ABSTRACT
Genome-scale screening studies are gradually accumulating a wealth of data on the putative involvement of hundreds of genes in various cellular responses or functions. A fundamental challenge is to chart the molecular pathways that underlie these systems. ANAT is an interactive software tool, implemented as a Cytoscape plug-in, for elucidating functional networks of proteins. It encompasses a number of network inference algorithms and provides access to networks of physical associations in several organisms. In contrast to existing software tools, ANAT can be used to infer subnetworks that connect hundreds of proteins to each other or to a given set of "anchor" proteins, a fundamental step in reconstructing cellular subnetworks. The interactive component of ANAT provides an array of tools for evaluating and exploring the resulting subnetwork models and for iteratively refining them. We demonstrate the utility of ANAT by studying the crosstalk between the autophagic and apoptotic cell death modules in humans, using a network of physical interactions. Relative to published software tools, ANAT is more accurate and provides more features for comprehensive network analysis. The latest version of the software is available at http://www.cs.tau.ac.il/~bnet/ANAT_SI.
Subject(s)
Algorithms , Protein Interaction Mapping/methods , Proteins/metabolism , Signal Transduction/physiology , Software , Animals , Apoptosis/genetics , Apoptosis/physiology , Arabidopsis/genetics , Arabidopsis/metabolism , Autophagy/genetics , Autophagy/physiology , Caenorhabditis elegans/genetics , Caenorhabditis elegans/metabolism , Drosophila melanogaster/genetics , Drosophila melanogaster/metabolism , Escherichia coli/genetics , Escherichia coli/metabolism , Genome/genetics , Helicobacter pylori/genetics , Helicobacter pylori/metabolism , Humans , Internet , Mice , Models, Biological , Plasmodium falciparum/genetics , Plasmodium falciparum/metabolism , Proteins/genetics , Rats , Reproducibility of Results , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Signal Transduction/geneticsABSTRACT
SUMMARY: PRINCIPLE is a Java application implemented as a Cytoscape plug-in, based on a previously published algorithm, PRINCE. Given a query disease, it prioritizes disease-related genes based on their closeness in a protein-protein interaction network to genes causing phenotypically similar disorders to the query disease. AVAILABILITY: Implemented in Java, PRINCIPLE runs over Cytoscape 2.7 or newer versions. Binaries, default input files and documentation are freely available at http://www.cs.tau.ac.il/~bnet/software/PrincePlugin/. CONTACT: roded@tau.ac.il; assafgot@tau.ac.il.
