Accurate in-silico identification of protein-protein interactions (PPIs) is a long-standing problem in biology, with important implications in protein function prediction and drug design. Current computational approaches predominantly use a single data modality for describing protein pairs, which may not fully capture the characteristics relevant for identifying PPIs. Another limitation of existing methods is their poor generalization to proteins outside the training graph. In this paper, we aim to address these shortcomings by proposing a new ensemble approach for PPI prediction, which learns information from two modalities, corresponding to pairs of sequences and to the graph formed by the training proteins and their interactions. Our approach uses a siamese neural network to process sequence information, while graph attention networks are employed for the network view. For capturing the relationships between the proteins in a pair, we design a new feature fusion module, based on computing the distance between the distributions corresponding to the two proteins. The prediction is made using a stacked generalization procedure, in which the final classifier is represented by a Logistic Regression model trained on the scores predicted by the sequence and graph models. Additionally, we show that protein sequence embeddings obtained using pretrained language models can significantly improve the generalization of PPI methods. The experimental results demonstrate the good performance of our approach, which surpasses all the related work on two Yeast data sets, while outperforming the majority of literature approaches on two Human data sets and on independent multi-species data sets.

• PMID: 36623437
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Journal Article | Research Support, Non-U.S. Gov't

Authors

Albu AI, Bocicor MI, Czibula G

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