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PcPipe is a pipeline that implements a series of steps for protein clustering and annotation. 1: User defined proteins are clustered with proteins from known protein clusters. 2: Proteins that do not cluster are self-clustered to form novel protein clusters. 3: Proteins from novel self-clusters are compared to a reference set of proteins from the Similarity Matrix of Proteins (SIMAP). 4: Annotations from SIMAP proteins are assigned to each hit from the novel protein clusters.