SecretePipe: a screening pipeline for secreted proteins with competence to identify potential membrane-bound shed...

The identification of secreted protein markers has been receiving great attention as part of the trend toward noninvasive biomarker discovery. In addition, certain cell membrane proteins are known to be released into the extracellular milieu via ectodomain shedding. As membrane proteins play an essential role in signaling pathways and because most of the cancer biomarkers approved by the FDA today are membrane shed proteins, a tool that can correctly predict these class shed proteins is valuable. In this study, an in-house predictor, ShedP, was developed to predict the ectodomain shedding events of membrane proteins. ShedP is the first computational method to our knowledge to allow shed membrane protein prediction. By integrating ShedP with other state-of-the-art predictors, a screening pipeline, SecretePipe, has been created that is able to identify secreted nonmembrane proteins on the basis of signal peptides and to identify released membrane proteins on the basis of ectodomain shedding. The predictive results using secretome data sets revealed that SecretePipe outperformed other state-of-the-art secreted protein predictors. When evaluated against released membrane proteins, SecretePipe performed better than other predictors in identifying membrane-bound released proteins due to the presence of ShedP. SecretePipe showed a great potential in assisting the identification of membrane-bound shed markers in biomarker discovery.