Identification of GPI anchor attachment signals by a Kohonen self-organizing map.

Abstract

Anchoring of proteins to the extracytosolic leaflet of membranes via C-terminal attachment of glycosylphosphatidylinositol (GPI) is ubiquitous and essential in eukaryotes. The signal for GPI-anchoring is confined to the C-terminus of the target protein. In order to identify anchoring signals in silico, we have trained neural networks on known GPI-anchored proteins, systematically optimizing input parameters. A Kohonen self-organizing map, GPI-SOM, was developed that predicts GPI-anchored proteins with high accuracy. In combination with SignalP, GPI-SOM was used in genome-wide surveys for GPI-anchored proteins in diverse eukaryotes. Apart from specialized parasites, a general trend towards higher percentages of GPI-anchored proteins in larger proteomes was observed. GPI-SOM is accessible on-line at http://gpi.unibe.ch. The source code (written in C) is available on the same website. Positive training set, performance test sets and lists of predicted GPI-anchored proteins from different eukaryotes in fasta format.