Background: Small molecule effects can be represented by active signaling pathways within functional networks. Identifying these can help to design new strategies to utilize known small molecules, e.g. to trigger specific cellular transformations or to reposition known drugs.
Results: We developed CellFateScout that uses the method of Latent Variables to turn differential high-throughput expression data and a functional network into a list of active signaling pathways. Applying it to Connectivity Map data, i.e., differential expression data describing small molecule effects, we then generated a Human Small Molecule Mechanisms Database. Finally, using a list of active signaling pathways as query, a similarity search can identify small molecules from the database that may trigger these pathways. We validated our approach systematically, using expression data of small molecule perturbations, yielding better predictions than popular bioinformatics tools.
Conclusions: CellFateScout can be used to select small molecules for their desired effects. The CellFateScout Cytoscape plugin, a tutorial and the Human Small Molecule Mechanisms Database are available at https://sourceforge.net/projects/cellfatescout/ under LGPLv2 license.