conditions. We found that genetic interactions form in different trajectories and developed an algorithm, termed MODIFI, to analyze how genetic interactions rewire over time. Using this framework, we identified more statistically significant interactions compared to end-point assays and further observed several examples of context-dependent crosstalk between signaling pathways such as an interaction between Ras and Rel which is dependent on MEK activity.

Pubmed ID: 30592458 RIS Download

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This is a list of tools and resources that we have found mentioned in this publication.


ATCC (tool)

RRID:SCR_001672

Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.

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LIMMA (tool)

RRID:SCR_010943

Software package for the analysis of gene expression microarray data, especially the use of linear models for analyzing designed experiments and the assessment of differential expression.

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BIOMOL (tool)

RRID:SCR_013545

An Antibody supplier

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CRAN (tool)

RRID:SCR_003005

Network of ftp and web servers around world that store identical, up to date, versions of code and documentation for R. Package archive network for R programming language.

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Phalloidin-TRITC (antibody)

RRID:AB_2315148

This unknown targets

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Monoclonal Anti-alpha-Tubulin-FITC antibody produced in mouse (antibody)

RRID:AB_476967

This monoclonal targets alpha-Tubulin-FITC antibody produced in mouse

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Comprehensive Perl Archive Network (data or information resource)

RRID:SCR_007253

Welcome to CPAN, where you you will find All Things Perl. CPAN is the Comprehensive Perl Archive Network, a large collection of Perl software and documentation. You can begin exploring from either http://www.cpan.org/, http://www.perl.com/CPAN/ or any of the mirrors listed at http://www.cpan.org/SITES.html. Note that CPAN is also the name of a Perl module, CPAN.pm, which is used to download and install Perl software from the CPAN archive. This FAQ covers only a little about the CPAN module and you may find the documentation for it by using perldoc CPAN via the command line or on the web at http://search.cpan.org/dist/CPAN/lib/CPAN.pm. Sponsors: CPAN works with the generosity and cooperation of hundreds of developers, over 100 participating mirrors, funet.fi donating the network bandwidth, storage space and computing power, volunteers who help keep everything together and users whose interest in Perl keep the archive alive and growing. Keywords: Comprehension, Perl, Archive, Software, Documentation,

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R Project for Statistical Computing (software resource)

RRID:SCR_001905

Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.

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FlyBase (data repository)

RRID:SCR_006549

Database of Drosophila genetic and genomic information with information about stock collections and fly genetic tools. Gene Ontology (GO) terms are used to describe three attributes of wild-type gene products: their molecular function, the biological processes in which they play a role, and their subcellular location. Additionally, FlyBase accepts data submissions. FlyBase can be searched for genes, alleles, aberrations and other genetic objects, phenotypes, sequences, stocks, images and movies, controlled terms, and Drosophila researchers using the tools available from the "Tools" drop-down menu in the Navigation bar.

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Schneider 2 (cell line)

RRID:CVCL_Z232

Cell line Schneider 2 is a Spontaneously immortalized cell line with a species of origin Drosophila melanogaster

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