scholarly journals A multitask transfer learning framework for the prediction of virus-human protein–protein interactions

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Thi Ngan Dong ◽  
Graham Brogden ◽  
Gisa Gerold ◽  
Megha Khosla

Abstract Background Viral infections are causing significant morbidity and mortality worldwide. Understanding the interaction patterns between a particular virus and human proteins plays a crucial role in unveiling the underlying mechanism of viral infection and pathogenesis. This could further help in prevention and treatment of virus-related diseases. However, the task of predicting protein–protein interactions between a new virus and human cells is extremely challenging due to scarce data on virus-human interactions and fast mutation rates of most viruses. Results We developed a multitask transfer learning approach that exploits the information of around 24 million protein sequences and the interaction patterns from the human interactome to counter the problem of small training datasets. Instead of using hand-crafted protein features, we utilize statistically rich protein representations learned by a deep language modeling approach from a massive source of protein sequences. Additionally, we employ an additional objective which aims to maximize the probability of observing human protein–protein interactions. This additional task objective acts as a regularizer and also allows to incorporate domain knowledge to inform the virus-human protein–protein interaction prediction model. Conclusions Our approach achieved competitive results on 13 benchmark datasets and the case study for the SARS-CoV-2 virus receptor. Experimental results show that our proposed model works effectively for both virus-human and bacteria-human protein–protein interaction prediction tasks. We share our code for reproducibility and future research at https://git.l3s.uni-hannover.de/dong/multitask-transfer.

2021 ◽  
Author(s):  
Joseph Szymborski ◽  
Amin Emad

Motivation: Computational methods for the prediction of protein-protein interactions, while important tools for researchers, are plagued by challenges in generalising to unseen proteins. Datasets used for modelling protein-protein predictions are particularly predisposed to information leakage and sampling biases. Results: In this study, we introduce RAPPPID, a method for the Regularised Automatic Prediction of Protein-Protein Interactions using Deep Learning. RAPPPID is a twin AWD-LSTM network which employs multiple regularisation methods during training time to learn generalised weights. Testing on stringent interaction datasets composed of proteins not seen during training, RAPPPID outperforms state-of-the-art methods. Further experiments show that RAPPPID's performance holds regardless of the particular proteins in the testing set and its performance is higher for biologically supported edges. This study serves to demonstrate that appropriate regularisation is an important component of overcoming the challenges of creating models for protein-protein interaction prediction that generalise to unseen proteins. Availability and Implementation: Code and datasets are freely available at https://github.com/jszym/rapppid. Contact: [email protected] Supplementary Information: Online-only supplementary data is available at the journal's website.


Author(s):  
Guofeng Lv ◽  
Zhiqiang Hu ◽  
Yanguang Bi ◽  
Shaoting Zhang

The study of multi-type Protein-Protein Interaction (PPI) is fundamental for understanding biological processes from a systematic perspective and revealing disease mechanisms. Existing methods suffer from significant performance degradation when tested in unseen dataset. In this paper, we investigate the problem and find that it is mainly attributed to the poor performance for inter-novel-protein interaction prediction. However, current evaluations overlook the inter-novel-protein interactions, and thus fail to give an instructive assessment. As a result, we propose to address the problem from both the evaluation and the methodology. Firstly, we design a new evaluation framework that fully respects the inter-novel-protein interactions and gives consistent assessment across datasets. Secondly, we argue that correlations between proteins must provide useful information for analysis of novel proteins, and based on this, we propose a graph neural network based method (GNN-PPI) for better inter-novel-protein interaction prediction. Experimental results on real-world datasets of different scales demonstrate that GNN-PPI significantly outperforms state-of-the-art PPI prediction methods, especially for the inter-novel-protein interaction prediction.


Genomics ◽  
2014 ◽  
Vol 104 (6) ◽  
pp. 496-503 ◽  
Author(s):  
Javad Zahiri ◽  
Morteza Mohammad-Noori ◽  
Reza Ebrahimpour ◽  
Samaneh Saadat ◽  
Joseph H. Bozorgmehr ◽  
...  

PLoS Genetics ◽  
2021 ◽  
Vol 17 (11) ◽  
pp. e1009869
Author(s):  
Jiajun Qiu ◽  
Kui Chen ◽  
Chunlong Zhong ◽  
Sihao Zhu ◽  
Xiao Ma

The perturbations of protein-protein interactions (PPIs) were found to be the main cause of cancer. Previous PPI prediction methods which were trained with non-disease general PPI data were not compatible to map the PPI network in cancer. Therefore, we established a novel cancer specific PPI prediction method dubbed NECARE, which was based on relational graph convolutional network (R-GCN) with knowledge-based features. It achieved the best performance with a Matthews correlation coefficient (MCC) = 0.84±0.03 and an F1 = 91±2% compared with other methods. With NECARE, we mapped the cancer interactome atlas and revealed that the perturbations of PPIs were enriched on 1362 genes, which were named cancer hub genes. Those genes were found to over-represent with mutations occurring at protein-macromolecules binding interfaces. Furthermore, over 56% of cancer treatment-related genes belonged to hub genes and they were significantly related to the prognosis of 32 types of cancers. Finally, by coimmunoprecipitation, we confirmed that the NECARE prediction method was highly reliable with a 90% accuracy. Overall, we provided the novel network-based cancer protein-protein interaction prediction method and mapped the perturbation of cancer interactome. NECARE is available at: https://github.com/JiajunQiu/NECARE.


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