Cross-talk quantification in molecular networks with application to pathway-pathway and cell-cell interactions

Abstract

MotivationsDisease phenotypes are interpreted as the consequence of interactions among molecular processes affected by a series of molecular alterations. Current omics approaches underline the importance of such interactions, focusing on molecular mechanisms, by using manually curated pathways or gene sets. As there are no clear boundaries between gene sets, cross-talks between them are relevant to investigate disease phenotypes.Here we present Ulisse, a method to (1) quantify cross-talks between gene sets, with application to pathways and intercellular cross-talks; (2) investigate the role of the genes involved in cross-talks, via functional relevance analysis, in terms of regulated processes/cell types. As a proof-of-concept, we studied pathway and cell-cell cross-talks in normal and tumoral breast samples, and compared the obtained results with other available tools: PathNet for pathway cross-talk, ICELLNET and SingleCellSignalR for intercellular cross-talk.ResultsCross-talk analysis allowed to identify dysregulated interactions between tumor progression key mechanisms, while intercellular cross-talks describe well-known interactions of the tumor with the microenvironment. Through functional relevance analysis, Ulisse was able to pinpoint well known key players of the tumor, as well as potential therapeutic targets. The comparison of Ulisse to other packages highlighted the good performance of our package. In conclusion, Ulisse proved to be a valuable tool to study cross-talks, and provide a newly implemented approach to analyse involved genes.Availability and implementationUlisse is an R package and available athttps://github.com/emosca-cnr/UlisseContactettore.mosca@itb.cnr.itSupplementary informationLink to supplementary tables + reference to on-line supplementary material