Abstract

BackgroundBiological processes in cells are carried out by means of protein-protein interactions. Determining whether a pair of proteins interacts by wet-lab experiments is resource-intensive; only about 38,000 interactions, out of a few hundred thousand expected interactions, are known today. Active machine learning can guide the selection of pairs of proteins for future experimental characterization in order to accelerate accurate prediction of the human protein interactome.ResultsRandom forest (RF) has previously been shown to be effective for predicting protein-protein interactions. Here, four different active learning algorithms have been devised for selection of protein pairs to be used to train the RF. With labels of as few as 500 protein-pairs selected using any of the four active learning methods described here, the classifier achieved a higher F-score (harmonic mean of Precision and Recall) than with 3000 randomly chosen protein-pairs. F-score of predicted interactions is shown to increase by about 15% with active learning in comparison to that with random selection of data.ConclusionActive learning algorithms enable learning more accurate classifiers with much lesser labelled data and prove to be useful in applications where manual annotation of data is formidable. Active learning techniques demonstrated here can also be applied to other proteomics applications such as protein structure prediction and classification.

Highlights

  • Biological processes in cells are carried out by means of protein-protein interactions

  • The vectors have 27 dimensions and contain features corresponding to Gene Ontology (GO) cell component (1), GO molecular function (1), GO biological process (1), co-occurrence in tissue (1), gene expression (16), sequence similarity (1), homology based (5) and domain interaction (1), where the numbers in brackets correspond to the number of elements contributed by the feature type to the feature vector

  • The GO features measure similarity of two genes based on the similarity between the terms they share in the Gene Ontology database

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Summary

Introduction

Biological processes in cells are carried out by means of protein-protein interactions. Several high throughput methods such as Yeast 2-Hybrid (Y2H) and mass spectrometry methods help determine protein interactions. These methods suffer from high false positive rates, and many protein interaction predictions supported by one method are not supported by another. In complex organisms like human, applying high throughput methods to test every possible protein pair (which is in the order of 108) would be very expensive in terms of cost and effort. Computational methods are necessary to complete the interactome expeditiously

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