INTRODUCTION This Web Service implements NetCTL v. 1.1. 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: An integrative approach to CTL epitope prediction. A combined algorithm integrating MHC-I binding, TAP transport efficiency, and proteasomal cleavage predictions. Larsen MV, Lundegaard C, Kasper Lamberth, Buus S. Brunak S, Lund O, and Nielsen M. European Journal of Immunology 35(8): 2295-303, 2005 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 firstname.lastname@example.org 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 email@example.com 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, B7, B8, B27, B44, B58 and B62; * 'wcle' - weight on C terminal cleavage The value 0.1 gives optimal predictive performance on the average. * 'wtap' - weight on TAP transport efficiency The value 0.05 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) * 'sequences' - protein sequences, with unique identifiers 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: 'output' - prediction results For each input residue a record is output consisting of the following fields: seqname truncated to 12 characters in ver. 1.1a source "netCTL-1.1" (fixed string) feature "CTL" (fixed string) start,end residue number (given twice) score prediction score (combined) strand,frame N/A comment Text string consisting of: * Predicted MHC binding affinity The value is give as 1 - log50k(aff), where log50k is the logaritm with base 50.000, and aff is the affinity in nM units; * Rescaled binding affinity The predicted binding affinity is normalized by the 1% fractil * C terminal cleavage affinity * TAP transport efficiency "-E" to indicate the identified MHC ligands (when the combined score is greater than the threshold). CONTACT Questions concerning the scientific aspects of the NetCTL method should go to Morten Nielsen, firstname.lastname@example.org; technical question concerning the Web Service should go to Peter Fischer Hallin, email@example.com or Kristoffer Rapacki, firstname.lastname@example.org.
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