Protein Engineering, Vol. 15, No. 9, 745-752,
September 2002
© 2002 Oxford University Press
On filtering false positive transmembrane protein predictions
1 University of Birmingham, School of Biosciences, Edgbaston, Birmingham B15 2TT, UK, 3 IMP Bioinformatics, Dr Bohr-Gasse 7, A-1030 Vienna, Austria and 4 Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, P.O. Box 7, H-1518 Budapest, Hungary
While helical transmembrane (TM) region prediction tools achieve high (>90%) success rates for real integral membrane proteins, they produce a considerable number of false positive hits in sequences of known nontransmembrane queries. We propose a modification of the dense alignment surface (DAS) method that achieves a substantial decrease in the false positive error rate. Essentially, a sequence that includes possible transmembrane regions is compared in a second step with TM segments in a sequence library of documented transmembrane proteins. If the performance of the query sequence against the library of documented TM segment-containing sequences in this test is lower than an empirical threshold, it is classified as a non-transmembrane protein. The probability of false positive prediction for trusted TM region hits is expressed in terms of E-values. The modified DAS method, the DAS-TMfilter algorithm, has an unchanged high sensitivity for TM segments (
95% detected in a learning set of 128 documented transmembrane proteins). At the same time, the selectivity measured over a non-redundant set of 526 soluble proteins with known 3D structure is 99%, mainly because a large number of falsely predicted single membrane-pass proteins are eliminated by the DAS-TMfilter algorithm.
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