Contextual data integration in drug discovery.
BACKGROUND
The interpretation of high-throughput profiling data depends on the pathway analysis database. Currently, pathway analysis often has to rely on a set of interactions and pathways measured in every possible human tissue, due to insufficient knowledge about interactions and pathways in the context of the profiling experiment. However, a recent global scale analysis of human tissue proteomes and interactomes reveals significant differences among tissues, suggesting that interaction and pathway data that are used out of biological context are the major source of inaccuracies and noise in the analysis of profiling data.


METHODS
In this review, the major classes of biological context used for experimental detection of molecular interactions and pathways in molecular biology are described. Furthermore, the author reviews methods for predicting biological interactions in order to evaluate the applicability of various contextual interaction data in pathway analysis. Using the results from recent publications that study large-scale tissue composition, the article provides an estimation of the gain in pathway analysis accuracy if only the interactions predicted for the context of a molecular profiling experiment are used, relative to the analysis performed with a context-independent knowledge base.


CONCLUSIONS
It is of the author's opinion that the major source of inaccuracy in pathway analysis is the lack of knowledge about tissue-specific transcriptional regulation. It is therefore suggested that the accuracy of the analysis can be substantially improved if only context-specific interactions and pathways are used for interpretation.
Elsevier, Ariadne Genomics, Inc., Rockville, MD 20878, USA. ayuryev@ariadnegenomics.com
Anton
A
Yuryev
D000818:Animals; D055808:Drug Discovery / Q000379:methods*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008967:Molecular Biology / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics