Flow chart depicting the annotation pipeline implemented in this study. Sequence based methods are employed first (top), domains that elude primary sequence based methods are predicted by structure-prediction methods (bottom). For any given genome, data from all levels in this method hierarchy are integrated using SBEAMS (Systems Biology Experiment Analysis and Management System). Implicit in this annotation hierarchy is the idea that protein annotation should be domain-centric (that is, multi-domain proteins should be divided into domains as early as possible in the annotation process). SBEAMS produces a table of annotations where for a given domain only results from the topmost level in the method hierarchy (PDB-BLAST → Pfam → Rosetta) producing a significant hit are displayed.