Bioinformatics and Functional Genomics Research Group
Cancer Research Center (CiC-IBMCC, CSIC/USAL/IBSAL)
Salamanca (SPAIN)

Javier DE LAS RIVAS and Conrad DROSTE

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

Background: 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. Results: 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,, 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). Conclusions: 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.

Additional File 1: Path2enet R vignette in HTML format: Path2enet.html

Additional File 2: Path2enet R package: Path2enet_0.9.99.tar.gz

Additional File 3: Path2enet "SQL dump file" to create a MySQL database with all human pathways:

[ARTICLE published in BMC Genomics 2016]