scholarly journals Overcoming sparseness of biomedical networks to identify drug repositioning candidates

2020 ◽  
Author(s):  
Aleksandar Poleksic
Keyword(s):  
Biological Networks ◽  
Drug Targets ◽  
Drug Repositioning ◽  
Drug Repurposing ◽  
Drug Efficacy ◽  
Computational Procedure ◽  
Computational Method ◽  
Biomedical Data ◽  
Disease Associations ◽  
Disease Associated Genes

AbstractModeling complex biological systems is necessary to understand biochemical interactions behind pharmacological effects of drugs. Successful in silico drug repurposing requires a thorough exploration of diverse biochemical concepts and their relationships, including drug’s adverse reactions, drug targets, disease symptoms, as well as disease associated genes and their pathways, to name a few. We present a computational method for inferring drug-disease associations from complex but incomplete and biased biological networks. Our method employs the compressed sensing technique to overcome the sparseness of biomedical data and, in turn, to enrich the set of verified relationships between different biomedical entities. We present a strategy for identifying network paths supportive of drug efficacy as well as a computational procedure capable of combining different network patterns to better distinguish treatments from non-treatments. The data and programs are freely available at http://bioinfo.cs.uni.edu/AEONET.html.

scholarly journals Drug Repurposing Using Biological Networks

Processes ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 1057
Author(s):  
Francisco Javier Somolinos ◽  
Carlos León ◽  
Sara Guerrero-Aspizua
Keyword(s):  
Computational Methods ◽  
Biological Networks ◽  
High Performance ◽  
Biological Network ◽  
Drug Repositioning ◽  
Drug Repurposing ◽  
Network Models ◽  
Biomedical Data ◽  
Multiple Targets ◽  
Medical Indication

Drug repositioning is a strategy to identify new uses for existing, approved, or research drugs that are outside the scope of its original medical indication. Drug repurposing is based on the fact that one drug can act on multiple targets or that two diseases can have molecular similarities, among others. Currently, thanks to the rapid advancement of high-performance technologies, a massive amount of biological and biomedical data is being generated. This allows the use of computational methods and models based on biological networks to develop new possibilities for drug repurposing. Therefore, here, we provide an in-depth review of the main applications of drug repositioning that have been carried out using biological network models. The goal of this review is to show the usefulness of these computational methods to predict associations and to find candidate drugs for repositioning in new indications of certain diseases.

scholarly journals A Computational Approach for Pathway-Based Systemic Drug Influence

Processes ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 1063
Author(s):  
Shinuk Kim
Keyword(s):  
Gene Networks ◽  
Drug Targets ◽  
Drug Repositioning ◽  
Drug Efficacy ◽  
Rapid Expansion ◽  
Gene Sets ◽  
Development Risks ◽  
Drug Influence ◽  
Potential Drug Targets ◽  
Systemic Drug

Drug repositioning is a well-known method used to reduce the time, cost, and development risks involved in bringing a new drug to the market. The rapid expansion of high-throughput datasets has enabled computational research that can suggest new potential uses for existing drugs. Some computational methods allow the prediction of potential drug targets of a given disease from a systematic network. Despite numerous efforts, the path of many drugs’ efficacy in the human body remains unclear. Therefore, the present study attempted to understand drug efficacy by systematically focusing on functional gene sets. The purpose of this study was to carry out modeling to identify systemic gene networks (called drug paths) in drug-specific pathways. In our results, we found five different paths for five different drugs.

scholarly journals Genomics-driven drug discovery based on disease-susceptibility genes

2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Kyuto Sonehara ◽  
Yukinori Okada
Keyword(s):  
Drug Discovery ◽  
Drug Targets ◽  
Disease Susceptibility ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Drug Repurposing ◽  
Susceptibility Genes ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Disease Associations

AbstractGenome-wide association studies have identified numerous disease-susceptibility genes. As knowledge of gene–disease associations accumulates, it is becoming increasingly important to translate this knowledge into clinical practice. This challenge involves finding effective drug targets and estimating their potential side effects, which often results in failure of promising clinical trials. Here, we review recent advances and future perspectives in genetics-led drug discovery, with a focus on drug repurposing, Mendelian randomization, and the use of multifaceted omics data.

Computational drug repositioning based on multi-similarities bilinear matrix factorization

2020 ◽  
Author(s):  
Mengyun Yang ◽  
Gaoyan Wu ◽  
Qichang Zhao ◽  
Yaohang Li ◽  
Jianxin Wang
Keyword(s):  
Matrix Factorization ◽  
Drug Repositioning ◽  
Disease Association ◽  
Biological Entity ◽  
Biomedical Data ◽  
Supplementary Data ◽  
Practical Applications ◽  
Disease Associations ◽  
Association Matrix ◽  
Similarity Matrices

Abstract With the development of high-throughput technology and the accumulation of biomedical data, the prior information of biological entity can be calculated from different aspects. Specifically, drug–drug similarities can be measured from target profiles, drug–drug interaction and side effects. Similarly, different methods and data sources to calculate disease ontology can result in multiple measures of pairwise disease similarities. Therefore, in computational drug repositioning, developing a dynamic method to optimize the fusion process of multiple similarities is a crucial and challenging task. In this study, we propose a multi-similarities bilinear matrix factorization (MSBMF) method to predict promising drug-associated indications for existing and novel drugs. Instead of fusing multiple similarities into a single similarity matrix, we concatenate these similarity matrices of drug and disease, respectively. Applying matrix factorization methods, we decompose the drug–disease association matrix into a drug-feature matrix and a disease-feature matrix. At the same time, using these feature matrices as basis, we extract effective latent features representing the drug and disease similarity matrices to infer missing drug–disease associations. Moreover, these two factored matrices are constrained by non-negative factorization to ensure that the completed drug–disease association matrix is biologically interpretable. In addition, we numerically solve the MSBMF model by an efficient alternating direction method of multipliers algorithm. The computational experiment results show that MSBMF obtains higher prediction accuracy than the state-of-the-art drug repositioning methods in cross-validation experiments. Case studies also demonstrate the effectiveness of our proposed method in practical applications. Availability: The data and code of MSBMF are freely available at https://github.com/BioinformaticsCSU/MSBMF. Corresponding author: Jianxin Wang, School of Computer Science and Engineering, Central South University, Changsha, Hunan 410083, P. R. China. E-mail: [email protected] Supplementary Data: Supplementary data are available online at https://academic.oup.com/bib.

scholarly journals NEDD: a network embedding based method for predicting drug-disease associations

2020 ◽  
Vol 21 (S13) ◽  
Author(s):  
Renyi Zhou ◽  
Zhangli Lu ◽  
Huimin Luo ◽  
Ju Xiang ◽  
Min Zeng ◽  
...  
Keyword(s):  
Drug Repositioning ◽  
Computational Method ◽  
Heterogeneous Information ◽  
Gold Standard Dataset ◽  
Disease Similarity ◽  
Disease Associations ◽  
Meta Path ◽  
Approved Drugs ◽  
Low Dimensional ◽  
Novel Associations

Abstract Background Drug discovery is known for the large amount of money and time it consumes and the high risk it takes. Drug repositioning has, therefore, become a popular approach to save time and cost by finding novel indications for approved drugs. In order to distinguish these novel indications accurately in a great many of latent associations between drugs and diseases, it is necessary to exploit abundant heterogeneous information about drugs and diseases. Results In this article, we propose a meta-path-based computational method called NEDD to predict novel associations between drugs and diseases using heterogeneous information. First, we construct a heterogeneous network as an undirected graph by integrating drug-drug similarity, disease-disease similarity, and known drug-disease associations. NEDD uses meta paths of different lengths to explicitly capture the indirect relationships, or high order proximity, within drugs and diseases, by which the low dimensional representation vectors of drugs and diseases are obtained. NEDD then uses a random forest classifier to predict novel associations between drugs and diseases. Conclusions The experiments on a gold standard dataset which contains 1933 validated drug–disease associations show that NEDD produces superior prediction results compared with the state-of-the-art approaches.

scholarly journals Computational guided approach for drug repurposing against SARS-CoV-2

2021 ◽  
Author(s):  
Jigisha Anand ◽  
Tanmay Ghildiyal ◽  
Aakanksha Madhwal ◽  
Rishabh Bhatt ◽  
Devvret Verma ◽  
...  
Keyword(s):  
Drug Targets ◽  
De Novo ◽  
Drug Repositioning ◽  
Drug Repurposing ◽  
Computational Docking ◽  
Drug Candidates ◽  
Docking Tool ◽  
Inhibitory Potential ◽  
Approved Drugs ◽  
Tract Infections

Background: In the current SARS-CoV-2 outbreak, drug repositioning emerges as a promising approach to develop efficient therapeutics in comparison to de novo drug development. The present investigation screened 130 US FDA-approved drugs including hypertension, cardiovascular diseases, respiratory tract infections (RTI), antibiotics and antiviral drugs for their inhibitory potential against SARS-CoV-2. Materials & methods: The molecular drug targets against SARS-CoV-2 proteins were determined by the iGEMDOCK computational docking tool. The protein homology models were generated through SWISS Model workspace. The pharmacokinetics of all the ligands was determined by ADMET analysis. Results: The study identified 15 potent drugs exhibiting significant inhibitory potential against SARS-CoV-2. Conclusion: Our investigation has identified possible repurposed drug candidates to improve the current modus operandi of the treatment given to COVID-19 patients.

scholarly journals SAveRUNNER: A network-based algorithm for drug repurposing and its application to COVID-19

2021 ◽  
Vol 17 (2) ◽  
pp. e1008686
Author(s):  
Giulia Fiscon ◽  
Federica Conte ◽  
Lorenzo Farina ◽  
Paola Paci
Keyword(s):  
Drug Targets ◽  
De Novo ◽  
Drug Repositioning ◽  
Drug Repurposing ◽  
Gene Set Enrichment Analysis ◽  
Thrombin Inhibitors ◽  
New Combination ◽  
Human Coronavirus ◽  
Human Interactome ◽  
Off Label

The novelty of new human coronavirus COVID-19/SARS-CoV-2 and the lack of effective drugs and vaccines gave rise to a wide variety of strategies employed to fight this worldwide pandemic. Many of these strategies rely on the repositioning of existing drugs that could shorten the time and reduce the cost compared to de novo drug discovery. In this study, we presented a new network-based algorithm for drug repositioning, called SAveRUNNER (Searching off-lAbel dRUg aNd NEtwoRk), which predicts drug–disease associations by quantifying the interplay between the drug targets and the disease-specific proteins in the human interactome via a novel network-based similarity measure that prioritizes associations between drugs and diseases locating in the same network neighborhoods. Specifically, we applied SAveRUNNER on a panel of 14 selected diseases with a consolidated knowledge about their disease-causing genes and that have been found to be related to COVID-19 for genetic similarity (i.e., SARS), comorbidity (e.g., cardiovascular diseases), or for their association to drugs tentatively repurposed to treat COVID-19 (e.g., malaria, HIV, rheumatoid arthritis). Focusing specifically on SARS subnetwork, we identified 282 repurposable drugs, including some the most rumored off-label drugs for COVID-19 treatments (e.g., chloroquine, hydroxychloroquine, tocilizumab, heparin), as well as a new combination therapy of 5 drugs (hydroxychloroquine, chloroquine, lopinavir, ritonavir, remdesivir), actually used in clinical practice. Furthermore, to maximize the efficiency of putative downstream validation experiments, we prioritized 24 potential anti-SARS-CoV repurposable drugs based on their network-based similarity values. These top-ranked drugs include ACE-inhibitors, monoclonal antibodies (e.g., anti-IFNγ, anti-TNFα, anti-IL12, anti-IL1β, anti-IL6), and thrombin inhibitors. Finally, our findings were in-silico validated by performing a gene set enrichment analysis, which confirmed that most of the network-predicted repurposable drugs may have a potential treatment effect against human coronavirus infections.

scholarly journals MGRL: Predicting Drug-Disease Associations Based on Multi-Graph Representation Learning

2021 ◽  
Vol 12 ◽  
Author(s):  
Bo-Wei Zhao ◽  
Zhu-Hong You ◽  
Leon Wong ◽  
Ping Zhang ◽  
Hao-Yuan Li ◽  
...  
Keyword(s):  
High Efficiency ◽  
Drug Repositioning ◽  
Representation Learning ◽  
Computational Method ◽  
Graph Representation ◽  
Practical Applications ◽  
Study Results ◽  
Disease Associations ◽  
Better Than

Drug repositioning is an application-based solution based on mining existing drugs to find new targets, quickly discovering new drug-disease associations, and reducing the risk of drug discovery in traditional medicine and biology. Therefore, it is of great significance to design a computational model with high efficiency and accuracy. In this paper, we propose a novel computational method MGRL to predict drug-disease associations based on multi-graph representation learning. More specifically, MGRL first uses the graph convolution network to learn the graph representation of drugs and diseases from their self-attributes. Then, the graph embedding algorithm is used to represent the relationships between drugs and diseases. Finally, the two kinds of graph representation learning features were put into the random forest classifier for training. To the best of our knowledge, this is the first work to construct a multi-graph to extract the characteristics of drugs and diseases to predict drug-disease associations. The experiments show that the MGRL can achieve a higher AUC of 0.8506 based on five-fold cross-validation, which is significantly better than other existing methods. Case study results show the reliability of the proposed method, which is of great significance for practical applications.

Drug Repurposing Approaches: Existing Leads For Novel Threats And Drug Targets

2020 ◽  
Vol 21 ◽  
Author(s):  
Talambedu Usha ◽  
Sushil K. Middha ◽  
Anusha A. Kukanur ◽  
Rachamadugu V. Shravani ◽  
Mahantesh N. Anupama ◽  
...  
Keyword(s):  
Drug Targets ◽  
Drug Repositioning ◽  
Drug Repurposing ◽  
Risk Process ◽  
Clinical Analysis ◽  
Literature Mining ◽  
Semantic Inference ◽  
Inference Network ◽  
Academic Publications ◽  
Old Drugs

: Drug Repurposing (DR) is an alternative to the traditional drug discovery process. It is cost and time effective, with high returns and low risk process that can tackle the increasing need for interventions for varied diseases and new outbreaks. Repurposing of old drugs for other diseases has gained a wider attention, as there have been several old drugs approved by FDA for new diseases. In the global emergency of COVID19 pandemic, this is one of the strategies implemented in repurposing of old anti-infective, anti-rheumatic and anti-thrombotic drugs. The goal of the current review is to elaborate the process of DR, its advantages, repurposed drugs for a plethora of disorders, and the evolution of related academic publications. Further, detailed are the computational approaches: literature mining and semantic inference, network-based drug repositioning, signature matching, retrospective clinical analysis, molecular docking and experimental phenotypic screening. We discuss the legal and economical potential barriers in DR, existent collaborative models and recommendations for overcoming these hurdles and leveraging the complete potential of DR in finding new indications.

scholarly journals Drug repurposing for COVID-19 based on an integrative meta-analysis of SARS-CoV-2 induced gene signature in human airway epithelium

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257784
Author(s):  
Rajaneesh K. Gupta ◽  
Enyinna L. Nwachuku ◽  
Benjamin E. Zusman ◽  
Ruchira M. Jha ◽  
Ava M. Puccio
Keyword(s):  
Gene Networks ◽  
Drug Targets ◽  
Drug Repositioning ◽  
Meta Analysis ◽  
Drug Repurposing ◽  
Gene Signature ◽  
Airway Epithelial Cells ◽  
Gene Ranking ◽  
Human Airway ◽  
Ranking Algorithms

Drug repurposing has the potential to bring existing de-risked drugs for effective intervention in an ongoing pandemic—COVID-19 that has infected over 131 million, with 2.8 million people succumbing to the illness globally (as of April 04, 2021). We have used a novel `gene signature’-based drug repositioning strategy by applying widely accepted gene ranking algorithms to prioritize the FDA approved or under trial drugs. We mined publically available RNA sequencing (RNA-Seq) data using CLC Genomics Workbench 20 (QIAGEN) and identified 283 differentially expressed genes (FDR<0.05, log2FC>1) after a meta-analysis of three independent studies which were based on severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection in primary human airway epithelial cells. Ingenuity Pathway Analysis (IPA) revealed that SARS-CoV-2 activated key canonical pathways and gene networks that intricately regulate general anti-viral as well as specific inflammatory pathways. Drug database, extracted from the Metacore and IPA, identified 15 drug targets (with information on COVID-19 pathogenesis) with 46 existing drugs as potential-novel candidates for repurposing for COVID-19 treatment. We found 35 novel drugs that inhibit targets (ALPL, CXCL8, and IL6) already in clinical trials for COVID-19. Also, we found 6 existing drugs against 4 potential anti-COVID-19 targets (CCL20, CSF3, CXCL1, CXCL10) that might have novel anti-COVID-19 indications. Finally, these drug targets were computationally prioritized based on gene ranking algorithms, which revealed CXCL10 as the common and strongest candidate with 2 existing drugs. Furthermore, the list of 283 SARS-CoV-2-associated proteins could be valuable not only as anti-COVID-19 targets but also useful for COVID-19 biomarker development.

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