scholarly journals Integration of the Drug–Gene Interaction Database (DGIdb 4.0) with open crowdsource efforts

2020 ◽  
Vol 49 (D1) ◽  
pp. D1144-D1151
Author(s):  
Sharon L Freshour ◽  
Susanna Kiwala ◽  
Kelsy C Cotto ◽  
Adam C Coffman ◽  
Joshua F McMichael ◽  
...  
Keyword(s):  
Interaction Network ◽  
Gene Interaction ◽  
Application Programming Interface ◽  
Application Framework ◽  
Interaction Data ◽  
Gene Interaction Network ◽  
Web Based ◽  
Web Resource ◽  
Interaction Database ◽  
Primary Focus

Abstract The Drug-Gene Interaction Database (DGIdb, www.dgidb.org) is a web resource that provides information on drug-gene interactions and druggable genes from publications, databases, and other web-based sources. Drug, gene, and interaction data are normalized and merged into conceptual groups. The information contained in this resource is available to users through a straightforward search interface, an application programming interface (API), and TSV data downloads. DGIdb 4.0 is the latest major version release of this database. A primary focus of this update was integration with crowdsourced efforts, leveraging the Drug Target Commons for community-contributed interaction data, Wikidata to facilitate term normalization, and export to NDEx for drug-gene interaction network representations. Seven new sources have been added since the last major version release, bringing the total number of sources included to 41. Of the previously aggregated sources, 15 have been updated. DGIdb 4.0 also includes improvements to the process of drug normalization and grouping of imported sources. Other notable updates include the introduction of a more sophisticated Query Score for interaction search results, an updated Interaction Score, the inclusion of interaction directionality, and several additional improvements to search features, data releases, licensing documentation and the application framework.

scholarly journals Integration of the Drug-Gene Interaction Database (DGIdb) with open crowdsource efforts

2020 ◽  
Author(s):  
Sharon Freshour ◽  
Susanna Kiwala ◽  
Kelsy C. Cotto ◽  
Adam C. Coffman ◽  
Joshua F. McMichael ◽  
...  
Keyword(s):  
Routine Data ◽  
Gene Interaction ◽  
Application Programming Interface ◽  
Web Based ◽  
Web Resource ◽  
Interaction Database ◽  
Manual Curation ◽  
Application Programming ◽  
Further Development ◽  
Programming Interface

ABSTRACTThe Drug-Gene Interaction Database (DGIdb, www.dgidb.org) is a web resource that provides information on drug-gene interactions and druggable genes from various sources including publications, databases, and other web-based sources in one resource. These drug, gene, and interaction claims are normalized and grouped to identify aliases, merge concepts, and reduce redundancy. The information contained in this resource is available to users through a straightforward search interface, an application programming interface (API), and TSV data downloads. DGIdb 4.0 is the latest major update of this database. Seven new sources have been added, bringing the total number of sources included to 41. Of the previously aggregated sources, 15 have been updated. DGIdb 4.0 also includes improvements to the process of drug normalization and grouping of imported sources. Other notable updates include further development of automatic jobs for routine data updates, more sophisticated query scores for interaction search results, extensive manual curation of interaction source link outs, and the inclusion of interaction directionality. A major focus of this update was integration with crowd-sourced efforts, including leveraging the curation activities of Drug Target Commons, using Wikidata to facilitate term normalization, and integrating into NDEx for producing network representations.

scholarly journals Drug Repurposing Using Modularity Clustering in Drug-Drug Similarity Networks Based on Drug–Gene Interactions

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2117
Author(s):  
Vlad Groza ◽  
Mihai Udrescu ◽  
Alexandru Bozdog ◽  
Lucreţia Udrescu
Keyword(s):  
Interaction Network ◽  
Drug Repurposing ◽  
Gene Interaction ◽  
New Drugs ◽  
Interaction Data ◽  
Gene Interaction Network ◽  
Drug Databases ◽  
Drug Similarity

Drug repurposing is a valuable alternative to traditional drug design based on the assumption that medicines have multiple functions. Computer-based techniques use ever-growing drug databases to uncover new drug repurposing hints, which require further validation with in vitro and in vivo experiments. Indeed, such a scientific undertaking can be particularly effective in the case of rare diseases (resources for developing new drugs are scarce) and new diseases such as COVID-19 (designing new drugs require too much time). This paper introduces a new, completely automated computational drug repurposing pipeline based on drug–gene interaction data. We obtained drug–gene interaction data from an earlier version of DrugBank, built a drug–gene interaction network, and projected it as a drug–drug similarity network (DDSN). We then clustered DDSN by optimizing modularity resolution, used the ATC codes distribution within each cluster to identify potential drug repurposing candidates, and verified repurposing hints with the latest DrugBank ATC codes. Finally, using the best modularity resolution found with our method, we applied our pipeline to the latest DrugBank drug–gene interaction data to generate a comprehensive drug repurposing hint list.

scholarly journals DGIdb 3.0: a redesign and expansion of the drug-gene interaction database

2017 ◽  
Author(s):  
Kelsy C. Cotto ◽  
Alex H. Wagner ◽  
Yang-Yang Feng ◽  
Susanna Kiwala ◽  
Adam C. Coffman ◽  
...  
Keyword(s):  
User Interface ◽  
Web Application ◽  
Response Times ◽  
Gene Interaction ◽  
Application Programming Interface ◽  
Gene Interactions ◽  
Application Framework ◽  
Interaction Database ◽  
Search Filters ◽  
Ease Of Access

ABSTRACTThe Drug-Gene Interaction Database (DGIdb, www.dgidb.org) consolidates, organizes, and presents drug-gene interactions and gene druggability information from papers, databases, and web resources. DGIdb normalizes content from more than thirty disparate sources and allows for user-friendly advanced browsing, searching and filtering for ease of access through an intuitive web user interface, application programming interface (API), and public cloud-based server image. DGIdb v3.0 represents a major update of the database. Nine of the previously included twenty-eight sources were updated. Six new resources were added, bringing the total number of sources to thirty-three. These updates and additions of sources have cumulatively resulted in 56,309 interaction claims. This has also substantially expanded the comprehensive catalogue of druggable genes and antineoplastic drug-gene interactions included in the DGIdb. Along with these content updates, v3.0 has received a major overhaul of its codebase, including an updated user interface, preset interaction search filters, consolidation of interaction information into interaction groups, greatly improved search response times, and upgrading the underlying web application framework. In addition, the expanded API features new endpoints which allow users to extract more detailed information about queried drugs, genes, and drug-gene interactions, including listings of PubMed IDs (PMIDs), interaction type, and other interaction metadata.

scholarly journals Community Detection in Large-Scale Bipartite Biological Networks

2021 ◽  
Vol 12 ◽  
Author(s):  
Genís Calderer ◽  
Marieke L. Kuijjer
Keyword(s):  
Biological Networks ◽  
Large Scale ◽  
Interaction Network ◽  
Gene Interaction ◽  
Community Structures ◽  
Gene Interaction Network ◽  
Structure Detection ◽  
Wide Range ◽  
Disease Associations ◽  
Or Gene

Networks are useful tools to represent and analyze interactions on a large, or genome-wide scale and have therefore been widely used in biology. Many biological networks—such as those that represent regulatory interactions, drug-gene, or gene-disease associations—are of a bipartite nature, meaning they consist of two different types of nodes, with connections only forming between the different node sets. Analysis of such networks requires methodologies that are specifically designed to handle their bipartite nature. Community structure detection is a method used to identify clusters of nodes in a network. This approach is especially helpful in large-scale biological network analysis, as it can find structure in networks that often resemble a “hairball” of interactions in visualizations. Often, the communities identified in biological networks are enriched for specific biological processes and thus allow one to assign drugs, regulatory molecules, or diseases to such processes. In addition, comparison of community structures between different biological conditions can help to identify how network rewiring may lead to tissue development or disease, for example. In this mini review, we give a theoretical basis of different methods that can be applied to detect communities in bipartite biological networks. We introduce and discuss different scores that can be used to assess the quality of these community structures. We then apply a wide range of methods to a drug-gene interaction network to highlight the strengths and weaknesses of these methods in their application to large-scale, bipartite biological networks.

scholarly journals Bioinformatic Analysis of Neuroimmune Mechanism of Neuropathic Pain

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Hao Yu ◽  
Yang Liu ◽  
Chao Li ◽  
Jianhao Wang ◽  
Bo Yu ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Inflammatory Responses ◽  
Interaction Network ◽  
Gene Interaction ◽  
Bioinformatic Analysis ◽  
Venn Diagram ◽  
Hub Genes ◽  
Gene Interaction Network ◽  
Pathway Enrichment ◽  
Protein Protein Interaction

Background. Neuropathic pain (NP) is a devastating complication following nerve injury, and it can be alleviated by regulating neuroimmune direction. We aimed to explore the neuroimmune mechanism and identify some new diagnostic or therapeutic targets for NP treatment via bioinformatic analysis. Methods. The microarray GSE18803 was downloaded and analyzed using R. The Venn diagram was drawn to find neuroimmune-related differentially expressed genes (DEGs) in neuropathic pain. Gene Ontology (GO), pathway enrichment, and protein-protein interaction (PPI) network were used to analyze DEGs, respectively. Besides, the identified hub genes were submitted to the DGIdb database to find relevant therapeutic drugs. Results. A total of 91 neuroimmune-related DEGs were identified. The results of GO and pathway enrichment analyses were closely related to immune and inflammatory responses. PPI analysis showed two important modules and 8 hub genes: PTPRC, CD68, CTSS, RAC2, LAPTM5, FCGR3A, CD53, and HCK. The drug-hub gene interaction network was constructed by Cytoscape, and it included 24 candidate drugs and 3 hub genes. Conclusion. The present study helps us better understand the neuroimmune mechanism of neuropathic pain and provides some novel insights on NP treatment, such as modulation of microglia polarization and targeting bone resorption. Besides, CD68, CTSS, LAPTM5, FCGR3A, and CD53 may be used as early diagnostic biomarkers and the gene HCK can be a therapeutic target.

scholarly journals A yeast phenomic model for the gene interaction network modulating CFTR-ΔF508 protein biogenesis

10.1186/gm404 ◽  
2012 ◽  
Vol 4 (12) ◽  
Author(s):  
Raymond J Louie ◽  
Jingyu Guo ◽  
John W Rodgers ◽  
Rick White ◽  
Najaf A Shah ◽  
...  
Keyword(s):  
Interaction Network ◽  
Gene Interaction ◽  
Gene Interaction Network ◽  
Protein Biogenesis

Rheumatoid arthritis–associated DNA methylation sites in peripheral blood mononuclear cells

2018 ◽  
Vol 78 (1) ◽  
pp. 36-42 ◽  
Author(s):  
Hong Zhu ◽  
Long-Fei Wu ◽  
Xing-Bo Mo ◽  
Xin Lu ◽  
Hui Tang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Mrna Expression ◽  
Mononuclear Cells ◽  
Interaction Network ◽  
Gene Interaction ◽  
Jurkat Cells ◽  
Gene Interaction Network ◽  
Peripheral Blood Mononuclear ◽  
Inference Tests ◽  
Inducible Gene

ObjectivesTo identify novel DNA methylation sites significant for rheumatoid arthritis (RA) and comprehensively understand their underlying pathological mechanism.MethodsWe performed (1) genome-wide DNA methylation and mRNA expression profiling in peripheral blood mononuclear cells from RA patients and health controls; (2) correlation analysis and causal inference tests for DNA methylation and mRNA expression data; (3) differential methylation genes regulatory network construction; (4) validation tests of 10 differential methylation positions (DMPs) of interest and corresponding gene expressions; (5) correlation between PARP9 methylation and its mRNA expression level in Jurkat cells and T cells from patients with RA; (6) testing the pathological functions of PARP9 in Jurkat cells.ResultsA total of 1046 DNA methylation positions were associated with RA. The identified DMPs have regulatory effects on mRNA expressions. Causal inference tests identified six DNA methylation–mRNA–RA regulatory chains (eg, cg00959259-PARP9-RA). The identified DMPs and genes formed an interferon-inducible gene interaction network (eg, MX1, IFI44L, DTX3L and PARP9). Key DMPs and corresponding genes were validated their differences in additional samples. Methylation of PARP9 was correlated with mRNA level in Jurkat cells and T lymphocytes isolated from patients with RA. The PARP9 gene exerted significant effects on Jurkat cells (eg, cell cycle, cell proliferation, cell activation and expression of inflammatory factor IL-2).ConclusionsThis multistage study identified an interferon-inducible gene interaction network associated with RA and highlighted the importance of PARP9 gene in RA pathogenesis. The results enhanced our understanding of the important role of DNA methylation in pathology of RA.

scholarly journals Genomic variant annotation workflow for clinical applications

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 1963 ◽  
Author(s):  
Thomas Thurnherr ◽  
Franziska Singer ◽  
Daniel J. Stekhoven ◽  
Niko Beerenwinkel
Keyword(s):  
Gene Interaction ◽  
Clinical Applications ◽  
Interaction Data ◽  
Bioconductor Package ◽  
Variant Annotation ◽  
Interaction Database ◽  
Genomic Aberrations ◽  
Genomic Variant ◽  
Different Levels ◽  
Generation Sequencing

Annotation and interpretation of DNA aberrations identified through next-generation sequencing is becoming an increasingly important task. Even more so in the context of data analysis pipelines for medical applications, where genomic aberrations are associated with phenotypic and clinical features. Here we describe a workflow to identify potential gene targets in aberrated genes or pathways and their corresponding drugs. To this end, we provide the R/Bioconductor package rDGIdb, an R wrapper to query the drug-gene interaction database (DGIdb). DGIdb accumulates drug-gene interaction data from 15 different resources and allows filtering on different levels. The rDGIdb package makes these resources and tools available to R users. Moreover, rDGIdb queries can be automated through incorporation of the rDGIdb package into NGS sequencing pipelines.

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