The presence of signal peptide significantly affects transmembrane topology prediction

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. The next question now is how to treat best the signal peptide—removing it before or after performing prediction analysis? At this time, however, there are no published papers regarding this aspect. Thus, it would be helpful and appropriate to conduct a study that addresses this issue to determine which of the two treatments for signal peptide is best. Moreover, knowing the extent of influence of the presence of signal peptide, as well as transit peptide, on the prediction performance of TM topology prediction methods is equally important. In this paper, we were able to show the effect of the presence of signal peptide on ten selected TM topology prediction methods by the different prediction accuracy ratings obtained if the signal peptide region in the query sequence is left untreated (remain), or treated (removed) either before or after performing prediction analysis.