INTRODUCTION This Web Service implements NetCTL v. 1.2.ws0. It predicts CTL epitopes in protein sequences integrating prediction of peptide MHC binding, proteasomal C terminal cleavage and TAP transport efficiency. The method is described in detail in the following article: Large-scale validation of methods for cytotoxic T-lymphocyte epitope prediction. Larsen MV, Lundegaard C, Lamberth K, Buus S, Lund O, Nielsen M. BMC Bioinformatics. Oct 31;8:424. 2007 Alongside this Web Service the NetCTL method is also implemented as a traditional click-and-paste WWW server at: http://www.cbs.dtu.dk/services/NetCTL/ NetCTL is also available as a stand-alone software package; write to software@cbs.dtu.dk for details. NetCTL is also available as a stand-alone software package to install and run at the user's site, with the same functionality. For academic users there is a download page at: http://www.cbs.dtu.dk/cgi-bin/nph-sw_request?netCTL Other users are requested to write to software@cbs.dtu.dk for details. WEB SERVICE OPERATION This Web Service is fully asynchronous; the usage is split into the following three operations: 1. runService Input: The following parameters and data: * 'supertype' HLA supertype. 10 HLA supertypes are available: A1, A2, A3, A24, A26, B7, B8, B27, B39, B44, B58 and B62; * 'wtap weight on TAP transport efficiency. The value 0.05 gives optimal predictive performance on the average; * 'wMHC' weight on MHC; * 'wcle' weight on C terminal cleavage. The value 0.1 gives optimal predictive performance on the average; * 'threshold' threshold for epitope identification. Peptides with a combined prediction score value greater than the threshold value are marked as potential epitopes. In a large scale benchmark identifying known CTL epitope in proteins the default value of 0.75 was found to correspond to a sensitivity of 0.65 and a specificity 0.97. Note that the benchmark is highly unbalanced since only one peptide is identified as CTL epitope in each protein, and the number of negatives hence is orders of magnitude larger than the number of positives. This has important implications for the interpretation of the specificity values. * 'sort' output sorting on score. Possible values are 0 (sorting on the combined score), 1 (MHC), 2 (Cle), 3 (TAP) and negative (no sorting); * 'sequencedata' mulitple elements of type 'sequence': * 'sequence' answers to one sequence: * 'id' unique identifier for the sequence; * 'comment' optional comment; * 'seq' protein sequence. The sequence must be written using the one letter amino acid code: `acdefghiklmnpqrstvwy' or `ACDEFGHIKLMNPQRSTVWY'. Other letters will be converted to `X' and treated as unknown amino acids. Other symbols, such as whitespace and numbers, will be ignored. Output: Unique job identifier 2. pollQueue Input: Unique job identifier Output: 'jobstatus' - the status of the job Possible values are QUEUED, ACTIVE, FINISHED, WAITING, REJECTED, UNKNOWN JOBID or QUEUE DOWN 3. fetchResult Input: Unique job identifier of a finished job Output: * 'annsource' 'method' name of the method, here always 'NetCTL'; 'version' version of the method: here always '1.2 ws0'; 'ann' annotations - one element per input sequence; 'sequence' standard sequence object; 'id' sequence identifier; 'annrecords/annrecord' 'feature' feature name, here always 'NetCTL'; 'range' always present, indicates the range in the sequence: 'begin' begin position; 'end' end position; 'score' 'key'='aff' predicted MHC binding affinity. 'value' score value for 'aff'. The value is given as 1 - log50k(aff), where log50k is the logaritm with base 50.000, and aff is the affinity in nM units; 'score' 'key'='aff_rescale' rescale binding affinity; 'value' score value for 'aff_rescale'. The predicted binding affinity is normalized by the 1% fractil; 'score' 'key'='cle' C terminal cleavage affinity; 'value' score value for 'cle'; 'score' 'key'='tap' TAP transport efficiency; 'value' score value for 'tap'; 'score' 'key'='COMB' prediction score; 'value' score value for 'COMB'; 'comment' gives 'E' for identified MHC ligands (when the combined score is greater than the threshold). More comprehensive information about the output could be found at: http://www.cbs.dtu.dk/services/NetCTL/ CONTACT Questions concerning the scientific aspects of the NetCTL method should go to Morten Nielsen, mniel@cbs.dtu.dk; technical question concerning the Web Service should go to Karunakar Bayyapu, karun@cbs.dtu.dk or Kristoffer Rapacki, rapacki@cbs.dtu.dk.