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Mapping Dysfunctional Protein-Protein Interactions in Disease
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Context-specific interactions in literature-curated protein interaction databases.

R Greg Stacey1, Michael A Skinnider2, Jenny H L Chik3

  • 1Michael Smith Laboratories, University of British Columbia, Vancouver, V6T 1Z4, Canada. richard.greg.stacey@msl.ubc.ca.

BMC Genomics
|October 21, 2018
PubMed
Summary
This summary is machine-generated.

Literature-curated protein-protein interaction (PPI) databases often fail as gold standards in interactome mapping. A specific subset of CORUM database complexes consistently shows interaction evidence, improving interactome mapping accuracy.

Keywords:
InteractomeLiterature curated databaseProtein-protein interactionProteomics

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Area of Science:

  • Proteomics
  • Systems Biology
  • Bioinformatics

Background:

  • Literature-curated protein-protein interaction (PPI) databases are crucial for interpreting high-throughput interactome mapping studies.
  • These databases aggregate interactions from numerous studies and experimental techniques, leading to condition-specific heterogeneity.
  • A common assumption is that all PPIs in gold standard databases interact under the experimental conditions of a given study.

Purpose of the Study:

  • To evaluate the validity of using comprehensive PPI databases as gold standards in interactome mapping.
  • To identify a reliable subset of PPIs that consistently interact under specific experimental conditions.
  • To improve the accuracy of interactome mapping by utilizing context-specific gold standards.

Main Methods:

  • Analysis of raw data from 20 co-fractionation experiments.
  • Comparison with six published interactomes.
  • Identification and validation of a subset of CORUM database complexes exhibiting consistent co-fractionation profiles.

Main Results:

  • Up to 55% of purported gold standard interactions lacked evidence of interaction in co-fractionation experiments.
  • A specific subset of CORUM database complexes demonstrated consistent interaction evidence.
  • Utilizing this CORUM subset as gold standards significantly enhanced interactome mapping, increasing predicted interactions at a given error rate.

Conclusions:

  • A subset of CORUM database complexes serves as a reliable gold standard for co-fractionation studies.
  • Using context-specific PPI subsets improves the interpretation of interactome mapping data.
  • Future interactome mapping studies should prioritize context-specific gold standard sets for greater accuracy.