scholarly journals Disease mechanism, drug-target and biomarker prediction software: Application on prostate cancer and validation

2017 ◽  
Author(s):  
Gokmen Altay ◽  
Elmar Nurmemmedov ◽  
Santosh Kesari ◽  
David E. Neal

AbstractWe present an R software package that performs at genome-wide level differential network analysis and infers only disease-specific molecular interactions between two different cell conditions. This helps revealing the disease mechanism and predicting most influential genes as potential drug targets or biomarkers of the disease condition of interest. As an exemplary analysis, we performed an application of the software over LNCaP datasets and, out of approximately 25000 genes, predicted CXCR7 and CXCR4 together as drug targets of LNCaP prostate cancer dataset. We further successfully validated them with our initial wet-lab experiments. The introduced software can be applied to all the diseases, especially cancer, with gene expression data of two different conditions (e.g. tumor vs normal) and thus has the potential of a global benefit. As a distinct remark, our software provide the causal disease mechanism with multiple potential drug-targets rather than a single independent target prediction.AvailabilityThe introduced R software package for the analysis is available in CRAN at https://cran.r-project.org/web/packages/dc3net and also at https://github.com/altayg/dc3net

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Yong Wang ◽  
Zhongyang Liu ◽  
Chun Li ◽  
Dong Li ◽  
Yulin Ouyang ◽  
...  

In this paper, we present a case study of Qishenkeli (QSKL) to research TCM’s underlying molecular mechanism, based on drug target prediction and analyses of TCM chemical components and following experimental validation. First, after determining the compositive compounds of QSKL, we use drugCIPHER-CS to predict their potential drug targets. These potential targets are significantly enriched with known cardiovascular disease-related drug targets. Then we find these potential drug targets are significantly enriched in the biological processes of neuroactive ligand-receptor interaction, aminoacyl-tRNA biosynthesis, calcium signaling pathway, glycine, serine and threonine metabolism, and renin-angiotensin system (RAAS), and so on. Then, animal model of coronary heart disease (CHD) induced by left anterior descending coronary artery ligation is applied to validate predicted pathway. RAAS pathway is selected as an example, and the results show that QSKL has effect on both rennin and angiotensin II receptor (AT1R), which eventually down regulates the angiotensin II (AngII). Bioinformatics combing with experiment verification can provide a credible and objective method to understand the complicated multitargets mechanism for Chinese herbal formula.


PLoS ONE ◽  
2012 ◽  
Vol 7 (6) ◽  
pp. e39801 ◽  
Author(s):  
Paula Vainio ◽  
John-Patrick Mpindi ◽  
Pekka Kohonen ◽  
Vidal Fey ◽  
Tuomas Mirtti ◽  
...  

2014 ◽  
Vol 15 (3) ◽  
pp. 255-271 ◽  
Author(s):  
Rubem Sadok Menna-Barreto ◽  
Kele Belloze ◽  
Jonas Perales ◽  
Floriano Silva-Jr

2018 ◽  
Vol 17 (5) ◽  
pp. 325-337 ◽  
Author(s):  
Hojjat Borna ◽  
Kasim Assadoulahei ◽  
Gholamhossein Riazi ◽  
Asghar Beigi Harchegani ◽  
Alireza Shahriary

Background & Objective: Neurodegenrative diseases are among the most widespread lifethreatening disorders around the world in elderly ages. The common feature of a group of neurodegenerative disorders, called tauopathies, is an accumulation of microtubule associated protein tau inside the neurons. The exact mechanism underlying tauopathies is not well-understood but several factors such as traumatic brain injuries and genetics are considered as potential risk factors. Although tau protein is well-known for its key role in stabilizing and organization of axonal microtubule network, it bears a broad range of functions including DNA protection and participation in signaling pathways. Moreover, the flexible unfolded structure of tau facilitates modification of tau by a wide range of intracellular enzymes which in turn broadens tau function and interaction spectrum. The distinctive properties of tau protein concomitant with the crucial role of tau interaction partners in the progression of neurodegeneration suggest tau and its binding partners as potential drug targets for the treatment of neurodegenerative diseases. Conclusion: This review aims to give a detailed description of structure, functions and interactions of tau protein in order to provide insight into potential therapeutic targets for treatment of tauopathies.


2021 ◽  
Vol 7 (3) ◽  
pp. 518-534
Author(s):  
Lauren B. Arendse ◽  
Susan Wyllie ◽  
Kelly Chibale ◽  
Ian H. Gilbert

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