MSF: Modulated Sub-graph Finder

High throughput techniques such as RNA-seq or microarray analysis have proven to be invaluable for the characterization of global transcriptional gene activity changes due to external stimuli or diseases. Differential gene expression analysis (DGEA) is the first step in the course of data interpretation, typically producing lists of dozens to thousands of differentially expressed genes. To further guide the interpretation of these lists, different pathway analysis approaches have been developed. These tools typically rely on the classification of genes into sets of genes, such as pathways, based on the interactions between the genes and their function in a common biological process. Regardless of technical differences, these methods do not properly account for cross talk between different pathways and rely on binary separation into differentially expressed gene and unaffected genes based on an arbitrarily set p-value cut-off. To overcome this limitation, we developed a novel approach to identify concertedly modulated sub-graphs in the global cell signaling network, based on the DGEA results of all genes tested. Thereby, expression patterns of genes are integrated according to the topology of their interactions and allow potentially to read the flow of information from the perturbation source to the effectors. The described software, named Modulated Sub-graph Finder (MSF) is freely available at https: //github.com/Modulated-Subgraph-Finder/MSF.