Path2enet: generation of human pathway-derived networks in an expression specific context

Conrad Droste, Javier De Las Rivas

Biological pathways are subsets of the complex biomolecular wiring that occur in living cells. They are usually rationalized and depicted in cartoon maps or charts to show them in a friendly visible way. Despite these efforts to present biological pathways, the current progress of bioinformatics indicates that translation of pathways in networks can be a very useful approach to achieve a computer-based view of the complex processes and interactions that occurr in a living system. We have developed a bioinformatic tool called Path2enet that provides a translation of biological pathways in protein networks integrating several layers of information about the biomolecular nodes in a multiplex view. Path2enet is an R package that reads the relations and links between proteins stored in a comprehensive database of biological pathways, KEGG (Kyoto Encyclopedia of Genes and Genomes, http://www.genome.jp/kegg/ ), and integrates them with expression data from various resources and with data on protein-protein physical interactions. Path2enet tool uses the expression data to determine if a given protein in a network (i.e., a node) is active (ON) or inactive (OFF) in a specific cellular context or sample type. In this way, Path2enet reduces the complexity of the networks and reveals the proteins that are active (expressed) under specific conditions. As a proof of concept, this work presents a practical "case of use" generating the pathway-expression-networks corresponding to the NOTCH Signaling Pathway in human B- and T-lymphocytes. This case is produced by the analysis and integration in Path2enet of an experimental dataset of genome-wide expression microarrays produced with these cell types (i.e., B cells and T cells). Path2enet is an open source and open access tool that allows the construction of pathway-expression-networks, reading and integrating the information from biological pathways, protein interactions and gene expression cell specific data. The development of this type of tools aims to provide a more integrative and global view of the links and associations that exist between the proteins working in specific cellular systems.