Literature Evidence in Open Targets – a target validation platform

Kafkas, Şenay; Dunham, Ian; McEntyre, Johanna

doi:10.1101/124719

Cited by 4 publications

(2 citation statements)

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“…The Open Targets platform is a comprehensive and robust data integration platform for accessing and visualizing potential drug targets related to diseases. It brings together a variety of data types designed to help users identify and prioritize targets for further research (20). The disease name 'osteoarthritis' was entered into the search window in the Open Targets platform database and target proteins were collected for further analysis.…”

Section: Methodsmentioning

confidence: 99%

Anti‑inflammatory activity of Radix Angelicae biseratae in the treatment of osteoarthritis determined by systematic pharmacology and in vitro experiments

Chen

Zheng

et al. 2020

Exp Ther Med

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Radix Angelicae biseratae is a widely used Chinese traditional herbal medicine for osteoarthritis (OA). Its therapeutic efficacy has been confirmed in clinical practice. However, its mechanisms of action in treating OA have remained elusive. The purpose of the present study was to identify active components with good oral bioavailability and drug-like properties from Radix Angelicae biseratae through systematic pharmacology and in vitro experiments to determine targets of Radix Angelicae biseratae in the treatment of OA. The functional components of Radix Angelicae biseratae were screened from the Traditional Chinese Medicine Systems Pharmacology database based on oral bioavailability and drug-like properties. Subsequently, the databases STITCH, Open Targets Platform and DrugBank were searched and microarray analysis was performed to screen the active components of Radix Angelicae biseratae to treat OA and predict its potential target proteins. The interaction network and protein interaction network were then generated and examined, molecular docking between active components and targets was performed and the enrichment of potential target proteins was analyzed. Finally, reverse transcription-quantitative (RT-q)PCR and western blot analyses were used to verify the therapeutic effect of Radix Angelicae biseratae extract on the expression of OA-associated target proteins. The results provided eight active components in Radix Angelicae biseratae, which were firmly linked to 20 targets of OA. In combination with molecular docking and the analysis of the interaction network between components and targets, it was suggested that sitosterol was a major active component of Radix Angelicae biseratae in the treatment of OA. Protein interaction network analysis suggested that prostaglandin-endoperoxide synthase 2 (PTGS2), nitric oxide synthase 3 and cytochrome P450 2B6 may be critical targets for Radix Angelicae biseratae in the treatment of OA. In addition, RT-qPCR and western blot analyses suggested that Radix Angelicae biseratae extract inhibited the mRNA and protein expression of PTGS2 in degenerative articular cartilage cells in vitro, whilst other targets remain to be verified. Functional enrichment analysis indicated that Radix Angelicae biseratae confers pharmacological efficacy towards OA through exerting anti-inflammatory effects and immune regulation.

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Section: Methodsmentioning

confidence: 99%

Anti‑inflammatory activity of Radix Angelicae biseratae in the treatment of osteoarthritis determined by systematic pharmacology and in vitro experiments

Chen

Zheng

et al. 2020

Exp Ther Med

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“…ALS is an abbreviation both for "Amyotrophic Lateral Sclerosis" and "Advanced 49 Life Support"), we used a disease abbreviation filter for screening out the ambiguous 50 abbreviations that could be introduced during the annotation process [16]. Briefly, precision co-occurrence method.…”

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confidence: 99%

Ontology based mining of pathogen-disease associations from literature

Kafkas

Hoehndorf

2018

Preprint

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BackgroundInfectious diseases claim millions of lives especially in the developing countries each year, and resistance to drugs is an emerging threat worldwide. Identification of causative pathogens accurately and rapidly plays a key role in the success of treatment. To support infectious disease research and mechanisms of infection, there is a need for an open resource on pathogen-disease associations that can be utilized in computational studies. A large number of pathogen-disease associations is available from the literature in unstructured form and we need automated methods to extract the data. ResultsWe developed a text mining system designed for extracting pathogen-disease relations from literature. Our approach utilizes background knowledge from an ontology and statistical methods for extracting associations between pathogens and diseases. In total, we extracted a total of 3,420 pathogen-disease associations from literature. We integrated our literature-derived associations into a database which links pathogens to their phenotypes for supporting infectious disease research. ConclusionsTo the best of our knowledge, we present the first study focusing on extracting pathogen-disease associations from publications. We believe the text mined data can be utilized as a valuable resource for infectious disease research. All the data is publicly available from https://github.com/bio-ontology-research-group/padimi and through a public SPARQL endpoint from http://patho.phenomebrowser.net/.

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