Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.

Thousands of interactions assemble proteins into modules that impart spatial and functional organization to the cellular proteome. Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks. The first, BioPlex 3.0, results from affinity purification of 10,128 human proteins-half the proteome-in 293T cells and includes 118,162 interactions among 14,586 proteins. The second results from 5,522 immunoprecipitations in HCT116 cells. These networks model the interactome whose structure encodes protein function, localization, and complex membership. Comparison across cell lines validates thousands of interactions and reveals extensive customization. Whereas shared interactions reside in core complexes and involve essential proteins, cell-specific interactions link these complexes, "rewiring" subnetworks within each cell's interactome. Interactions covary among proteins of shared function as the proteome remodels to produce each cell's phenotype. Viewable interactively online through BioPlexExplorer, these networks define principles of proteome organization and enable unknown protein characterization.

UniProtExtractR: an app and R package for easily extracting protein-specific UniProtKB information and fine-tuning organelle resolution.

Summary: UniProtKB is a publicly accessible database of annotated protein features for numerous organisms; however, globally extracting protein entry information for data visualization and categorization can be challenging. While the UniProtKB entry syntax maintains database consistency, it simultaneously obscures key terms within long character strings. To increase accessibility, UniProtExtractR is both an app and R package that extracts desired information across nine UniProtKB categories: DNA binding, Pathway, Transmembrane, Signal peptide, Protein families, Domain [FT], Motif, Involvement in disease, and Subcellular location [CC]. The app features interactive frequency tables that globally summarize both the original UniProtKB input query as well as the extracted/changed entry values. Moreover, UniProtExtractR includes a tractable mapping algorithm to define custom organelle-level resolution. UniProtExtractR exists as a freely accessible Shiny app that requires no coding experience as well as R package, the code of which is entirely open source. Availability and implementation: UniProtExtractR source code and user manual, including example files and troubleshooting, is available at https://github.com/alex-bio/UniProtExtractR. The Shiny app is hosted at https://harperlab.connect.hms.harvard.edu/uniprotextractR.