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A computational interactome and functional annotation for the human proteome.

eLife | 2016

We present a database, PrePPI (Predicting Protein-Protein Interactions), of more than 1.35 million predicted protein-protein interactions (PPIs). Of these at least 127,000 are expected to constitute direct physical interactions although the actual number may be much larger (~500,000). The current PrePPI, which contains predicted interactions for about 85% of the human proteome, is related to an earlier version but is based on additional sources of interaction evidence and is far larger in scope. The use of structural relationships allows PrePPI to infer numerous previously unreported interactions. PrePPI has been subjected to a series of validation tests including reproducing known interactions, recapitulating multi-protein complexes, analysis of disease associated SNPs, and identifying functional relationships between interacting proteins. We show, using Gene Set Enrichment Analysis (GSEA), that predicted interaction partners can be used to annotate a protein's function. We provide annotations for most human proteins, including many annotated as having unknown function.

Pubmed ID: 27770567 RIS Download

Research resources used in this publication

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Antibodies used in this publication

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Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM030518
  • Agency: NIH HHS, United States
    Id: S10 OD012351
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM109018
  • Agency: NIGMS NIH HHS, United States
    Id: R37 GM030518
  • Agency: NIH HHS, United States
    Id: S10 OD021764

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


IntAct (tool)

RRID:SCR_006944

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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PIPs- Human Protein-protein Interaction Prediction (tool)

RRID:SCR_007857

A database of predicted human protein-protein interactions. The predictions have been made using a naïve Bayesian classifier to calculate a Score of interaction. There are 37606 interactions with a Score ≥1 indicating that the interaction is more likely to occur than not to occur.

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InParanoid: Eukaryotic Ortholog Groups (tool)

RRID:SCR_006801

Collection of pairwise comparisons between 100 whole genomes generated by a fully automatic method for finding orthologs and in-paralogs between TWO species. Ortholog clusters in the InParanoid are seeded with a two-way best pairwise match, after which an algorithm for adding in-paralogs is applied. The method bypasses multiple alignments and phylogenetic trees, which can be slow and error-prone steps in classical ortholog detection. Still, it robustly detects complex orthologous relationships and assigns confidence values for in-paralogs. The original data sets can be downloaded.

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STRING (tool)

RRID:SCR_005223

Database of known and predicted protein interactions. The interactions include direct (physical) and indirect (functional) associations and are derived from four sources: Genomic Context, High-throughput experiments, (Conserved) Coexpression, and previous knowledge. STRING quantitatively integrates interaction data from these sources for a large number of organisms, and transfers information between these organisms where applicable. The database currently covers 5''214''234 proteins from 1133 organisms. (2013)

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HumanNet (tool)

RRID:SCR_016146

Database of human protein-encoding genes that is constructed by a modified Bayesian integration of 'omics' data from multiple organisms. Each data type is weighted according to how well it links genes that are known to function together in humans, and each interaction has an associated log-likelihood score (LLS) that measures the probability of an interaction representing a true functional linkage between two genes.

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