Abstract

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.

Data availability

The following previously published data sets were used

Article and author information

Author details

  1. José Ignacio Garzón

    Center for Computational Biology and Bioinformatics, Department of Systems Biology, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Lei Deng

    Center for Computational Biology and Bioinformatics, Department of Systems Biology, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Diana Murray

    Center for Computational Biology and Bioinformatics, Department of Systems Biology, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Sagi Shapira

    Center for Computational Biology and Bioinformatics, Department of Systems Biology, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Donald Petrey

    Center for Computational Biology and Bioinformatics, Department of Systems Biology, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Barry Honig

    Center for Computational Biology and Bioinformatics, Department of Systems Biology, Columbia University, New York, United States
    For correspondence
    bh6@cumc.columbia.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2480-6696

Funding

National Institutes of Health (GM030518)

  • Barry Honig

National Institutes of Health (S10OD012351)

  • José Ignacio Garzón
  • Lei Deng
  • Diana Murray
  • Sagi Shapira
  • Donald Petrey
  • Barry Honig

National Institutes of Health (S10OD021764)

  • José Ignacio Garzón
  • Lei Deng
  • Diana Murray
  • Sagi Shapira
  • Donald Petrey
  • Barry Honig

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Nir Ben-Tal, Tel Aviv University, Israel

Version history

  1. Received: June 11, 2016
  2. Accepted: October 19, 2016
  3. Accepted Manuscript published: October 22, 2016 (version 1)
  4. Version of Record published: November 18, 2016 (version 2)

Copyright

© 2016, Garzón et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 3,615
    views
  • 781
    downloads
  • 49
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. José Ignacio Garzón
  2. Lei Deng
  3. Diana Murray
  4. Sagi Shapira
  5. Donald Petrey
  6. Barry Honig
(2016)
A computational interactome and functional annotation for the human proteome
eLife 5:e18715.
https://doi.org/10.7554/eLife.18715

Share this article

https://doi.org/10.7554/eLife.18715

Further reading

    1. Computational and Systems Biology
    2. Genetics and Genomics
    Weichen Song, Yongyong Shi, Guan Ning Lin
    Tools and Resources

    We propose a new framework for human genetic association studies: at each locus, a deep learning model (in this study, Sei) is used to calculate the functional genomic activity score for two haplotypes per individual. This score, defined as the Haplotype Function Score (HFS), replaces the original genotype in association studies. Applying the HFS framework to 14 complex traits in the UK Biobank, we identified 3619 independent HFS–trait associations with a significance of p < 5 × 10−8. Fine-mapping revealed 2699 causal associations, corresponding to a median increase of 63 causal findings per trait compared with single-nucleotide polymorphism (SNP)-based analysis. HFS-based enrichment analysis uncovered 727 pathway–trait associations and 153 tissue–trait associations with strong biological interpretability, including ‘circadian pathway-chronotype’ and ‘arachidonic acid-intelligence’. Lastly, we applied least absolute shrinkage and selection operator (LASSO) regression to integrate HFS prediction score with SNP-based polygenic risk scores, which showed an improvement of 16.1–39.8% in cross-ancestry polygenic prediction. We concluded that HFS is a promising strategy for understanding the genetic basis of human complex traits.

    1. Computational and Systems Biology
    Qianmu Yuan, Chong Tian, Yuedong Yang
    Tools and Resources

    Revealing protein binding sites with other molecules, such as nucleic acids, peptides, or small ligands, sheds light on disease mechanism elucidation and novel drug design. With the explosive growth of proteins in sequence databases, how to accurately and efficiently identify these binding sites from sequences becomes essential. However, current methods mostly rely on expensive multiple sequence alignments or experimental protein structures, limiting their genome-scale applications. Besides, these methods haven’t fully explored the geometry of the protein structures. Here, we propose GPSite, a multi-task network for simultaneously predicting binding residues of DNA, RNA, peptide, protein, ATP, HEM, and metal ions on proteins. GPSite was trained on informative sequence embeddings and predicted structures from protein language models, while comprehensively extracting residual and relational geometric contexts in an end-to-end manner. Experiments demonstrate that GPSite substantially surpasses state-of-the-art sequence-based and structure-based approaches on various benchmark datasets, even when the structures are not well-predicted. The low computational cost of GPSite enables rapid genome-scale binding residue annotations for over 568,000 sequences, providing opportunities to unveil unexplored associations of binding sites with molecular functions, biological processes, and genetic variants. The GPSite webserver and annotation database can be freely accessed at https://bio-web1.nscc-gz.cn/app/GPSite.