Dataset Information

Predicting genetic interactions, cell line dependencies and drug sensitivities with variational graph auto-encoder.

ABSTRACT: Large scale cancer genomics data provide crucial information about the disease and reveal points of intervention. However, systematic data have been collected in specific cell lines and their collection is laborious and costly. Hence, there is a need to develop computational models that can predict such data for any genomic context of interest. Here we develop novel models that build on variational graph auto-encoders and can integrate diverse types of data to provide high quality predictions of genetic interactions, cell line dependencies and drug sensitivities, outperforming previous methods. Our models, data and implementation are available at: https://github.com/aijag/drugGraphNet.

SUBMITTER: Gervits A

PROVIDER: S-EPMC9755598 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Predicting genetic interactions, cell line dependencies and drug sensitivities with variational graph auto-encoder.

Gervits Asia A Sharan Roded R

Frontiers in bioinformatics 20221202

Large scale cancer genomics data provide crucial information about the disease and reveal points of intervention. However, systematic data have been collected in specific cell lines and their collection is laborious and costly. Hence, there is a need to develop computational models that can predict such data for any genomic context of interest. Here we develop novel models that build on variational graph auto-encoders and can integrate diverse types of data to provide high quality predictions of ...[more]

PMID: 36530386

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Project description:The development of chromatin immunoprecipitation (ChIP) with massively parallel DNA sequencing (ChIP-seq) technologies has promoted generation of large-scale epigenomics data, providing us unprecedented opportunities to explore the landscape of epigenomic profiles at scales across both histone marks and tissue types. In addition to many tools directly for data analysis, advanced computational approaches, such as deep learning, have recently become promising to deeply mine the data structures and identify important regulators from complex functional genomics data. We implemented a neural network framework, a Variational Auto-Encoder (VAE) model, to explore the epigenomic data from the Roadmap Epigenomics Project and the Encyclopedia of DNA Elements (ENCODE) project. Our model is applied to 935 reference samples, covering 28 tissues and 12 histone marks. We used the enhancer and promoter regions as the annotation features and ChIP-seq signal values in these regions as the feature values. Through a parameter sweep process, we identified the suitable hyperparameter values and built a VAE model to represent the epigenomics data and to further explore the biological regulation. The resultant Roadmap-ENCODE VAE (RE-VAE) model contained data compression and feature representation. Using the compressed data in the latent space, we found that the majority of histone marks were well clustered but not for tissues or cell types. Tissue or cell specificity was observed only in some histone marks (e.g., H3K4me3 and H3K27ac) and could be characterized when the number of tissue samples is large (e.g., blood and brain). In blood, the contributive regions and genes identified by RE-VAE model were confirmed by tissue-specificity enrichment analysis with an independent tissue expression panel. Finally, we demonstrated that RE-VAE model could detect cancer cell lines with similar epigenomics profiles. In conclusion, we introduced and implemented a VAE model to represent large-scale epigenomics data. The model could be used to explore classifications of histone modifications and tissue/cell specificity and to classify new data with unknown sources.

Project description:BackgroundMolecular 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.ResultsWe 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.ConclusionOur 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.

Project description:BackgroundLong non-coding RNAs (lncRNAs) can prevent, diagnose, and treat a variety of complex human diseases, and it is crucial to establish a method to efficiently predict lncRNA-disease associations.ResultsIn this paper, we propose a prediction method for the lncRNA-disease association relationship, named LDAGM, which is based on the Graph Convolutional Autoencoder and Multilayer Perceptron model. The method first extracts the functional similarity and Gaussian interaction profile kernel similarity of lncRNAs and miRNAs, as well as the semantic similarity and Gaussian interaction profile kernel similarity of diseases. It then constructs six homogeneous networks and deeply fuses them using a deep topology feature extraction method. The fused networks facilitate feature complementation and deep mining of the original association relationships, capturing the deep connections between nodes. Next, by combining the obtained deep topological features with the similarity network of lncRNA, disease, and miRNA interactions, we construct a multi-view heterogeneous network model. The Graph Convolutional Autoencoder is employed for nonlinear feature extraction. Finally, the extracted nonlinear features are combined with the deep topological features of the multi-view heterogeneous network to obtain the final feature representation of the lncRNA-disease pair. Prediction of the lncRNA-disease association relationship is performed using the Multilayer Perceptron model. To enhance the performance and stability of the Multilayer Perceptron model, we introduce a hidden layer called the aggregation layer in the Multilayer Perceptron model. Through a gate mechanism, it controls the flow of information between each hidden layer in the Multilayer Perceptron model, aiming to achieve optimal feature extraction from each hidden layer.ConclusionsParameter analysis, ablation studies, and comparison experiments verified the effectiveness of this method, and case studies verified the accuracy of this method in predicting lncRNA-disease association relationships.

Dataset Information

Predicting genetic interactions, cell line dependencies and drug sensitivities with variational graph auto-encoder.

Publications

Predicting genetic interactions, cell line dependencies and drug sensitivities with variational graph auto-encoder.

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