CSGNN: Contrastive Self-Supervised Graph Neural Network for Molecular Interaction Prediction

Molecular interactions are significant resources for analyzing sophisticated biological systems. Identification of multifarious molecular interactions attracts increasing attention in biomedicine, bioinformatics, and human healthcare communities. Recently, a plethora of methods have been proposed to reveal molecular interactions in one specific domain. However, existing methods heavily rely on features or structures involving molecules, which limits the capacity of transferring the models to other tasks. Therefore, generalized models for the multifarious molecular interaction prediction (MIP) are in demand. In this paper, we propose a contrastive self-supervised graph neural network (CSGNN) to predict molecular interactions. CSGNN injects a mix-hop neighborhood aggregator into a graph neural network (GNN) to capture high-order dependency in the molecular interaction networks and leverages a contrastive self-supervised learning task as a regularizer within a multi-task learning paradigm to enhance the generalization ability. Experiments on seven molecular interaction networks show that CSGNN outperforms classic and state-of-the-art models. Comprehensive experiments indicate that the mix-hop aggregator and the self-supervised regularizer can effectively facilitate the link inference in multifarious molecular networks.

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SkipGNN: predicting molecular interactions with skip-graph networks

Scientific Reports ◽

10.1038/s41598-020-77766-9 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Kexin Huang ◽

Cao Xiao ◽

Lucas M. Glass ◽

Marinka Zitnik ◽

Jimeng Sun

Keyword(s):

Neural Network ◽

Molecular Interactions ◽

Biological Networks ◽

Interaction Network ◽

Interaction Networks ◽

Original Graph ◽

Neural Network Approach ◽

Molecular Interaction Networks ◽

Current Graph ◽

Fusion Scheme

AbstractMolecular interaction networks are powerful resources for molecular discovery. They are increasingly used with machine learning methods to predict biologically meaningful interactions. While deep learning on graphs has dramatically advanced the prediction prowess, current graph neural network (GNN) methods are mainly optimized for prediction on the basis of direct similarity between interacting nodes. In biological networks, however, similarity between nodes that do not directly interact has proved incredibly useful in the last decade across a variety of interaction networks. Here, we present SkipGNN, a graph neural network approach for the prediction of molecular interactions. SkipGNN predicts molecular interactions by not only aggregating information from direct interactions but also from second-order interactions, which we call skip similarity. In contrast to existing GNNs, SkipGNN receives neural messages from two-hop neighbors as well as immediate neighbors in the interaction network and non-linearly transforms the messages to obtain useful information for prediction. To inject skip similarity into a GNN, we construct a modified version of the original network, called the skip graph. We then develop an iterative fusion scheme that optimizes a GNN using both the skip graph and the original graph. Experiments on four interaction networks, including drug–drug, drug–target, protein–protein, and gene–disease interactions, show that SkipGNN achieves superior and robust performance. Furthermore, we show that unlike popular GNNs, SkipGNN learns biologically meaningful embeddings and performs especially well on noisy, incomplete interaction networks.

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Computational Analysis of Molecular Interaction Networks Underlying Change of HIV-1 Resistance to Selected Reverse Transcriptase Inhibitors

Bioinformatics and Biology Insights ◽

10.4137/bbi.s6247 ◽

2010 ◽

Vol 4 ◽

pp. BBI.S6247 ◽

Cited By ~ 3

Author(s):

Marcin Kierczak ◽

Michał Dramiński ◽

Jacek Koronacki ◽

Jan Komorowski

Keyword(s):

Drug Resistance ◽

Reverse Transcriptase ◽

Molecular Interaction ◽

3D Structure ◽

Resistance Mechanisms ◽

Interaction Networks ◽

Resistance Level ◽

Molecular Interaction Networks ◽

Monte Carlo Feature Selection ◽

Hiv 1

Motivation Despite more than two decades of research, HIV resistance to drugs remains a serious obstacle in developing efficient AIDS treatments. Several computational methods have been developed to predict resistance level from the sequence of viral proteins such as reverse transcriptase (RT) or protease. These methods, while powerful and accurate, give very little insight into the molecular interactions that underly acquisition of drug resistance/hypersusceptibility. Here, we attempt at filling this gap by using our Monte Carlo feature selection and interdependency discovery method (MCFS-ID) to elucidate molecular interaction networks that characterize viral strains with altered drug resistance levels. Results We analyzed a number of HIV-1 RT sequences annotated with drug resistance level using the MCFS-ID method. This let us expound interdependency networks that characterize change of drug resistance to six selected RT inhibitors: Abacavir, Lamivudine, Stavudine, Zidovudine, Tenofovir and Nevirapine. The networks consider interdependencies at the level of physicochemical properties of mutating amino acids, eg,: polarity. We mapped each network on the 3D structure of RT in attempt to understand the molecular meaning of interacting pairs. The discovered interactions describe several known drug resistance mechanisms and, importantly, some previously unidentified ones. Our approach can be easily applied to a whole range of problems from the domain of protein engineering. Availability A portable Java implementation of our MCFS-ID method is freely available for academic users and can be obtained at: http://www.ipipan.eu/staff/m.draminski/software.htm .

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A Graph Feature Auto-Encoder for the prediction of unobserved node features on biological networks

BMC Bioinformatics ◽

10.1186/s12859-021-04447-3 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Ramin Hasibi ◽

Tom Michoel

Keyword(s):

Gene Expression ◽

Neural Networks ◽

Gene Expression Data ◽

Biological Networks ◽

Molecular Interaction ◽

Interaction Networks ◽

Omics Data ◽

Expression Data ◽

Molecular Interaction Networks ◽

Graph Neural Networks

Abstract Background Molecular interaction networks summarize complex biological processes as graphs, whose structure is informative of biological function at multiple scales. Simultaneously, omics technologies measure the variation or activity of genes, proteins, or metabolites across individuals or experimental conditions. Integrating the complementary viewpoints of biological networks and omics data is an important task in bioinformatics, but existing methods treat networks as discrete structures, which are intrinsically difficult to integrate with continuous node features or activity measures. Graph neural networks map graph nodes into a low-dimensional vector space representation, and can be trained to preserve both the local graph structure and the similarity between node features. Results We studied the representation of transcriptional, protein–protein and genetic interaction networks in E. coli and mouse using graph neural networks. We found that such representations explain a large proportion of variation in gene expression data, and that using gene expression data as node features improves the reconstruction of the graph from the embedding. We further proposed a new end-to-end Graph Feature Auto-Encoder framework for the prediction of node features utilizing the structure of the gene networks, which is trained on the feature prediction task, and showed that it performs better at predicting unobserved node features than regular MultiLayer Perceptrons. When applied to the problem of imputing missing data in single-cell RNAseq data, the Graph Feature Auto-Encoder utilizing our new graph convolution layer called FeatGraphConv outperformed a state-of-the-art imputation method that does not use protein interaction information, showing the benefit of integrating biological networks and omics data with our proposed approach. Conclusion Our proposed Graph Feature Auto-Encoder framework is a powerful approach for integrating and exploiting the close relation between molecular interaction networks and functional genomics data.

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