Analysis of gene enrichment and drug correlations revealed strong connections to ribosomal biogenesis nucleoli and translation initiation.
The comparison of the data sets only establishes correlation, not causation, and if many of the correlations are the result of relatively non-specific factors, or the causative gene(s) co-varies with many others in the dataset, large gene expression patterns reflecting physiology unresolved by the sampling of cell lines in the NCI60 may obscure causative gene:drug correlations.
Other domain-specific ontologies have also been developed, including pharmacogenomics [14], ligand protein interaction [15, 16], Disease-Drug Correlation Ontology (DDCO) [17], biological pathways (BioPAX) [18], Translational Medicine Ontology [19] and neuromedicine (SWAN) [20].
In our gene-drug correlation analyses, gemcitabine consistently belonged to an isolated cluster in a reproducible fashion.
In order to analyze the relationship between gene expression and drug activity, we generated the gene-drug correlation matrix [AT] (correlation coefficient) in which the rows represent the genes and the columns represent the drugs.
Since the GI50 value is represented the drug's chemo-activity, the gene-drug correlation is established based on the correlation of gene expression and drug activity across 60 cell lines.
Microarray transcript expression studies of the 60 cell lines reveal, for example, a gene-drug correlation with potential clinical implications – that between the asparagine synthetase gene and the enzyme-drug L-asparaginase in ovarian cancer cells.
A total design approach to cancer chemotherapy through the gene-drug correlations using NCI program may yield improved therapeutic options.
The gene-drug correlations using NCI program in these study may be a valuable tool for the identification of determinants of anticancer drug activity in tumors and for the design of cancer chemotherapy.
Although they can be induced by anti-parkinsonian drugs, correlations between use of these agents and presence of hallucinations are actually relatively weak, and instead cognitive impairment has been shown to be the major risk factor, indicating that they are a core symptom of the dementing process (Fénelon et al., 2000; Williams and Lees, 2005).
For these drugs, lower correlation with the drug signature corresponded to a lower rate of survival.
