HINT: High-quality protein interactomes and their applications in understanding human disease

BMC Syst Biol. 2012 Jul 30;6:92. doi: 10.1186/1752-0509-6-92.


Background: A global map of protein-protein interactions in cellular systems provides key insights into the workings of an organism. A repository of well-validated high-quality protein-protein interactions can be used in both large- and small-scale studies to generate and validate a wide range of functional hypotheses.

Results: We develop HINT (http://hint.yulab.org) - a database of high-quality protein-protein interactomes for human, Saccharomyces cerevisiae, Schizosaccharomyces pombe, and Oryza sativa. These were collected from several databases and filtered both systematically and manually to remove low-quality/erroneous interactions. The resulting datasets are classified by type (binary physical interactions vs. co-complex associations) and data source (high-throughput systematic setups vs. literature-curated small-scale experiments). We find strong sociological sampling biases in literature-curated datasets of small-scale interactions. An interactome without such sampling biases was used to understand network properties of human disease-genes - hubs are unlikely to cause disease, but if they do, they usually cause multiple disorders.

Conclusions: HINT is of significant interest to researchers in all fields of biology as it addresses the ubiquitous need of having a repository of high-quality protein-protein interactions. These datasets can be utilized to generate specific hypotheses about specific proteins and/or pathways, as well as analyzing global properties of cellular networks. HINT will be regularly updated and all versions will be tracked.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Databases, Protein*
  • Disease* / genetics
  • Humans
  • Oryza / genetics
  • Oryza / metabolism
  • Plant Proteins / genetics
  • Plant Proteins / metabolism
  • Protein Interaction Maps*
  • Quality Control
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces / metabolism
  • Schizosaccharomyces pombe Proteins / genetics
  • Schizosaccharomyces pombe Proteins / metabolism


  • Plant Proteins
  • Saccharomyces cerevisiae Proteins
  • Schizosaccharomyces pombe Proteins