Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0017636 (
glioblastoma
)
18,345
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:Computational approaches for drug repositioning and combination therapy design. 2055 64
