Browse
Submit Data
Databases
API
Help

Dataset Information

16 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A two-step drug repositioning method based on a protein-protein interaction network of genes shared by two diseases and the similarity of drugs.

ABSTRACT: The present study proposed a two-step drug repositioning method based on a protein-protein interaction (PPI) network of two diseases and the similarity of the drugs prescribed for one of the two. In the proposed method, first, lists of disease related genes were obtained from a meta-database called Genotator. Then genes shared by a pair of diseases were sought. At the first step of the method, if a drug having its target(s) in the PPI network, the drug was deemed a repositioning candidate. Because targets of many drugs are still unknown, the similarities between the prescribed drugs for a specific disease were used to infer repositioning candidates at the second step. As a first attempt, we applied the proposed method to four different types of diseases: hypertension, diabetes mellitus, Crohn disease, and autism. Some repositioning candidates were found both at the first and second steps.

SUBMITTER: Fukuoka Y

PROVIDER: S-EPMC3563404 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

A two-step drug repositioning method based on a protein-protein interaction network of genes shared by two diseases and the similarity of drugs.

Fukuoka Yutaka Y Takei Daiki D Ogawa Hisamichi H

Bioinformation 20130118 2

The present study proposed a two-step drug repositioning method based on a protein-protein interaction (PPI) network of two diseases and the similarity of the drugs prescribed for one of the two. In the proposed method, first, lists of disease related genes were obtained from a meta-database called Genotator. Then genes shared by a pair of diseases were sought. At the first step of the method, if a drug having its target(s) in the PPI network, the drug was deemed a repositioning candidate. Becau ...[more]

PMID: 23390352

Similar Datasets

Discovery of protein interaction networks shared by diseases.

Project description:The study of protein-protein interactions is essential to define the molecular networks that contribute to maintain homeostasis of an organism's body functions. Disruptions in protein interaction networks have been shown to result in diseases in both humans and animals. Monogenic diseases disrupting biochemical pathways such as hereditary coagulopathies (e.g. hemophilia), provided a deep insight in the biochemical pathways of acquired coagulopathies of complex diseases. Indeed, a variety of complex liver diseases can lead to decreased synthesis of the same set of coagulation factors as in hemophilia. Similarly, more complex diseases such as different cancers have been shown to result from malfunctions of common proteins pathways. In order to discover, in high throughput, the molecular underpinnings of poorly characterized diseases, we present a statistical method to identify shared protein interaction network(s) between diseases. Integrating (i) a protein interaction network with (ii) disease to protein relationships derived from mining Gene Ontology annotations and the biomedical literature with natural language understanding (PhenoGO), we identified protein-protein interactions that were associated with pairs of diseases and calculated the statistical significance of the occurrence of interactions in the protein interaction knowledgebase. Significant correlations between diseases and shared protein networks were identified and evaluated in this study, demonstrating the high precision of the approach and correct non-trivial predictions, signifying the potential for discovery. In conclusion, we demonstrate that the associations between diseases are directly correlated to their underlying protein-protein interaction networks, possibly providing insight into the underlying molecular mechanisms of phenotypes and biological processes disrupted in related diseases.

| S-EPMC2886192 | biostudies-other

A New Method for Computational Drug Repositioning Using Drug Pairwise Similarity.

Project description:The traditional de novo drug discovery is known as a high cost and high risk process. In response, recently there is an increasing interest in discovering new indications for known drugs-a process known as drug repositioning-using computational methods. In this study, we present a new systematic approach for identifying potential new indications of an existing drug through its relation to similar drugs. Different from the previous similarity-based methods, we adapted a novel bipartite-graph based method when considering common drug targets and their interaction information. Furthermore, we added drug structure information into the calculation of drug pairwise similarity. In cross-validation experiments, our method achieved a sensitivity of 0.77 and specificity of 0.92 (AUC = 0.888) and compared favorably to the state of the art. When compared with a control group of drug uses, our drug repositioning results were found to be significantly enriched in both the biomedical literature and clinical trials. Our results indicate that combining chemical structure and drug target information results in better prediction performance and that the proposed approach successfully captures the implicit information between drug targets.

| S-EPMC4175719 | biostudies-literature

A computational drug repositioning method applied to rare diseases: Adrenocortical carcinoma.

Project description:Rare or orphan diseases affect only small populations, thereby limiting the economic incentive for the drug development process, often resulting in a lack of progress towards treatment. Drug repositioning is a promising approach in these cases, due to its low cost. In this approach, one attempts to identify new purposes for existing drugs that have already been developed and approved for use. By applying the process of drug repositioning to identify novel treatments for rare diseases, we can overcome the lack of economic incentives and make concrete progress towards new therapies. Adrenocortical Carcinoma (ACC) is a rare disease with no practical and definitive therapeutic approach. We apply Heter-LP, a new method of drug repositioning, to suggest novel therapeutic avenues for ACC. Our analysis identifies innovative putative drug-disease, drug-target, and disease-target relationships for ACC, which include Cosyntropin (drug) and DHCR7, IGF1R, MC1R, MAP3K3, TOP2A (protein targets). When results are analyzed using all available information, a number of novel predicted associations related to ACC appear to be valid according to current knowledge. We expect the predicted relations will be useful for drug repositioning in ACC since the resulting ranked lists of drugs and protein targets can be used to expedite the necessary clinical processes.

| S-EPMC7264316 | biostudies-literature

Predicting associations among drugs, targets and diseases by tensor decomposition for drug repositioning.

Project description:BACKGROUND:Development of new drugs is a time-consuming and costly process, and the cost is still increasing in recent years. However, the number of drugs approved by FDA every year per dollar spent on development is declining. Drug repositioning, which aims to find new use of existing drugs, attracts attention of pharmaceutical researchers due to its high efficiency. A variety of computational methods for drug repositioning have been proposed based on machine learning approaches, network-based approaches, matrix decomposition approaches, etc. RESULTS: We propose a novel computational method for drug repositioning. We construct and decompose three-dimensional tensors, which consist of the associations among drugs, targets and diseases, to derive latent factors reflecting the functional patterns of the three kinds of entities. The proposed method outperforms several baseline methods in recovering missing associations. Most of the top predictions are validated by literature search and computational docking. Latent factors are used to cluster the drugs, targets and diseases into functional groups. Topological Data Analysis (TDA) is applied to investigate the properties of the clusters. We find that the latent factors are able to capture the functional patterns and underlying molecular mechanisms of drugs, targets and diseases. In addition, we focus on repurposing drugs for cancer and discover not only new therapeutic use but also adverse effects of the drugs. In the in-depth study of associations among the clusters of drugs, targets and cancer subtypes, we find there exist strong associations between particular clusters. CONCLUSIONS:The proposed method is able to recover missing associations, discover new predictions and uncover functional clusters of drugs, targets and diseases. The clustering of drugs, targets and diseases, as well as the associations among the clusters, provides a new guiding framework for drug repositioning.

| S-EPMC6912989 | biostudies-literature

Cheaper faster drug development validated by the repositioning of drugs against neglected tropical diseases.

Project description:There is an urgent need to make drug discovery cheaper and faster. This will enable the development of treatments for diseases currently neglected for economic reasons, such as tropical and orphan diseases, and generally increase the supply of new drugs. Here, we report the Robot Scientist 'Eve' designed to make drug discovery more economical. A Robot Scientist is a laboratory automation system that uses artificial intelligence (AI) techniques to discover scientific knowledge through cycles of experimentation. Eve integrates and automates library-screening, hit-confirmation, and lead generation through cycles of quantitative structure activity relationship learning and testing. Using econometric modelling we demonstrate that the use of AI to select compounds economically outperforms standard drug screening. For further efficiency Eve uses a standardized form of assay to compute Boolean functions of compound properties. These assays can be quickly and cheaply engineered using synthetic biology, enabling more targets to be assayed for a given budget. Eve has repositioned several drugs against specific targets in parasites that cause tropical diseases. One validated discovery is that the anti-cancer compound TNP-470 is a potent inhibitor of dihydrofolate reductase from the malaria-causing parasite Plasmodium vivax.

| S-EPMC4345494 | biostudies-literature

GREP: genome for REPositioning drugs.

Project description:SUMMARY:Making use of accumulated genetic knowledge for clinical practice is our next goal in human genetics. Here we introduce GREP (Genome for REPositioning drugs), a standalone python software to quantify an enrichment of the user-defined set of genes in the target of clinical indication categories and to capture potentially repositionable drugs targeting the gene set. We show that genes identified by the large-scale genome-wide association studies were robustly enriched in the approved drugs to treat the trait of interest. This enrichment analysis was also highly applicable to other sets of biological genes such as those identified by gene expression studies and genes somatically mutated in cancers. This software should accelerate investigators to reposition drugs to other indications with the guidance of known genomics. AVAILABILITY AND IMPLEMENTATION:GREP is available at https://github.com/saorisakaue/GREP as a python source code. SUPPLEMENTARY INFORMATION:Supplementary data are available at Bioinformatics online.

| S-EPMC6761931 | biostudies-literature

Repositioning Drugs on Human Influenza A Viruses Based on a Novel Nuclear Norm Minimization Method.

Project description:Influenza A viruses, especially H3N2 and H1N1 subtypes, are viruses that often spread among humans and cause influenza pandemic. There have been several big influenza pandemics that have caused millions of human deaths in history, and the threat of influenza viruses to public health is still serious nowadays due to the frequent antigenic drift and antigenic shift events. However, only few effective anti-flu drugs have been developed to date. The high development cost, long research and development time, and drug side effects are the major bottlenecks, which could be relieved by drug repositioning. In this study, we proposed a novel antiviral Drug Repositioning method based on minimizing Matrix Nuclear Norm (DRMNN). Specifically, a virus-drug correlation database consisting of 34 viruses and 205 antiviral drugs was first curated from public databases and published literature. Together with drug similarity on chemical structure and virus sequence similarity, we formulated the drug repositioning problem as a low-rank matrix completion problem, which was solved by minimizing the nuclear norm of a matrix with a few regularization terms. DRMNN was compared with three recent association prediction algorithms. The AUC of DRMNN in the global fivefold cross-validation (fivefold CV) is 0.8661, and the AUC in the local leave-one-out cross-validation (LOOCV) is 0.6929. Experiments have shown that DRMNN is better than other algorithms in predicting which drugs are effective against influenza A virus. With H3N2 as an example, 10 drugs most likely to be effective against H3N2 viruses were listed, among which six drugs were reported, in other literature, to have some effect on the viruses. The protein docking experiments between the chemical structure of the prioritized drugs and viral hemagglutinin protein also provided evidence for the potential of the predicted drugs for the treatment of influenza.

| S-EPMC7849835 | biostudies-literature

Human enterovirus 71 protein interaction network prompts antiviral drug repositioning.

Project description:As a predominant cause of human hand, foot, and mouth disease, enterovirus 71 (EV71) infection may lead to serious diseases and result in severe consequences that threaten public health and cause widespread panic. Although the systematic identification of physical interactions between viral proteins and host proteins provides initial information for the recognition of the cellular mechanism involved in viral infection and the development of new therapies, EV71-host protein interactions have not been explored. Here, we identified interactions between EV71 proteins and host cellular proteins and confirmed the functional relationships of EV71-interacting proteins (EIPs) with virus proliferation and infection by integrating a human protein interaction network and by functional annotation. We found that most EIPs had known interactions with other viruses. We also predicted ATP6V0C as a broad-spectrum essential host factor and validated its essentiality for EV71 infection in vitro. EIPs and their interacting proteins were more likely to be targets of anti-inflammatory and neurological drugs, indicating their potential to serve as host-oriented antiviral targets. Thus, we used a connectivity map to find drugs that inhibited EIP expression. We predicted tanespimycin as a candidate and demonstrated its antiviral efficiency in vitro. These findings provide the first systematic identification of EV71-host protein interactions, an analysis of EIP protein characteristics and a demonstration of their value in developing host-oriented antiviral therapies.

| S-EPMC5318855 | biostudies-other

Project description:Interactions between proteins play a key role in many cellular processes. Studying protein-protein interactions that share similar interaction interfaces may shed light on their evolution and could be helpful in elucidating the mechanisms behind stability and dynamics of the protein complexes. When two complexes share structurally similar subunits, the similarity of the interaction interfaces can be found through a structural superposition of the subunits. However, an accurate detection of similarity between the protein complexes containing subunits of unrelated structure remains an open problem. Here, we present an alignment-free machine learning approach to measure interface similarity. The approach relies on the feature-based representation of protein interfaces and does not depend on the superposition of the interacting subunit pairs. Specifically, we develop an SVM classifier of similar and dissimilar interfaces and derive a feature-based interface similarity measure. Next, the similarity measure is applied to a set of 2,806×2,806 binary complex pairs to build a hierarchical classification of protein-protein interactions. Finally, we explore case studies of similar interfaces from each level of the hierarchy, considering cases when the subunits forming interactions are either homologous or structurally unrelated. The analysis has suggested that the positions of charged residues in the homologous interfaces are not necessarily conserved and may exhibit more complex conservation patterns.

| S-EPMC3093400 | biostudies-literature

MeSHDD: Literature-based drug-drug similarity for drug repositioning.

Project description:ObjectiveDrug repositioning is a promising methodology for reducing the cost and duration of the drug discovery pipeline. We sought to develop a computational repositioning method leveraging annotations in the literature, such as Medical Subject Heading (MeSH) terms.MethodsWe developed software to determine significantly co-occurring drug-MeSH term pairs and a method to estimate pair-wise literature-derived distances between drugs.ResultsWe found that literature-based drug-drug similarities predicted the number of shared indications across drug-drug pairs. Clustering drugs based on their similarity revealed both known and novel drug indications. We demonstrate the utility of our approach by generating repositioning hypotheses for the commonly used diabetes drug metformin.ConclusionOur study demonstrates that literature-derived similarity is useful for identifying potential repositioning opportunities. We provided open-source code and deployed a free-to-use, interactive application to explore our database of similarity-based drug clusters (available at http://apps.chiragjpgroup.org/MeSHDD/ ).

| S-EPMC5391732 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data