CIRFESS: An Interactive Resource for Querying the Set of Theoretically Detectable Peptides for Cell Surface and Extracellular Enrichment Proteomic Studies

Cell
surface transmembrane, extracellular, and secreted proteins
are high value targets for immunophenotyping, drug development, and
studies related to intercellular communication in health and disease.
As the number of specific and validated affinity reagents that target
this subproteome are limited, mass spectrometry (MS)-based approaches
will continue to play a critical role in enabling discovery and quantitation
of these molecules. Given the technical considerations that make MS-based
cell surface proteome studies uniquely challenging, it can be difficult
to select an appropriate experimental approach. To this end, we have
integrated multiple prediction strategies and annotations into a single
online resource, Compiled Interactive Resource for Extracellular
and Surface Studies (CIRFESS). CIRFESS
enables rapid interrogation of the human proteome to reveal the cell
surface proteome theoretically detectable by current approaches and
highlights where current prediction strategies provide concordant
and discordant information. We applied CIRFESS to identify the percentage
of various subsets of the proteome which are expected to be captured
by targeted enrichment strategies, including two established methods
and one that is possible but not yet demonstrated. These results will
inform the selection of available proteomic strategies and development
of new strategies to enhance coverage of the cell surface and extracellular
proteome. CIRFESS is available at www.cellsurfer.net/cirfess.