Morten Nielsen

..This reflects a significant gap in knowledge as HLA DP and DQ molecules are presumably equally important, and have only been studied less because they are more difficult to handle experimentally...

..Characterizing each MHC-II molecule using peptide-screening binding assays is hence not a viable option...

..The human MHC class I system (HLA-I) is extremely polymorphic. The number of registered HLA-I molecules has now surpassed 1500. Characterizing the specificity of each separately would be a major undertaking...

..Furthermore, the pan-specific methods have been used to make a graphical atlas such as the MHCMotifviewer, which allows for visual comparison of specificities of different alleles...

..e., the specificity of TAP has evolved to fit the specificity of the proteasome. This evolutionary relationship allows for a more efficient antigen presentation...

....

....

..Finally, we use the method to predict T-cell epitopes for the genome of hepatitis C virus and discuss possible applications of the prediction method to guide the process of rational vaccine design...

..The predictive performance of the method is validated on a large MHC class II benchmark data set covering 14 HLA-DR (human MHC) and three mouse H2-IA alleles...

..The calculation demonstrates that the predictive performance of the Gibbs sampler is higher than that of ClustalW and in most cases also higher than that of the TEPITOPE method...

..The high performance of NetMHCpan-2.0 for non-human primates documents the method's ability to provide broad allelic coverage also beyond human MHC molecules. The method is available at http://www.cbs.dtu.dk/services/NetMHCpan...

..Finally, it should be noted that data selection strategies similar to those used here might be of use in other settings in which generation of more data is a costly process...

..The MHC motif viewer is available at http://www.cbs.dtu.dk/biotools/MHCMotifViewer/ ...

..The final method, NetMHCcons, is publicly available at www.cbs.dtu.dk/services/NetMHCcons , and allows the user in an automatic manner to obtain the most accurate predictions for any given MHC molecule...

....

..Supplementary material is available at http://www.cbs.dtu.dk/researchgroups/immunology/supertypes.html...

..Here, we develop such large-scale benchmark and corresponding performance measures and report the performance of an updated version 1.2 of NetCTL in comparison with the four other methods...

..These pan-specific human lymphocyte antigen (HLA) predictors have not previously been compared using independent evaluation sets...

..Here, the performance is further validated and benchmarked using a large set of newly published affinity data, non-redundant to the training set. The server is free of use and available at: http://www.cbs.dtu.dk/services/NetMHC...

..AVAILABILITY: The algorithm has been implemented in the web-accessible servers NetMHC-3.0: http://www.cbs.dtu.dk/services/NetMHC-3.0, and NetMHCpan-1.1: http://www.cbs.dtu.dk/services/NetMHCpan-1.1..

....

..The method is available at http://www.cbs.dtu.dk/services/NetCTL. Supplementary material is available at http://www.cbs.dtu.dk/suppl/immunology/CTL.php...

..In summary, these findings strongly suggest that local structural properties influence antigen processing and/or the accessibility of peptides to the MHC class II molecule...

..Presentation of peptides on Major Histocompatibility Complex (MHC) molecules is the cornerstone in immune system activation and increased knowledge of the characteristics of MHC ligands and their source proteins is highly desirable...

..This study demonstrates how integration of diverse algorithmic approaches can lead to improved prediction. The method may also be used for making ligand-binding predictions for other types of receptors where many variants exist...

..All three peptides that elicited responses had an HLA binding affinity of 2 nM or less. The results indicate the importance of the strength of HLA binding in shaping the immune response...

..Thus, HLArestrictor should be a valuable tool in any T cell epitope discovery process aimed at identifying new epitopes from infectious diseases and other disease models...

..Selected potential epitopes were all evaluated experimentally using ex vivo assays...

..We expect prediction methods as well as experimental validation methods to continue to develop and that we will soon see clinical trials of products whose development has been guided by prediction methods...

..We conclude that this new generation of epitope discovery systems has become a highly efficient tool for epitope discovery, and recommend that the less accurate prediction systems of the past be abandoned, as these are obsolete...

..The method and benchmark datasets are available at http://www.cbs.dtu.dk/services/NetCTLpan/...

..Beside its accuracy, one of the important features of the method is its speed. For most queries, the response time of the server is <20 min. The web server is available at http://www.cbs.dtu.dk/services/CPHmodels/...

..West Nile virus (WNV) is a growing threat to public health and a greater understanding of the immune response raised against WNV is important for the development of prophylactic and therapeutic strategies...

..Conversely, the binding motifs for DQ molecules appear more divergent, displaying unconventional anchor positions and in some cases rather unspecific amino acid preferences...

..We have successfully applied this method to several different data sets including peptide microarray-derived sets containing more than 100,000 data points. NNAlign is available online at http://www.cbs.dtu.dk/services/NNAlign...

..This work underlines the importance of bioinformatics as a resource-saving tool in the field of epitope discovery. In addition, the data can be used to benchmark the performance of other new or existing CTL epitope-prediction tools...

..The output from the server is a sequence logo and a PSSM. Seq2Logo is available at http://www.cbs.dtu.dk/biotools/Seq2Logo (14 May 2012, date last accessed)...

..Specifically, the predictive tools can be programmatically accessed using a web interface and can also be downloaded as software packages...

..Several studies suggest that CTL clones can recognize highly diverse peptides, some sharing no obvious sequence identity. The emerging realization in the field is that T cell receptors (TcR) recognize multiple distinct ligands...

..Simulation systems and mathematical modeling are also now beginning to reach a level where these methods will be able to answer more complex immunological questions...

..This wide usage has led to the confusion of defining which of the many methods to use for what problems. In this chapter, an overview is given focusing on the suite of tools developed at the Technical University of Denmark...

..This variation contributes to the observed significant lower likelihood of cancer-specific peptides to be predicted epitopes compared to peptides found in normal tissue...

..As a solution to this challenge, we have implemented a method that predicts the relative surface accessibility of an amino acid and simultaneously predicts the reliability for each prediction, in the form of a Z-score...

..Furthermore, our data suggest a possible role for in silico based miHA predictions in donor selection as well as in selecting candidate miHAs for further evaluation in in vitro and in vivo experiments...

..Chimpanzees control HIV-1 viral replication and develop a chronic infection without progressing to AIDS. A similar course of disease is observed in human long-term non-progressors...

..The updated version of DiscoTope is available at www.cbs.dtu.dk/services/DiscoTope-2.0...

..Here, we will go through some of the history of sequence-based predictions of helper as well as cytotoxic T cell epitopes. We will focus on some of the most accurate methods and their basic background...

..Interpretation of such large peptide datasets, however, is a complex task, especially when the data contain multiple receptor binding motifs, and/or the motifs are found at different locations within distinct peptides...

..Our results, in combination with previously findings, give a detailed picture of the B-cell epitope that may be used in development of improved B-cell prediction methods...

..Predictions by the DiscoTope method can guide experimental epitope mapping in both rational vaccine design and development of diagnostic tools, and may lead to more efficient epitope identification...

..Bioinformatics-based methods are therefore strongly needed to mine the fast growing number of genome sequences and assess in a rapid and reliable way the pathogenicity of novel bacteria...

..To exploit this new potential, a coordinated international effort to analyze the precious source of information represented by rare patients, such as the current victims of bird flu, would be essential...

..Our results have important implications for the validation of potent CTL responses and show that the goal for a vaccine candidate in inducing broadly reactive CTL immune responses is attainable...

..An online version 1.0 of JointML is available at http://www.cbs.dtu.dk/services/VDJsolver...

..New functionalities have been added to most of the previously implemented tools, and a total of eight new tools were added, including two B-cell epitope prediction tools, four T-cell epitope prediction tools and two analysis tools...

..We also discuss the biological relevance of our results, in particular in the context of membrane domains and rafts...

..Thus, it is important to quote the applied dose calculation algorithm when reporting estimates of NTCP parameters in order to ensure correct use of the models...