Target identification among known drugs by deep learning from heterogeneous networks.
Ontology highlight
ABSTRACT:
SUBMITTER: Zeng X
PROVIDER: S-EPMC8150105 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Motivation:A heterogeneous network topology possessing abundant interactions between biomedical entities has yet to be utilized in similarity-based methods for predicting drug-target associations based on the array of varying features of drugs and their targets. Deep learning reveals features of vertices of a large network that can be adapted in accommodating the similarity-based solutions to provide a flexible method of drug-target prediction. Results:We propose a similarity-based drug-target prediction method that enhances existing association discovery methods by using a topology-based similarity measure. DeepWalk, a deep learning method, is adopted in this study to calculate the similarities within Linked Tripartite Network (LTN), a heterogeneous network generated from biomedical linked datasets. This proposed method shows promising results for drug-target association prediction: 98.96% AUC ROC score with a 10-fold cross-validation and 99.25% AUC ROC score with a Monte Carlo cross-validation with LTN. By utilizing DeepWalk, we demonstrate that: (i) this method outperforms other existing topology-based similarity computation methods, (ii) the performance is better for tripartite than with bipartite networks and (iii) the measure of similarity using network topology outperforms the ones derived from chemical structure (drugs) or genomic sequence (targets). Our proposed methodology proves to be capable of providing a promising solution for drug-target prediction based on topological similarity with a heterogeneous network, and may be readily re-purposed and adapted in the existing of similarity-based methodologies. Availability and Implementation:The proposed method has been developed in JAVA and it is available, along with the data at the following URL: https://github.com/zongnansu1982/drug-target-prediction . Contact:nazong@ucsd.edu. Supplementary information:Supplementary data are available at Bioinformatics online.
| S-EPMC5860112 | biostudies-literature
Project description:Recent studies have demonstrated that the excessive inflammatory response is an important factor of death in coronavirus disease 2019 (COVID-19) patients. In this study, we propose a deep representation on heterogeneous drug networks, termed DeepR2cov, to discover potential agents for treating the excessive inflammatory response in COVID-19 patients. This work explores the multi-hub characteristic of a heterogeneous drug network integrating eight unique networks. Inspired by the multi-hub characteristic, we design 3 billion special meta paths to train a deep representation model for learning low-dimensional vectors that integrate long-range structure dependency and complex semantic relation among network nodes. Based on the representation vectors and transcriptomics data, we predict 22 drugs that bind to tumor necrosis factor-α or interleukin-6, whose therapeutic associations with the inflammation storm in COVID-19 patients, and molecular binding model are further validated via data from PubMed publications, ongoing clinical trials and a docking program. In addition, the results on five biomedical applications suggest that DeepR2cov significantly outperforms five existing representation approaches. In summary, DeepR2cov is a powerful network representation approach and holds the potential to accelerate treatment of the inflammatory responses in COVID-19 patients. The source code and data can be downloaded from https://github.com/pengsl-lab/DeepR2cov.git.
| S-EPMC8344611 | biostudies-literature
Project description:BackgroundOsteoarthritis (OA) is a multifactorial, hypertrophic, and degenerative condition involving the whole joint and affecting a high percentage of middle-aged people. It is due to a combination of factors, although the pivotal mechanisms underlying the disease are still obscure. Moreover, current treatments are still poorly effective, and patients experience a painful and degenerative disease course.MethodsWe used an integrative approach that led us to extract a consensus signature from a meta-analysis of three different OA cohorts. We performed a network-based drug prioritization to detect the most relevant drugs targeting these genes and validated in vitro the most promising candidates. We also proposed a risk score based on a minimal set of genes to predict the OA clinical stage from RNA-Seq data.ResultsWe derived a consensus signature of 44 genes that we validated on an independent dataset. Using network analysis, we identified Resveratrol, Tenoxicam, Benzbromarone, Pirinixic Acid, and Mesalazine as putative drugs of interest for therapeutics in OA for anti-inflammatory properties. We also derived a list of seven gene-targets validated with functional RT-qPCR assays, confirming the in silico predictions. Finally, we identified a predictive subset of genes composed of DNER, TNFSF11, THBS3, LOXL3, TSPAN2, DYSF, ASPN and HTRA1 to compute the patient's risk score. We validated this risk score on an independent dataset with a high AUC (0.875) and compared it with the same approach computed using the entire consensus signature (AUC 0.922).ConclusionsThe consensus signature highlights crucial mechanisms for disease progression. Moreover, these genes were associated with several candidate drugs that could represent potential innovative therapeutics. Furthermore, the patient's risk scores can be used in clinical settings.
| S-EPMC10941480 | biostudies-literature
Project description:We explore heat transport properties of turbulent Rayleigh-Bénard convection in horizontally extended systems by using deep-learning algorithms that greatly reduce the number of degrees of freedom. Particular attention is paid to the slowly evolving turbulent superstructures-so called because they are larger in extent than the height of the convection layer-which appear as temporal patterns of ridges of hot upwelling and cold downwelling fluid, including defects where the ridges merge or end. The machine-learning algorithm trains a deep convolutional neural network (CNN) with U-shaped architecture, consisting of a contraction and a subsequent expansion branch, to reduce the complex 3D turbulent superstructure to a temporal planar network in the midplane of the layer. This results in a data compression by more than five orders of magnitude at the highest Rayleigh number, and its application yields a discrete transport network with dynamically varying defect points, including points of locally enhanced heat flux or "hot spots." One conclusion is that the fraction of heat transport by the superstructure decreases as the Rayleigh number increases (although they might remain individually strong), correspondingly implying the increased importance of small-scale background turbulence.
| S-EPMC6500159 | biostudies-literature
Project description:BACKGROUND:Identifying targets of herbs is a primary step for investigating pharmacological mechanisms of herbal drugs in Traditional Chinese medicine (TCM). Experimental targets identification of herbs is a difficult and time-consuming work. Computational method for identifying herb targets is an efficient approach. However, how to make full use of heterogeneous network data about herbs and targets to improve the performance of herb targets prediction is still a dilemma. METHODS:In our study, a random walk algorithm on the heterogeneous herb-target network (named heNetRW) has been proposed to identify protein targets of herbs. By building a heterogeneous herb-target network involving herbs, targets and their interactions and simulating random walk algorithm on the network, the candidate targets of the given herb can be predicted. RESULTS:The experimental results on large-scale dataset showed that heNetRW had higher performance of targets prediction than PRINCE (improved F1-score by 0.08 and Hit@1 by 21.34% in one validation setting, and improved F1-score by 0.54 and Hit@1 by 69.08% in the other validation setting). Furthermore, we evaluated novel candidate targets of two herbs (rhizoma coptidis and turmeric), which showed our approach could generate potential targets that are valuable for further experimental investigations. CONCLUSIONS:Compared with PRINCE algorithm, heNetRW algorithm can fuse more known information (such as, known herb-target associations and pathway-based similarities of protein pairs) to improve prediction performance. Experimental results also indicated heNetRW had higher performance than PRINCE. The prediction results not only can be used to guide the selection of candidate targets of herbs, but also help to reveal the molecule mechanisms of herbal drugs.
| S-EPMC5872392 | biostudies-literature
Project description:Heterogeneous information networks (HINs) are ubiquitous in real-world applications. Due to the heterogeneity in HINs, the typed edges may not fully align with each other. In order to capture the semantic subtlety, we propose the concept of aspects with each aspect being a unit representing one underlying semantic facet. Meanwhile, network embedding has emerged as a powerful method for learning network representation, where the learned embedding can be used as features in various downstream applications. Therefore, we are motivated to propose a novel embedding learning framework-ASPEM-to preserve the semantic information in HINs based on multiple aspects. Instead of preserving information of the network in one semantic space, ASPEM encapsulates information regarding each aspect individually. In order to select aspects for embedding purpose, we further devise a solution for ASPEM based on dataset-wide statistics. To corroborate the efficacy of ASPEM, we conducted experiments on two real-words datasets with two types of applications-classification and link prediction. Experiment results demonstrate that ASPEM can outperform baseline network embedding learning methods by considering multiple aspects, where the aspects can be selected from the given HIN in an unsupervised manner.
| S-EPMC6135265 | biostudies-literature
Project description:BACKGROUND: Drug addiction is a complex and chronic mental disease, which places a large burden on the American healthcare system due to its negative effects on patients and their families. Recently, network pharmacology is emerging as a promising approach to drug discovery by integrating network biology and polypharmacology, allowing for a deeper understanding of molecular mechanisms of drug actions at the systems level. This study seeks to apply this approach for investigation of illicit drugs and their targets in order to elucidate their interaction patterns and potential secondary drugs that can aid future research and clinical care. RESULTS: In this study, we extracted 188 illicit substances and their related information from the DrugBank database. The data process revealed 86 illicit drugs targeting a total of 73 unique human genes, which forms an illicit drug-target network. Compared to the full drug-target network from DrugBank, illicit drugs and their target genes tend to cluster together and form four subnetworks, corresponding to four major medication categories: depressants, stimulants, analgesics, and steroids. External analysis of Anatomical Therapeutic Chemical (ATC) second sublevel classifications confirmed that the illicit drugs have neurological functions or act via mechanisms of stimulants, opioids, and steroids. To further explore other drugs potentially having associations with illicit drugs, we constructed an illicit-extended drug-target network by adding the drugs that have the same target(s) as illicit drugs to the illicit drug-target network. After analyzing the degree and betweenness of the network, we identified hubs and bridge nodes, which might play important roles in the development and treatment of drug addiction. Among them, 49 non-illicit drugs might have potential to be used to treat addiction or have addictive effects, including some results that are supported by previous studies. CONCLUSIONS: This study presents the first systematic review of the network characteristics of illicit drugs, their targets, and other drugs that share the targets of these illicit drugs. The results, though preliminary, provide some novel insights into the molecular mechanisms of drug addiction. The observation of illicit-related drugs, with partial verification from previous studies, demonstrated that the network-assisted approach is promising for the identification of drug repositioning.
| S-EPMC3849475 | biostudies-literature
Project description:In the near future, value streams associated with Industry 4.0 will be formed by interconnected cyber-physical elements forming complex networks that generate huge amounts of data in real time. The success or failure of industry leaders interested in the continuous improvement of lean management systems in this context is determined by their ability to recognize behavioral patterns in these big data structured within non-Euclidean domains, such as these dynamic sociotechnical complex networks. We assume that artificial intelligence in general and deep learning in particular may be able to help find useful patterns of behavior in 4.0 industrial environments in the lean management of cyber-physical systems. However, although these technologies have meant a paradigm shift in the resolution of complex problems in the past, the traditional methods of deep learning, focused on image or video analysis, both with regular structures, are not able to help in this specific field. This is why this work focuses on proposing geometric deep lean learning, a mathematical methodology that describes deep-lean-learning operations such as convolution and pooling on cyber-physical Industry 4.0 graphs. Geometric deep lean learning is expected to positively support sustainable organizational growth because customers and suppliers ought to be able to reach new levels of transparency and traceability on the quality and efficiency of processes that generate new business for both, hence generating new products, services, and cooperation opportunities in a cyber-physical environment.
| S-EPMC7038400 | biostudies-literature
Project description:We developed a semi-supervised deep learning framework for the identification of doublets in scRNA-seq analysis called Solo. To validate our method, we used MULTI-seq, cholesterol modified oligos (CMOs), to experimentally identify doublets in a solid tissue with diverse cell types, mouse kidney, and showed Solo recapitulated experimentally identified doublets.
2019-11-13 | GSE140262 | GEO
Project description:Applying network science approaches to investigate the functions and anatomy of the human brain is prevalent in modern medical imaging analysis. Due to the complex network topology, for an individual brain, mining a discriminative network representation from the multimodal brain networks is non-trivial. The recent success of deep learning techniques on graph-structured data suggests a new way to model the non-linear cross-modality relationship. However, current deep brain network methods either ignore the intrinsic graph topology or require a network basis shared within a group. To address these challenges, we propose a novel end-to-end deep graph representation learning (Deep Multimodal Brain Networks - DMBN) to fuse multimodal brain networks. Specifically, we decipher the cross-modality relationship through a graph encoding and decoding process. The higher-order network mappings from brain structural networks to functional networks are learned in the node domain. The learned network representation is a set of node features that are informative to induce brain saliency maps in a supervised manner. We test our framework in both synthetic and real image data. The experimental results show the superiority of the proposed method over some other state-of-the-art deep brain network models.
| S-EPMC8293685 | biostudies-literature