Probabilistic prediction and ranking of human protein-protein interactions.
BACKGROUND
Although the prediction of protein-protein interactions has been extensively investigated for yeast, few such datasets exist for the far larger proteome in human. Furthermore, it has recently been estimated that the overall average false positive rate of available computational and high-throughput experimental interaction datasets is as high as 90%.


RESULTS
The prediction of human protein-protein interactions was investigated by combining orthogonal protein features within a probabilistic framework. The features include co-expression, orthology to known interacting proteins and the full-Bayesian combination of subcellular localization, co-occurrence of domains and post-translational modifications. A novel scoring function for local network topology was also investigated. This topology feature greatly enhanced the predictions and together with the full-Bayes combined features, made the largest contribution to the predictions. Using a conservative threshold, our most accurate predictor identifies 37606 human interactions, 32892 (80%) of which are not present in other publicly available large human interaction datasets, thus substantially increasing the coverage of the human interaction map. A subset of the 32892 novel predicted interactions have been independently validated. Comparison of the prediction dataset to other available human interaction datasets estimates the false positive rate of the new method to be below 80% which is competitive with other methods. Since the new method scores and ranks all human protein pairs, smaller subsets of higher quality can be generated thus leading to even lower false positive prediction rates.


CONCLUSIONS
The set of interactions predicted in this work increases the coverage of the human interaction map and will help determine the highest confidence human interactions.
Scott
Michelle S
MS
School of Life Sciences Research, College of Life Sciences, University of Dundee, Scotland, UK. michelle@compbio.dundee.ac.uk <michelle@compbio.dundee.ac.uk>
Barton
Geoffrey J
GJ
D001499:Bayes Theorem; D001665:Binding Sites; D016009:Chi-Square Distribution; D019295:Computational Biology / Q000379:methods*; D030562:Databases, Protein; D005189:False Positive Reactions; D005544:Forecasting; D006801:Humans; D016013:Likelihood Functions; D016017:Odds Ratio; D011336:Probability; D011485:Protein Binding; D025941:Protein Interaction Mapping / Q000379:methods* / Q000706:statistics & numerical data; D017434:Protein Structure, Tertiary; D020543:Proteome; D012372:ROC Curve; D015203:Reproducibility of Results
D020543:Proteome