NetCTL - 1.2

Predection of CTL epitopes in protein sequences

The NetCTL 1.2 server predicts CTL epitopes in protein sequences. The current version 1.2 is an update to the version 1.0. Version 1.2 expands the MHC class I binding predicition to 12 MHC supertypes including the supertypes A26 and B39. The accuracy of the MHC class I peptide binding affinity is significantly improved compared to the earlier version. Also the prediction of proteasonal cleavage has been improved and is now identical to the predictions obtained by the NetChop-3.0 server. The updated version has been trained on a set of 886 known MHC class I ligands.

NOTE. On Aug 16 2006 a minor update to the server has been implemented improving the prediction accuracy for MHC binding. The earlier version of the NetCTL 1.2 server (1.2 beta) is available via the versions history for the server.

The method integrates prediction of peptide MHC class I binding, proteasomal C terminal cleavage and TAP transport efficiency. The server allows for predictions of CTL epitopes restricted to 12 MHC class I supertype. MHC class I binding and proteasomal cleavage is performed using artificial neural networks. TAP transport efficiency is predictied using weight matrix.

The MHC peptide binding is predicted using neural networks trained as described for the NetMHC server. The proteasome cleavage event is predicted using the version of the NetChop neural networks trained on C terminals of known CTL epitopes as describe for the NetChop-3.0 server. The TAP transport efficiency is predicted using the weight matrix based method describe by Peters et al.

The server includes predictions of MHC/peptide binding for 12 MHC class I supertypes. The output from the neural network predicting MHC/peptide binding is a log transformed value related to the IC50 values in nM units. For details on the transformation please see the Output format

The scores from the three individual prediction methods are integrated as a weighted sum with a relative weight on peptide/MHC binding of 1. Different thresholds for the integrated score can be translated into sensitivity/specificity values. In a large benchmark calculate containing more than 800 known MHC class I ligands the following relations were found

Score Sensitivity Specificity
> 1.25 0.54 0.993
> 1.00 0.70 0.985
> 0.90 0.74 0.980
> 0.75 0.80 0.970
> 0.50 0.89 0.940

The project is collaboration between CBS and IMMI at Copenhagen university


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