scENCORE: leveraging single-cell epigenetic data to predict chromatin conformation using graph embedding.

Dynamic compartmentalization of eukaryotic DNA into active and repressed states enables diverse transcriptional programs to arise from a single genetic blueprint, whereas its dysregulation can be strongly linked to a broad spectrum of diseases. While single-cell Hi-C experiments allow for chromosome conformation profiling across many cells, they are still expensive and not widely available for most labs. Here, we propose an alternate approach, scENCORE, to computationally reconstruct chromatin compartments from the more affordable and widely accessible single-cell epigenetic data. First, scENCORE constructs a long-range epigenetic correlation graph to mimic chromatin interaction frequencies, where nodes and edges represent genome bins and their correlations. Then, it learns the node embeddings to cluster genome regions into A/B compartments and aligns different graphs to quantify chromatin conformation changes across conditions. Benchmarking using cell-type-matched Hi-C experiments demonstrates that scENCORE can robustly reconstruct A/B compartments in a cell-type-specific manner. Furthermore, our chromatin confirmation switching studies highlight substantial compartment-switching events that may introduce substantial regulatory and transcriptional changes in psychiatric disease. In summary, scENCORE allows accurate and cost-effective A/B compartment reconstruction to delineate higher-order chromatin structure heterogeneity in complex tissues.

Spatially contrastive variational autoencoder for deciphering tissue heterogeneity from spatially resolved transcriptomics.

Recent advances in spatially resolved transcriptomics (SRT) have brought ever-increasing opportunities to characterize expression landscape in the context of tissue spatiality. Nevertheless, there still exist multiple challenges to accurately detect spatial functional regions in tissue. Here, we present a novel contrastive learning framework, SPAtially Contrastive variational AutoEncoder (SpaCAE), which contrasts transcriptomic signals of each spot and its spatial neighbors to achieve fine-grained tissue structures detection. By employing a graph embedding variational autoencoder and incorporating a deep contrastive strategy, SpaCAE achieves a balance between spatial local information and global information of expression, enabling effective learning of representations with spatial constraints. Particularly, SpaCAE provides a graph deconvolutional decoder to address the smoothing effect of local spatial structure on expression's self-supervised learning, an aspect often overlooked by current graph neural networks. We demonstrated that SpaCAE could achieve effective performance on SRT data generated from multiple technologies for spatial domains identification and data denoising, making it a remarkable tool to obtain novel insights from SRT studies.

SEGCECO: Subgraph Embedding of Gene expression matrix for prediction of CEll-cell COmmunication.

Recent advances in single-cell RNA sequencing technology have eased analyses of signaling networks of cells. Recently, cell-cell interaction has been studied based on various link prediction approaches on graph-structured data. These approaches have assumptions about the likelihood of node interaction, thus showing high performance for only some specific networks. Subgraph-based methods have solved this problem and outperformed other approaches by extracting local subgraphs from a given network. In this work, we present a novel method, called Subgraph Embedding of Gene expression matrix for prediction of CEll-cell COmmunication (SEGCECO), which uses an attributed graph convolutional neural network to predict cell-cell communication from single-cell RNA-seq data. SEGCECO captures the latent and explicit attributes of undirected, attributed graphs constructed from the gene expression profile of individual cells. High-dimensional and sparse single-cell RNA-seq data make converting the data into a graphical format a daunting task. We successfully overcome this limitation by applying SoptSC, a similarity-based optimization method in which the cell-cell communication network is built using a cell-cell similarity matrix which is learned from gene expression data. We performed experiments on six datasets extracted from the human and mouse pancreas tissue. Our comparative analysis shows that SEGCECO outperforms latent feature-based approaches, and the state-of-the-art method for link prediction, WLNM, with 0.99 ROC and 99% prediction accuracy. The datasets can be found at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE84133 and the code is publicly available at Github https://github.com/sheenahora/SEGCECO and Code Ocean https://codeocean.com/capsule/8244724/tree.

DeepFGRN: inference of gene regulatory network with regulation type based on directed graph embedding.

The inference of gene regulatory networks (GRNs) from gene expression profiles has been a key issue in systems biology, prompting many researchers to develop diverse computational methods. However, most of these methods do not reconstruct directed GRNs with regulatory types because of the lack of benchmark datasets or defects in the computational methods. Here, we collect benchmark datasets and propose a deep learning-based model, DeepFGRN, for reconstructing fine gene regulatory networks (FGRNs) with both regulation types and directions. In addition, the GRNs of real species are always large graphs with direction and high sparsity, which impede the advancement of GRN inference. Therefore, DeepFGRN builds a node bidirectional representation module to capture the directed graph embedding representation of the GRN. Specifically, the source and target generators are designed to learn the low-dimensional dense embedding of the source and target neighbors of a gene, respectively. An adversarial learning strategy is applied to iteratively learn the real neighbors of each gene. In addition, because the expression profiles of genes with regulatory associations are correlative, a correlation analysis module is designed. Specifically, this module not only fully extracts gene expression features, but also captures the correlation between regulators and target genes. Experimental results show that DeepFGRN has a competitive capability for both GRN and FGRN inference. Potential biomarkers and therapeutic drugs for breast cancer, liver cancer, lung cancer and coronavirus disease 2019 are identified based on the candidate FGRNs, providing a possible opportunity to advance our knowledge of disease treatments.

HyGAnno: hybrid graph neural network-based cell type annotation for single-cell ATAC sequencing data.

Reliable cell type annotations are crucial for investigating cellular heterogeneity in single-cell omics data. Although various computational approaches have been proposed for single-cell RNA sequencing (scRNA-seq) annotation, high-quality cell labels are still lacking in single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) data, because of extreme sparsity and inconsistent chromatin accessibility between datasets. Here, we present a novel automated cell annotation method that transfers cell type information from a well-labeled scRNA-seq reference to an unlabeled scATAC-seq target, via a parallel graph neural network, in a semi-supervised manner. Unlike existing methods that utilize only gene expression or gene activity features, HyGAnno leverages genome-wide accessibility peak features to facilitate the training process. In addition, HyGAnno reconstructs a reference-target cell graph to detect cells with low prediction reliability, according to their specific graph connectivity patterns. HyGAnno was assessed across various datasets, showcasing its strengths in precise cell annotation, generating interpretable cell embeddings, robustness to noisy reference data and adaptability to tumor tissues.

EGPDI: identifying protein-DNA binding sites based on multi-view graph embedding fusion.

Mechanisms of protein-DNA interactions are involved in a wide range of biological activities and processes. Accurately identifying binding sites between proteins and DNA is crucial for analyzing genetic material, exploring protein functions, and designing novel drugs. In recent years, several computational methods have been proposed as alternatives to time-consuming and expensive traditional experiments. However, accurately predicting protein-DNA binding sites still remains a challenge. Existing computational methods often rely on handcrafted features and a single-model architecture, leaving room for improvement. We propose a novel computational method, called EGPDI, based on multi-view graph embedding fusion. This approach involves the integration of Equivariant Graph Neural Networks (EGNN) and Graph Convolutional Networks II (GCNII), independently configured to profoundly mine the global and local node embedding representations. An advanced gated multi-head attention mechanism is subsequently employed to capture the attention weights of the dual embedding representations, thereby facilitating the integration of node features. Besides, extra node features from protein language models are introduced to provide more structural information. To our knowledge, this is the first time that multi-view graph embedding fusion has been applied to the task of protein-DNA binding site prediction. The results of five-fold cross-validation and independent testing demonstrate that EGPDI outperforms state-of-the-art methods. Further comparative experiments and case studies also verify the superiority and generalization ability of EGPDI.

HNSPPI: a hybrid computational model combing network and sequence information for predicting protein-protein interaction.

Most life activities in organisms are regulated through protein complexes, which are mainly controlled via Protein-Protein Interactions (PPIs). Discovering new interactions between proteins and revealing their biological functions are of great significance for understanding the molecular mechanisms of biological processes and identifying the potential targets in drug discovery. Current experimental methods only capture stable protein interactions, which lead to limited coverage. In addition, expensive cost and time consuming are also the obvious shortcomings. In recent years, various computational methods have been successfully developed for predicting PPIs based only on protein homology, primary sequences of protein or gene ontology information. Computational efficiency and data complexity are still the main bottlenecks for the algorithm generalization. In this study, we proposed a novel computational framework, HNSPPI, to predict PPIs. As a hybrid supervised learning model, HNSPPI comprehensively characterizes the intrinsic relationship between two proteins by integrating amino acid sequence information and connection properties of PPI network. The experimental results show that HNSPPI works very well on six benchmark datasets. Moreover, the comparison analysis proved that our model significantly outperforms other five existing algorithms. Finally, we used the HNSPPI model to explore the SARS-CoV-2-Human interaction system and found several potential regulations. In summary, HNSPPI is a promising model for predicting new protein interactions from known PPI data.

A systematic assessment of deep learning methods for drug response prediction: from in vitro to clinical applications.

Drug response prediction is an important problem in personalized cancer therapy. Among various newly developed models, significant improvement in prediction performance has been reported using deep learning methods. However, systematic comparisons of deep learning methods, especially of the transferability from preclinical models to clinical cohorts, are currently lacking. To provide a more rigorous assessment, the performance of six representative deep learning methods for drug response prediction using nine evaluation metrics, including the overall prediction accuracy, predictability of each drug, potential associated factors and transferability to clinical cohorts, in multiple application scenarios was benchmarked. Most methods show promising prediction within cell line datasets, and TGSA, with its lower time cost and better performance, is recommended. Although the performance metrics decrease when applying models trained on cell lines to patients, a certain amount of power to distinguish clinical response on some drugs can be maintained using CRDNN and TGSA. With these assessments, we provide a guidance for researchers to choose appropriate methods, as well as insights into future directions for the development of more effective methods in clinical scenarios.

Graph embedding on mass spectrometry- and sequencing-based biomedical data.

Graph embedding techniques are using deep learning algorithms in data analysis to solve problems of such as node classification, link prediction, community detection, and visualization. Although typically used in the context of guessing friendships in social media, several applications for graph embedding techniques in biomedical data analysis have emerged. While these approaches remain computationally demanding, several developments over the last years facilitate their application to study biomedical data and thus may help advance biological discoveries. Therefore, in this review, we discuss the principles of graph embedding techniques and explore the usefulness for understanding biological network data derived from mass spectrometry and sequencing experiments, the current workhorses of systems biology studies. In particular, we focus on recent examples for characterizing protein-protein interaction networks and predicting novel drug functions.

DNI-MDCAP: improvement of causal MiRNA-disease association prediction based on deep network imputation.

BACKGROUND: MiRNAs are involved in the occurrence and development of many diseases. Extensive literature studies have demonstrated that miRNA-disease associations are stratified and encompass ~ 20% causal associations. Computational models that predict causal miRNA-disease associations provide effective guidance in identifying novel interpretations of disease mechanisms and potential therapeutic targets. Although several predictive models for miRNA-disease associations exist, it is still challenging to discriminate causal miRNA-disease associations from non-causal ones. Hence, there is a pressing need to develop an efficient prediction model for causal miRNA-disease association prediction. RESULTS: We developed DNI-MDCAP, an improved computational model that incorporated additional miRNA similarity metrics, deep graph embedding learning-based network imputation and semi-supervised learning framework. Through extensive predictive performance evaluation, including tenfold cross-validation and independent test, DNI-MDCAP showed excellent performance in identifying causal miRNA-disease associations, achieving an area under the receiver operating characteristic curve (AUROC) of 0.896 and 0.889, respectively. Regarding the challenge of discriminating causal miRNA-disease associations from non-causal ones, DNI-MDCAP exhibited superior predictive performance compared to existing models MDCAP and LE-MDCAP, reaching an AUROC of 0.870. Wilcoxon test also indicated significantly higher prediction scores for causal associations than for non-causal ones. Finally, the potential causal miRNA-disease associations predicted by DNI-MDCAP, exemplified by diabetic nephropathies and hsa-miR-193a, have been validated by recently published literature, further supporting the reliability of the prediction model. CONCLUSIONS: DNI-MDCAP is a dedicated tool to specifically distinguish causal miRNA-disease associations with substantially improved accuracy. DNI-MDCAP is freely accessible at http://www.rnanut.net/DNIMDCAP/ .

MGEGFP: a multi-view graph embedding method for gene function prediction based on adaptive estimation with GCN.

In recent years, a number of computational approaches have been proposed to effectively integrate multiple heterogeneous biological networks, and have shown impressive performance for inferring gene function. However, the previous methods do not fully represent the critical neighborhood relationship between genes during the feature learning process. Furthermore, it is difficult to accurately estimate the contributions of different views for multi-view integration. In this paper, we propose MGEGFP, a multi-view graph embedding method based on adaptive estimation with Graph Convolutional Network (GCN), to learn high-quality gene representations among multiple interaction networks for function prediction. First, we design a dual-channel GCN encoder to disentangle the view-specific information and the consensus pattern across diverse networks. By the aid of disentangled representations, we develop a multi-gate module to adaptively estimate the contributions of different views during each reconstruction process and make full use of the multiplexity advantages, where a diversity preservation constraint is designed to prevent the over-fitting problem. To validate the effectiveness of our model, we conduct experiments on networks from the STRING database for both yeast and human datasets, and compare the performance with seven state-of-the-art methods in five evaluation metrics. Moreover, the ablation study manifests the important contribution of the designed dual-channel encoder, multi-gate module and the diversity preservation constraint in MGEGFP. The experimental results confirm the superiority of our proposed method and suggest that MGEGFP can be a useful tool for gene function prediction.

GE-Impute: graph embedding-based imputation for single-cell RNA-seq data.

Single-cell RNA-sequencing (scRNA-seq) has been widely used to depict gene expression profiles at the single-cell resolution. However, its relatively high dropout rate often results in artificial zero expressions of genes and therefore compromised reliability of results. To overcome such unwanted sparsity of scRNA-seq data, several imputation algorithms have been developed to recover the single-cell expression profiles. Here, we propose a novel approach, GE-Impute, to impute the dropout zeros in scRNA-seq data with graph embedding-based neural network model. GE-Impute learns the neural graph representation for each cell and reconstructs the cell-cell similarity network accordingly, which enables better imputation of dropout zeros based on the more accurately allocated neighbors in the similarity network. Gene expression correlation analysis between true expression data and simulated dropout data suggests significantly better performance of GE-Impute on recovering dropout zeros for both droplet- and plated-based scRNA-seq data. GE-Impute also outperforms other imputation methods in identifying differentially expressed genes and improving the unsupervised clustering on datasets from various scRNA-seq techniques. Moreover, GE-Impute enhances the identification of marker genes, facilitating the cell type assignment of clusters. In trajectory analysis, GE-Impute improves time-course scRNA-seq data analysis and reconstructing differentiation trajectory. The above results together demonstrate that GE-Impute could be a useful method to recover the single-cell expression profiles, thus enabling better biological interpretation of scRNA-seq data. GE-Impute is implemented in Python and is freely available at https://github.com/wxbCaterpillar/GE-Impute.

Ensembles of knowledge graph embedding models improve predictions for drug discovery.

Recent advances in Knowledge Graphs (KGs) and Knowledge Graph Embedding Models (KGEMs) have led to their adoption in a broad range of fields and applications. The current publishing system in machine learning requires newly introduced KGEMs to achieve state-of-the-art performance, surpassing at least one benchmark in order to be published. Despite this, dozens of novel architectures are published every year, making it challenging for users, even within the field, to deduce the most suitable configuration for a given application. A typical biomedical application of KGEMs is drug-disease prediction in the context of drug discovery, in which a KGEM is trained to predict triples linking drugs and diseases. These predictions can be later tested in clinical trials following extensive experimental validation. However, given the infeasibility of evaluating each of these predictions and that only a minimal number of candidates can be experimentally tested, models that yield higher precision on the top prioritized triples are preferred. In this paper, we apply the concept of ensemble learning on KGEMs for drug discovery to assess whether combining the predictions of several models can lead to an overall improvement in predictive performance. First, we trained and benchmarked 10 KGEMs to predict drug-disease triples on two independent biomedical KGs designed for drug discovery. Following, we applied different ensemble methods that aggregate the predictions of these models by leveraging the distribution or the position of the predicted triple scores. We then demonstrate how the ensemble models can achieve better results than the original KGEMs by benchmarking the precision (i.e., number of true positives prioritized) of their top predictions. Lastly, we released the source code presented in this work at https://github.com/enveda/kgem-ensembles-in-drug-discovery.

Graph representation learning in bioinformatics: trends, methods and applications.

Graph is a natural data structure for describing complex systems, which contains a set of objects and relationships. Ubiquitous real-life biomedical problems can be modeled as graph analytics tasks. Machine learning, especially deep learning, succeeds in vast bioinformatics scenarios with data represented in Euclidean domain. However, rich relational information between biological elements is retained in the non-Euclidean biomedical graphs, which is not learning friendly to classic machine learning methods. Graph representation learning aims to embed graph into a low-dimensional space while preserving graph topology and node properties. It bridges biomedical graphs and modern machine learning methods and has recently raised widespread interest in both machine learning and bioinformatics communities. In this work, we summarize the advances of graph representation learning and its representative applications in bioinformatics. To provide a comprehensive and structured analysis and perspective, we first categorize and analyze both graph embedding methods (homogeneous graph embedding, heterogeneous graph embedding, attribute graph embedding) and graph neural networks. Furthermore, we summarize their representative applications from molecular level to genomics, pharmaceutical and healthcare systems level. Moreover, we provide open resource platforms and libraries for implementing these graph representation learning methods and discuss the challenges and opportunities of graph representation learning in bioinformatics. This work provides a comprehensive survey of emerging graph representation learning algorithms and their applications in bioinformatics. It is anticipated that it could bring valuable insights for researchers to contribute their knowledge to graph representation learning and future-oriented bioinformatics studies.

ATENA: A Web-Based Tool for Modelling Metal Oxide Nanoparticles Based on NanoFingerprint Quantitative Structure-Activity Relationships.

Modelling size-realistic nanomaterials to analyse some of their properties, such as toxicity, solubility, or electronic structure, is a current challenge in computational and theoretical chemistry. The representation of the all-atom three-dimensional structure of a nanocompound would be ideal, as it could account explicitly for structural effects. However, the use of the whole structure is tedious due to the high data management and the structural complexity that accompanies the surface of the nanoparticle. Developing appropriate tools that enable a quantitative analysis of the structure, as well as the selection of regions of interest such as the core-shell, is a crucial step toward enabling the efficient analysis and processing of model nanostructures. The aim of this study was twofold. First, we defined the NanoFingerprint, which is a representation of a nanocompound in the form of a vector based on its 3D structure. The local relationship between atoms, i.e., their coordination within successive layers of neighbours, allows the characterisation of the local structure through the atom connectivity, maintaining the information of the three-dimensional structure but increasing the management ability. Second, we present a web server, called ATENA, to generate NanoFingerprints and other tools based on the 3D structure of the nanocompounds. A case study is reported to show the validity of our new fingerprint tool and the usefulness of our server. The scientific community and also private companies have a new tool based on a public web server for exploring the toxicity of nanocompounds.

A Personalized Collaborative Filtering Recommendation System Based on Bi-Graph Embedding and Causal Reasoning.

The integration of graph embedding technology and collaborative filtering algorithms has shown promise in enhancing the performance of recommendation systems. However, existing integrated recommendation algorithms often suffer from feature bias and lack effectiveness in personalized user recommendation. For instance, users' historical interactions with a certain class of items may inaccurately lead to recommendations of all items within that class, resulting in feature bias. Moreover, accommodating changes in user interests over time poses a significant challenge. This study introduces a novel recommendation model, RCKFM, which addresses these shortcomings by leveraging the CoFM model, TransR graph embedding model, backdoor tuning of causal inference, KL divergence, and the factorization machine model. RCKFM focuses on improving graph embedding technology, adjusting feature bias in embedding models, and achieving personalized recommendations. Specifically, it employs the TransR graph embedding model to handle various relationship types effectively, mitigates feature bias using causal inference techniques, and predicts changes in user interests through KL divergence, thereby enhancing the accuracy of personalized recommendations. Experimental evaluations conducted on publicly available datasets, including "MovieLens-1M" and "Douban dataset" from Kaggle, demonstrate the superior performance of the RCKFM model. The results indicate a significant improvement of between 3.17% and 6.81% in key indicators such as precision, recall, normalized discount cumulative gain, and hit rate in the top-10 recommendation tasks. These findings underscore the efficacy and potential impact of the proposed RCKFM model in advancing recommendation systems.

DrugRep-HeSiaGraph: when heterogenous siamese neural network meets knowledge graphs for drug repurposing.

BACKGROUND: Drug repurposing is an approach that holds promise for identifying new therapeutic uses for existing drugs. Recently, knowledge graphs have emerged as significant tools for addressing the challenges of drug repurposing. However, there are still major issues with constructing and embedding knowledge graphs. RESULTS: This study proposes a two-step method called DrugRep-HeSiaGraph to address these challenges. The method integrates the drug-disease knowledge graph with the application of a heterogeneous siamese neural network. In the first step, a drug-disease knowledge graph named DDKG-V1 is constructed by defining new relationship types, and then numerical vector representations for the nodes are created using the distributional learning method. In the second step, a heterogeneous siamese neural network called HeSiaNet is applied to enrich the embedding of drugs and diseases by bringing them closer in a new unified latent space. Then, it predicts potential drug candidates for diseases. DrugRep-HeSiaGraph achieves impressive performance metrics, including an AUC-ROC of 91.16%, an AUC-PR of 90.32%, an accuracy of 84.63%, a BS of 0.119, and an MCC of 69.31%. CONCLUSION: We demonstrate the effectiveness of the proposed method in identifying potential drugs for COVID-19 as a case study. In addition, this study shows the role of dipeptidyl peptidase 4 (DPP-4) as a potential receptor for SARS-CoV-2 and the effectiveness of DPP-4 inhibitors in facing COVID-19. This highlights the practical application of the model in addressing real-world challenges in the field of drug repurposing. The code and data for DrugRep-HeSiaGraph are publicly available at https://github.com/CBRC-lab/DrugRep-HeSiaGraph .

Advancing drug-target interaction prediction: a comprehensive graph-based approach integrating knowledge graph embedding and ProtBert pretraining.

BACKGROUND: The pharmaceutical field faces a significant challenge in validating drug target interactions (DTIs) due to the time and cost involved, leading to only a fraction being experimentally verified. To expedite drug discovery, accurate computational methods are essential for predicting potential interactions. Recently, machine learning techniques, particularly graph-based methods, have gained prominence. These methods utilize networks of drugs and targets, employing knowledge graph embedding (KGE) to represent structured information from knowledge graphs in a continuous vector space. This phenomenon highlights the growing inclination to utilize graph topologies as a means to improve the precision of predicting DTIs, hence addressing the pressing requirement for effective computational methodologies in the field of drug discovery. RESULTS: The present study presents a novel approach called DTIOG for the prediction of DTIs. The methodology employed in this study involves the utilization of a KGE strategy, together with the incorporation of contextual information obtained from protein sequences. More specifically, the study makes use of Protein Bidirectional Encoder Representations from Transformers (ProtBERT) for this purpose. DTIOG utilizes a two-step process to compute embedding vectors using KGE techniques. Additionally, it employs ProtBERT to determine target-target similarity. Different similarity measures, such as Cosine similarity or Euclidean distance, are utilized in the prediction procedure. In addition to the contextual embedding, the proposed unique approach incorporates local representations obtained from the Simplified Molecular Input Line Entry Specification (SMILES) of drugs and the amino acid sequences of protein targets. CONCLUSIONS: The effectiveness of the proposed approach was assessed through extensive experimentation on datasets pertaining to Enzymes, Ion Channels, and G-protein-coupled Receptors. The remarkable efficacy of DTIOG was showcased through the utilization of diverse similarity measures in order to calculate the similarities between drugs and targets. The combination of these factors, along with the incorporation of various classifiers, enabled the model to outperform existing algorithms in its ability to predict DTIs. The consistent observation of this advantage across all datasets underlines the robustness and accuracy of DTIOG in the domain of DTIs. Additionally, our case study suggests that the DTIOG can serve as a valuable tool for discovering new DTIs.

Drug-target prediction utilizing heterogeneous bio-linked network embeddings.

To enable modularization for network-based prediction, we conducted a review of known methods conducting the various subtasks corresponding to the creation of a drug-target prediction framework and associated benchmarking to determine the highest-performing approaches. Accordingly, our contributions are as follows: (i) from a network perspective, we benchmarked the association-mining performance of 32 distinct subnetwork permutations, arranging based on a comprehensive heterogeneous biomedical network derived from 12 repositories; (ii) from a methodological perspective, we identified the best prediction strategy based on a review of combinations of the components with off-the-shelf classification, inference methods and graph embedding methods. Our benchmarking strategy consisted of two series of experiments, totaling six distinct tasks from the two perspectives, to determine the best prediction. We demonstrated that the proposed method outperformed the existing network-based methods as well as how combinatorial networks and methodologies can influence the prediction. In addition, we conducted disease-specific prediction tasks for 20 distinct diseases and showed the reliability of the strategy in predicting 75 novel drug-target associations as shown by a validation utilizing DrugBank 5.1.0. In particular, we revealed a connection of the network topology with the biological explanations for predicting the diseases, 'Asthma' 'Hypertension', and 'Dementia'. The results of our benchmarking produced knowledge on a network-based prediction framework with the modularization of the feature selection and association prediction, which can be easily adapted and extended to other feature sources or machine learning algorithms as well as a performed baseline to comprehensively evaluate the utility of incorporating varying data sources.

MeSHHeading2vec: a new method for representing MeSH headings as vectors based on graph embedding algorithm.

Effectively representing Medical Subject Headings (MeSH) headings (terms) such as disease and drug as discriminative vectors could greatly improve the performance of downstream computational prediction models. However, these terms are often abstract and difficult to quantify. In this paper, we converted the MeSH tree structure into a relationship network and applied several graph embedding algorithms on it to represent these terms. Specifically, the relationship network consisting of nodes (MeSH headings) and edges (relationships), which can be constructed by the tree num. Then, five graph embedding algorithms including DeepWalk, LINE, SDNE, LAP and HOPE were implemented on the relationship network to represent MeSH headings as vectors. In order to evaluate the performance of the proposed methods, we carried out the node classification and relationship prediction tasks. The results show that the MeSH headings characterized by graph embedding algorithms can not only be treated as an independent carrier for representation, but also can be utilized as additional information to enhance the representation ability of vectors. Thus, it can serve as an input and continue to play a significant role in any computational models related to disease, drug, microbe, etc. Besides, our method holds great hope to inspire relevant researchers to study the representation of terms in this network perspective.