Title
Computational approaches for drug repositioning and combination therapy design.
Abstract
Heterogeneous high-throughput biological data become readily available for various diseases. The amount of data points generated by such experiments does not allow manual integration of the information to design the most optimal therapy for a disease. We describe a novel computational workflow for designing therapy using Ariadne Genomics Pathway Studio software. We use publically available microarray experiments for glioblastoma and automatically constructed ResNet and ChemEffect databases to exemplify how to find potentially effective chemicals for glioblastoma--the disease yet without effective treatment. Our first approach involved construction of signaling pathway affected in glioblastoma using scientific literature and data available in ResNet database. Compounds known to affect multiple proteins in this pathway were found in ChemEffect database. Another approach involved analysis of differential expression in glioblastoma patients using Sub-Network Enrichment Analysis (SNEA). SNEA identified angiogenesis-related protein Cyr61 as the major positive regulator upstream of genes differentially expressed in glioblastoma. Using our findings, we then identified breast cancer drug Fulvestrant as a major inhibitor of glioblastoma pathway as well as Cyr61. This suggested Fulvestrant as a potential treatment against glioblastoma. We further show how to increase efficacy of glioblastoma treatment by finding optimal combinations of Fulvestrant with other drugs.
Year
DOI
Venue
2010
10.1142/S0219720010004732
J. Bioinformatics and Computational Biology
Keywords
Field
DocType
systems biology,drug repositioning
Combination therapy,Regulator,Biological data,Drug repositioning,Microarray,Biology,Systems biology,Genomics,Bioinformatics,Fulvestrant
Journal
Volume
Issue
ISSN
8
3
1757-6334
Citations 
PageRank 
References 
12
0.75
4
Authors
4
Name
Order
Citations
PageRank
Ekaterina Kotelnikova1542.66
Anton Yuryev219112.14
Ilya Mazo326514.76
Nikolai Daraselia433219.57