FunHoP: Enhanced Visualization and Analysis of Functionally Homologous Proteins in Complex Metabolic Networks

Cytoscape is often used for visualization and analysis of metabolic pathways. For example, based on KEGG data, a reader for KEGG Markup Language (KGML) is used to load files into Cytoscape. However, although multiple genes can be responsible for the same reaction, the KGML-reader KEGGScape only presents the first listed gene in a network node for a given reaction. This can lead to incorrect interpretations of the pathways. Our new method, FunHoP, shows all possible genes in each node, making the pathways more complete. FunHoP collapses all genes in a node into one measurement using read counts from RNA-seq. Assuming that activity for an enzymatic reaction mainly depends upon the gene with the highest number of reads, and weighting the reads on gene length and ratio, a new expression value is calculated for the node as a whole. Differential expression at node level is then applied to the networks. Using prostate cancer as model, we integrate RNA-seq data from two patient cohorts with metabolism data from literature. Here we show that FunHoP gives more consistent pathways that are easier to interpret biologically. Code and documentation for running FunHoP can be found at https://github.com/kjerstirise/FunHoP.