Predicting protein-protein interactions using high-quality non-interacting pairs

Abstract

BackgroundIdentifying protein-protein interactions (PPIs) is of paramount importance for understanding cellular processes. Machine learning-based approaches have been developed to predict PPIs, but the effectiveness of these approaches is unsatisfactory. One major reason is that they randomly choose non-interacting protein pairs (negative samples) or heuristically select non-interacting pairs with low quality.ResultsTo boost the effectiveness of predicting PPIs, we propose two novel approaches (NIP-SS and NIP-RW) to generate high quality non-interacting pairs based on sequence similarity and random walk, respectively. Specifically, the known PPIs collected from public databases are used to generate the positive samples. NIP-SS then selects the top-m dissimilar protein pairs as negative examples and controls the degree distribution of selected proteins to construct the negative dataset. NIP-RW performs random walk on the PPI network to update the adjacency matrix of the network, and then selects protein pairs not connected in the updated network as negative samples. Next, we use auto covariance (AC) descriptor to encode the feature information of amino acid sequences. After that, we employ deep neural networks (DNNs) to predict PPIs based on extracted features, positive and negative examples. Extensive experiments show that NIP-SS and NIP-RW can generate negative samples with higher quality than existing strategies and thus enable more accurate prediction.ConclusionsThe experimental results prove that negative datasets constructed by NIP-SS and NIP-RW can reduce the bias and have good generalization ability. NIP-SS and NIP-RW can be used as a plugin to boost the effectiveness of PPIs prediction. Codes and datasets are available at http://mlda.swu.edu.cn/codes.php?name=NIP.