The presence of signal peptide in the query sequence complicates the transmembrane (TM) topology prediction because the hydrophobic core of signal peptide is easily predicted as the putative first TM segment (Lao and Shimizu, 2001). In genome wide analyses, the likely signal peptide region is treated in several ways. It was either masked out from topological calculations (Jones, 1998) or omitted (Arkin et.al., 1997; Stevens and Arkin, 2000) when picked up as the first TM segment by the TM topology prediction method within a specified region from the N-terminal. One treatment simply avoided the signal peptide by considering a minimum number of predicted TM segments for further analysis (Wallin and von Heijne, 1998), while another treated the signal peptide directly by removing it first from the query sequence before performing prediction analysis by the TM topology prediction method (Kihara and Kanehisa, 2000). However, in a recent paper by (Krogh et al., 2001) the signal peptide was removed only after the prediction of TM helices.
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