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the European Bioinformatics Institute (EBI) [6] as cross-validation set. We applied the hydrophobicity scale of Kyte and Doolittle [5], and measured performance ...
Genome Informatics 12: 340–342 (2001)

340

Methods for Detecting the Signal Peptide in Transmembrane and Globular Proteins Demelo Madrazo Lao

Toshio Shimizu

[email protected]

[email protected]

Department of Information Science, Graduate School of Science, Hirosaki University, Hirosaki 036-8561, Japan

Keywords: signal peptide, signal peptide discrimination, signal peptide detection, average hydrophobicity

1

Introduction

Signal peptides (SP) play an important role in protein transport and sorting to the different compartment of the cell. Although SPs have varying lengths and do not have a consensus sequence, almost all possess a common three-region structure: the positively charged n-region, the hydrophobic h-region, and the c-region where the cleavage site occurs [7]. The presence of an SP in the sequence, if not properly addressed, affects the prediction accuracy of a membrane topology prediction method. For instance, in a recently published results of complete genomes’ analysis, the discrimination performance between soluble and membrane proteins drops when SPs are present [4]. Among transmembrane (TM) proteins, the effect becomes evident when predicting for the TM topology because almost all TM prediction methods have the tendency to predict SP as the first TM segment (paper under review). Thus, here, we present two methods, one to discriminate between a putative first TM segment and an SP among TM proteins, and the other one to detect the presence of an SP among globular proteins. The first method applies two discrimination parameters: the position of the first upstream charged residue scanned from the maximal average hydrophobicity region and the average hydrophobicity computed from a fixed number of residue positions from the N-terminal. The second method uses a combination of the occurrence of an uncharged region and the peak average hydrophobocity and its location.

2

Method and Results

We used reference and cross-validation sets. The reference set was used to determine the appropriate cut-off values for our methods while the cross-validation set was used to validate the performance of the methods. For the non-redundant (

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