IMAT-ITCR Collaboration: A Cytoscape Toolkit to Model Proteoform-Resolved Cancer Networks

ABSTRACT A single gene can give rise to several alternatively spliced protein isoforms (i.e., proteoforms) that acquire cancer-promoting functions. These cancer-associated proteoforms, compared to their normal counterparts, can

exhibit differential binding to protein partners that lead to the “rewiring” of cellular networks. To derive insight into cancer cellular systems, network biology tools, such as Cytoscape, has been developed to visualize and analyze cancer from a network biology framework. However, the molecular diversity of proteoforms is not

reflected in cancer interactome models. A limitation to progress in this area is conceptually simple. In nearly all a biological network models, ‘nodes’ represent proteins and ‘edges’ connect pairs of proteins that exhibit a functional interaction. This is a problem because a gene may have a canonical annotated function, but the

cancer-associated proteoform can exhibit entirely different functions. Rather than conflating all proteoforms into one gene representation, in this proposal, the IMAT and ITCR team will create a formal representation of proteoforms in a network biology framework, based on the Cytoscape eXchange (CX) schema that underlies

all NDEx network resources. At the project’s end, the IMAT and ITCR teams will release the new proteoform data specification (PCX), proteoform networks in the public NDEx database, and an NDEx-compatible Cytoscape web analysis module based on PCX to analyze proteoform networks. This project will catalyze new

end-user applications that the NDEx resource will serve, as well as provide for the IMAT team advanced network analysis that can be performed on experimentally generated cancer interactomes.