Integrating Protein Localization with Automated Signaling Pathway Reconstruction

Understanding cellular responses via signal transduction is a core focus in systems biology. Tools to automatically reconstruct signaling pathways from protein-protein interactions (PPIs) can help biologists generate testable hypotheses about signaling. However, automatic reconstruction of signaling pathways suffers from coarsely-weighted interactions, leading to many equally good candidates. Further, some reconstructions are biologically misleading due to ignoring protein localization information. We propose LocPL, a method to improve the automatic reconstruction of signaling pathways from PPIs by incorporating information about protein localization in the reconstructions. LocPL produces more accurate and biologically meaningful reconstructions on a versatile set of signaling pathways. The code, including a newly-released interactome PLNet
₂
, is available at https://github.com/annaritz/localized-pathlinker.