O-3: Drug Repositioning by Merging Gene Expression Data Analysis and Cheminformatics Target Prediction Approaches
Authors
Abstract:
The transcriptional responses of drug treatments combined with a protein target prediction algorithm was utilised to associate compounds to biological genomic space. This enabled us to predict efficacy of compounds in cMap and LINCS against 181 databases of diseases extracted from GEO. 18/30 of top drugs predicted for leukemia (e.g. Leflunomide and Etoposide) and breast cancer (e.g. Tamoxifen and Ouabain) were already proven effective. LC50 of a predict compound, Fenbendazole, on HL60 and BMSC cell lines was experimentally evaluated to be 127nM and 5066nM (48hrs). Novel predicted drugs for differentiating stem cells to cardiomyocytes such as Famotidine enhanced expansion rate and heart-beat strength of Embryoid Bodies and expression of cardiac precursor markers(Nkx2-5, Gata4, Mef2c) and cardiac markers(Actc1, Tagln, Myh6) considerably during and post cardiac progenitor cell (CPC) formation. Combining target prediction with gene expression analysis enabled us to predict effective compounds and targets for diseases and differentiation of stem cells.
similar resources
Prediction of Drug-Target Interactions for Drug Repositioning Only Based on Genomic Expression Similarity
Small drug molecules usually bind to multiple protein targets or even unintended off-targets. Such drug promiscuity has often led to unwanted or unexplained drug reactions, resulting in side effects or drug repositioning opportunities. So it is always an important issue in pharmacology to identify potential drug-target interactions (DTI). However, DTI discovery by experiment remains a challengi...
full textPrediction of blood cancer using leukemia gene expression data and sparsity-based gene selection methods
Background: DNA microarray is a useful technology that simultaneously assesses the expression of thousands of genes. It can be utilized for the detection of cancer types and cancer biomarkers. This study aimed to predict blood cancer using leukemia gene expression data and a robust ℓ2,p-norm sparsity-based gene selection method. Materials and Methods: In this descriptive study, the microarray ...
full textPrediction of Drug-Target Interactions and Drug Repositioning via Network-Based Inference
Drug-target interaction (DTI) is the basis of drug discovery and design. It is time consuming and costly to determine DTI experimentally. Hence, it is necessary to develop computational methods for the prediction of potential DTI. Based on complex network theory, three supervised inference methods were developed here to predict DTI and used for drug repositioning, namely drug-based similarity i...
full textCan Survival Prediction Be Improved By Merging Gene Expression Data Sets?
BACKGROUND High-throughput gene expression profiling technologies generating a wealth of data, are increasingly used for characterization of tumor biopsies for clinical trials. By applying machine learning algorithms to such clinically documented data sets, one hopes to improve tumor diagnosis, prognosis, as well as prediction of treatment response. However, the limited number of patients enrol...
full textComputational Discovery of Putative Leads for Drug Repositioning through Drug-Target Interaction Prediction
De novo experimental drug discovery is an expensive and time-consuming task. It requires the identification of drug-target interactions (DTIs) towards targets of biological interest, either to inhibit or enhance a specific molecular function. Dedicated computational models for protein simulation and DTI prediction are crucial for speed and to reduce the costs associated with DTI identification....
full textComparison of Merging and Meta-Analysis as Alternative Approaches for Integrative Gene Expression Analysis
An increasing amount of microarray gene expression data sets is available through public repositories. Their huge potential in making new findings is yet to be unlocked by making them available for large-scale analysis. In order to do so it is essential that independent studies designed for similar biological problems can be integrated, so that new insights can be obtained. These insights would...
full textMy Resources
Journal title
volume 8 issue 2.5
pages 18- 18
publication date 2014-07-01
By following a journal you will be notified via email when a new issue of this journal is published.
Hosted on Doprax cloud platform doprax.com
copyright © 2015-2023