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Large-scale mapping of human protein-protein interactions by mass spectrometry.

Molecular systems biology | Mar 13, 2007

Mapping protein-protein interactions is an invaluable tool for understanding protein function. Here, we report the first large-scale study of protein-protein interactions in human cells using a mass spectrometry-based approach. The study maps protein interactions for 338 bait proteins that were selected based on known or suspected disease and functional associations. Large-scale immunoprecipitation of Flag-tagged versions of these proteins followed by LC-ESI-MS/MS analysis resulted in the identification of 24,540 potential protein interactions. False positives and redundant hits were filtered out using empirical criteria and a calculated interaction confidence score, producing a data set of 6463 interactions between 2235 distinct proteins. This data set was further cross-validated using previously published and predicted human protein interactions. In-depth mining of the data set shows that it represents a valuable source of novel protein-protein interactions with relevance to human diseases. In addition, via our preliminary analysis, we report many novel protein interactions and pathway associations.

Pubmed ID: 17353931 RIS Download

Mesh terms: Humans | Immunoprecipitation | Protein Binding | Proteins | Spectrometry, Mass, Electrospray Ionization

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MatrixScience

A collection of both commercial and noncommercial software products which includes: Mascot Distiller, Mascot Parser, and Mascot Server. Mascot Distiller is commercial and provides a single interface to process raw data into de-isotoped peak lists. This tool can also be used for the easy distribution of search and quantitative results to colleagues. The non-commercial Mascot Parser software provides an API (Application Programmer Interface) that makes it easier to access search results written in C++, Java, Python and Perl. Mascot Server is non-commercial, and is a collection of peptide mass fingerprints as well as a MS/MS database. A selection of popular sequence databases are available online and include SwissProt, NCBInr, and the EST divisions of EMBL. This server is best used for evaluating and searching for smaller data sets.

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GO

A community-based bioinformatics resource consisting of three structured controlled vocabularies (ontologies) for the annotation of gene products with respect to their molecular function, cellular component, and biological role in a species-independent manner. This initiative to standardize the representation of gene and gene product attributes across species and databases is an effort to address the need for consistent descriptions of gene products in different databases. The Gene Ontology project encourages input from the community into both the content of the GO and annotation using GO. There are three separate aspects to this effort: first, they write and maintain the ontologies themselves; second, they make cross-links between the ontologies and the genes and gene products in the collaborating databases; and third, they develop tools that facilitate the creation, maintenance and use of ontologies. The controlled vocabularies are structured so that users can query them at different levels: for example, uers can use GO to find all the gene products in the mouse genome that are involved in signal transduction, or users can zoom in on all the receptor tyrosine kinases. This structure also allows annotators to assign properties to gene products at different levels, depending on how much is known about a gene product.

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Cytoscape

An open source bioinformatics software platform for visualizing molecular interaction networks and biological pathways and integrating these networks with annotations, gene expression profiles and other state data. Although Cytoscape was originally designed for biological research, now it is a general platform for complex network analysis and visualization. Additional features are available as plugins. Plugins are available for network and molecular profiling analyses, new layouts, additional file format support, scripting, and connection with databases. Plugins may be developed by anyone using the Cytoscape open API based on Java technology and plugin community development is encouraged. Most of the plugins are freely available. Cytoscape works as a web service client. This means Cytoscape can directly connect to the external public databases and imports network and annotation data. Currently, Pathway Commons, IntAct, BioMart, NCBI Entrez Gene, and PICR are supported. And they continue to develop new service clients for popular databases.

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IntAct

Open source database system and analysis tools for molecular interaction data. All interactions are derived from literature curation or direct user submissions. Direct user submissions of molecular interaction data are encouraged, which may be deposited prior to publication in a peer-reviewed journal. The IntAct Database contains (Jun. 2014): * 447368 Interactions * 33021 experiments * 12698 publications * 82745 Interactors IntAct provides a two-tiered view of the interaction data. The search interface allows the user to iteratively develop complex queries, exploiting the detailed annotation with hierarchical controlled vocabularies. Results are provided at any stage in a simplified, tabular view. Specialized views then allows "zooming in" on the full annotation of interactions, interactors and their properties. IntAct source code and data are freely available.

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Molecular Probes

An Antibody supplier and subset of ThermoFisher Scientific which provides fluorescence reagents for various experiments and methods.

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