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Active Interaction Mapping Reveals the Hierarchical Organization of Autophagy.

Molecular cell | 2017

We have developed a general progressive procedure, Active Interaction Mapping, to guide assembly of the hierarchy of functions encoding any biological system. Using this process, we assemble an ontology of functions comprising autophagy, a central recycling process implicated in numerous diseases. A first-generation model, built from existing gene networks in Saccharomyces, captures most known autophagy components in broad relation to vesicle transport, cell cycle, and stress response. Systematic analysis identifies synthetic-lethal interactions as most informative for further experiments; consequently, we saturate the model with 156,364 such measurements across autophagy-activating conditions. These targeted interactions provide more information about autophagy than all previous datasets, producing a second-generation ontology of 220 functions. Approximately half are previously unknown; we confirm roles for Gyp1 at the phagophore-assembly site, Atg24 in cargo engulfment, Atg26 in cytoplasm-to-vacuole targeting, and Ssd1, Did4, and others in selective and non-selective autophagy. The procedure and autophagy hierarchy are at http://atgo.ucsd.edu/.

Pubmed ID: 28132844 RIS Download

Associated grants

  • Agency: NHGRI NIH HHS, United States
    Id: U41 HG001315
  • Agency: NHGRI NIH HHS, United States
    Id: F30 HG007618
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM008806
  • Agency: NHGRI NIH HHS, United States
    Id: U41 HG002273
  • Agency: NIGMS NIH HHS, United States
    Id: P41 GM103504
  • Agency: NHGRI NIH HHS, United States
    Id: P41 HG001315
  • Agency: NIEHS NIH HHS, United States
    Id: R01 ES014811
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK041737
  • Agency: NIGMS NIH HHS, United States
    Id: P50 GM085764
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM084279
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM007198

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


Gene Ontology (tool)

RRID:SCR_002811

Computable knowledge regarding functions of genes and gene products. GO resources include biomedical ontologies that cover molecular domains of all life forms as well as extensive compilations of gene product annotations to these ontologies that provide largely species-neutral, comprehensive statements about what gene products do. Used to standardize representation of gene and gene product attributes across species and databases.

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RRID:SCR_008058

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RRID:SCR_008394

Programming language for all operating systems that lets users work more quickly and integrate their systems more effectively. Often compared to Tcl, Perl, Ruby, Scheme or Java. Some of its key distinguishing features include very clear and readable syntax, strong introspection capabilities, intuitive object orientation, natural expression of procedural code, full modularity, exception-based error handling, high level dynamic data types, extensive standard libraries and third party modules for virtually every task, extensions and modules easily written in C, C (or Java for Python, or .NET languages for IronPython), and embeddable within applications as a scripting interface.

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RRID:SCR_003070

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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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