GNN-SubNet: disease subnetwork detection with explainable Graph Neural Networks

The tremendous success of graphical neural networks (GNNs) has already had a major impact on systems biology research. For example, GNNs are currently used for drug target recognition in protein-drug interaction networks as well as cancer gene discovery and more. Important aspects whose practical relevance is often underestimated are comprehensibility, interpretability, and explainability. In this work, we present a graph-based deep learning framework for disease subnetwork detection via explainable GNNs. In our framework, each patient is represented by the topology of a protein-protein network (PPI), and the nodes are enriched by molecular multimodal data, such as gene expression and DNA methylation. Therefore, our novel modification of the GNNexplainer for model-wide explanations can detect potential disease subnetworks, which is of high practical relevance. The proposed methods are implemented in the GNN-SubNet Python program, which we have made freely available on our GitHub for the international research community (https://github.com/pievos101/GNN-SubNet).

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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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Graph Neural Networks: Taxonomy, Advances, and Trends

ACM Transactions on Intelligent Systems and Technology ◽

10.1145/3495161 ◽

2022 ◽

Vol 13 (1) ◽

pp. 1-54

Author(s):

Yu Zhou ◽

Haixia Zheng ◽

Xin Huang ◽

Shufeng Hao ◽

Dengao Li ◽

...

Keyword(s):

Neural Networks ◽

Real World ◽

Research Community ◽

Future Research ◽

Research Directions ◽

Comprehensive Review ◽

Future Research Directions ◽

Graph Neural Networks ◽

Low Dimensional

Graph neural networks provide a powerful toolkit for embedding real-world graphs into low-dimensional spaces according to specific tasks. Up to now, there have been several surveys on this topic. However, they usually lay emphasis on different angles so that the readers cannot see a panorama of the graph neural networks. This survey aims to overcome this limitation and provide a systematic and comprehensive review on the graph neural networks. First of all, we provide a novel taxonomy for the graph neural networks, and then refer to up to 327 relevant literatures to show the panorama of the graph neural networks. All of them are classified into the corresponding categories. In order to drive the graph neural networks into a new stage, we summarize four future research directions so as to overcome the challenges faced. It is expected that more and more scholars can understand and exploit the graph neural networks and use them in their research community.

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Estimating latent positions of actors using Neural Networks in R with GCN4R

10.1101/2020.11.02.364935 ◽

2020 ◽

Author(s):

Joshua Levy ◽

Carly Bobak ◽

Brock Christensen ◽

Louis Vaickus ◽

James O’Malley

Keyword(s):

Neural Networks ◽

Deep Learning ◽

Learning Community ◽

Biological Networks ◽

Peer Effects ◽

Prediction Models ◽

Research Community ◽

Social Network Data ◽

Covariate Information ◽

Graph Neural Networks

AbstractNetwork analysis methods are useful to better understand and contextualize relationships between entities. While statistical and machine learning prediction models generally assume independence between actors, network-based statistical methods for social network data allow for dyadic dependence between actors. While numerous methods have been developed for the R statistical software to analyze such data, deep learning methods have not been implemented in this language. Here, we introduce GCN4R, an R library for fitting graph neural networks on independent networks to aggregate actor covariate information to yield meaningful embeddings for a variety of network-based tasks (e.g. community detection, peer effects models, social influence). We provide an extensive overview of insights and methods utilized by the deep learning community on learning on social and biological networks, followed by a tutorial that demonstrates some of the capabilities of the GCN4R framework to make these methods more accessible to the R research community.

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GraphDTA: Predicting drug–target binding affinity with graph neural networks

10.1101/684662 ◽

2019 ◽

Cited By ~ 6

Author(s):

Thin Nguyen ◽

Hang Le ◽

Thomas P. Quinn ◽

Tri Nguyen ◽

Thuc Duy Le ◽

...

Keyword(s):

Neural Networks ◽

Deep Learning ◽

Binding Affinity ◽

Drug Target ◽

Interaction Strength ◽

Drug Repurposing ◽

Learning Models ◽

Link Type ◽

Target Binding ◽

Graph Neural Networks

AbstractThe development of new drugs is costly, time consuming, and often accompanied with safety issues. Drug repurposing can avoid the expensive and lengthy process of drug development by finding new uses for already approved drugs. In order to repurpose drugs effectively, it is useful to know which proteins are targeted by which drugs. Computational models that estimate the interaction strength of new drug--target pairs have the potential to expedite drug repurposing. Several models have been proposed for this task. However, these models represent the drugs as strings, which is not a natural way to represent molecules. We propose a new model called GraphDTA that represents drugs as graphs and uses graph neural networks to predict drug--target affinity. We show that graph neural networks not only predict drug--target affinity better than non-deep learning models, but also outperform competing deep learning methods. Our results confirm that deep learning models are appropriate for drug--target binding affinity prediction, and that representing drugs as graphs can lead to further improvements.Availability of data and materialsThe proposed models are implemented in Python. Related data, pre-trained models, and source code are publicly available at https://github.com/thinng/GraphDTA. All scripts and data needed to reproduce the post-hoc statistical analysis are available from https://doi.org/10.5281/[email protected]

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Learning Multi-Task Communication with Message Passing for Sequence Learning

Proceedings of the AAAI Conference on Artificial Intelligence ◽

10.1609/aaai.v33i01.33014360 ◽

2019 ◽

Vol 33 ◽

pp. 4360-4367 ◽

Cited By ~ 1

Author(s):

Pengfei Liu ◽

Jie Fu ◽

Yue Dong ◽

Xipeng Qiu ◽

Jackie Chi Kit Cheung

Keyword(s):

Neural Networks ◽

Transfer Learning ◽

Text Classification ◽

Sequence Learning ◽

Message Passing ◽

Ad Hoc ◽

General Graph ◽

Learning Framework ◽

Task Learning ◽

Graph Neural Networks

We present two architectures for multi-task learning with neural sequence models. Our approach allows the relationships between different tasks to be learned dynamically, rather than using an ad-hoc pre-defined structure as in previous work. We adopt the idea from message-passing graph neural networks, and propose a general graph multi-task learning framework in which different tasks can communicate with each other in an effective and interpretable way. We conduct extensive experiments in text classification and sequence labelling to evaluate our approach on multi-task learning and transfer learning. The empirical results show that our models not only outperform competitive baselines, but also learn interpretable and transferable patterns across tasks.

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GraphDTA: Predicting drug–target binding affinity with graph neural networks

Bioinformatics ◽

10.1093/bioinformatics/btaa921 ◽

2020 ◽

Author(s):

Thin Nguyen ◽

Hang Le ◽

Thomas P Quinn ◽

Tri Nguyen ◽

Thuc Duy Le ◽

...

Keyword(s):

Neural Networks ◽

Deep Learning ◽

Binding Affinity ◽

Drug Target ◽

Interaction Strength ◽

Drug Repurposing ◽

New Drugs ◽

Learning Models ◽

Target Binding ◽

Graph Neural Networks

Abstract The development of new drugs is costly, time consuming, and often accompanied with safety issues. Drug repurposing can avoid the expensive and lengthy process of drug development by finding new uses for already approved drugs. In order to repurpose drugs effectively, it is useful to know which proteins are targeted by which drugs. Computational models that estimate the interaction strength of new drug–target pairs have the potential to expedite drug repurposing. Several models have been proposed for this task. However, these models represent the drugs as strings, which is not a natural way to represent molecules. We propose a new model called GraphDTA that represents drugs as graphs and uses graph neural networks to predict drug–target affinity. We show that graph neural networks not only predict drug–target affinity better than non-deep learning models, but also outperform competing deep learning methods. Our results confirm that deep learning models are appropriate for drug–target binding affinity prediction, and that representing drugs as graphs can lead to further improvements. Availability of data and materials The proposed models are implemented in Python. Related data, pre-trained models, and source code are publicly available at https://github.com/thinng/GraphDTA. All scripts and data needed to reproduce the post-hoc statistical analysis are available from https://doi.org/10.5281/zenodo.3603523.

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A machine learning framework for predicting drug–drug interactions

Scientific Reports ◽

10.1038/s41598-021-97193-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Suyu Mei ◽

Kun Zhang

Keyword(s):

Machine Learning ◽

Drug Interactions ◽

Drug Target ◽

Target Genes ◽

Protein Interaction Networks ◽

Interaction Networks ◽

Protein Protein Interaction ◽

Learning Framework ◽

Protein Protein Interaction Networks ◽

Statistical Metrics

AbstractUnderstanding drug–drug interactions is an essential step to reduce the risk of adverse drug events before clinical drug co-prescription. Existing methods, commonly integrating heterogeneous data to increase model performance, often suffer from a high model complexity, As such, how to elucidate the molecular mechanisms underlying drug–drug interactions while preserving rational biological interpretability is a challenging task in computational modeling for drug discovery. In this study, we attempt to investigate drug–drug interactions via the associations between genes that two drugs target. For this purpose, we propose a simple f drug target profile representation to depict drugs and drug pairs, from which an l2-regularized logistic regression model is built to predict drug–drug interactions. Furthermore, we define several statistical metrics in the context of human protein–protein interaction networks and signaling pathways to measure the interaction intensity, interaction efficacy and action range between two drugs. Large-scale empirical studies including both cross validation and independent test show that the proposed drug target profiles-based machine learning framework outperforms existing data integration-based methods. The proposed statistical metrics show that two drugs easily interact in the cases that they target common genes; or their target genes connect via short paths in protein–protein interaction networks; or their target genes are located at signaling pathways that have cross-talks. The unravelled mechanisms could provide biological insights into potential adverse drug reactions of co-prescribed drugs.

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Graph Neural Networks for Prediction of Fuel Ignition Quality

10.26434/chemrxiv.12280325.v1 ◽

2020 ◽

Author(s):

Artur Schweidtmann ◽

Jan Rittig ◽

Andrea König ◽

Martin Grohe ◽

Alexander Mitsos ◽

...

Keyword(s):

Neural Networks ◽

Octane Number ◽

Molecular Graph ◽

Chemical Properties ◽

Graph Representation ◽

Structure Property ◽

Oxygenated Hydrocarbons ◽

Physico Chemical ◽

Ignition Quality ◽

Graph Neural Networks

<div>Prediction of combustion-related properties of (oxygenated) hydrocarbons is an important and challenging task for which quantitative structure-property relationship (QSPR) models are frequently employed. Recently, a machine learning method, graph neural networks (GNNs), has shown promising results for the prediction of structure-property relationships. GNNs utilize a graph representation of molecules, where atoms correspond to nodes and bonds to edges containing information about the molecular structure. More specifically, GNNs learn physico-chemical properties as a function of the molecular graph in a supervised learning setup using a backpropagation algorithm. This end-to-end learning approach eliminates the need for selection of molecular descriptors or structural groups, as it learns optimal fingerprints through graph convolutions and maps the fingerprints to the physico-chemical properties by deep learning. We develop GNN models for predicting three fuel ignition quality indicators, i.e., the derived cetane number (DCN), the research octane number (RON), and the motor octane number (MON), of oxygenated and non-oxygenated hydrocarbons. In light of limited experimental data in the order of hundreds, we propose a combination of multi-task learning, transfer learning, and ensemble learning. The results show competitive performance of the proposed GNN approach compared to state-of-the-art QSPR models making it a promising field for future research. The prediction tool is available via a web front-end at www.avt.rwth-aachen.de/gnn.</div>

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