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@ARTICLE{Bonsack:143345,
author = {M. Bonsack$^*$ and S. Hoppe$^*$ and J. Winter and D.
Tichy$^*$ and C. Zeller$^*$ and M. Küpper$^*$ and E. C.
Schitter$^*$ and R. Blatnik$^*$ and A. Riemer$^*$},
title = {{P}erformance evaluation of {MHC} class-{I} binding
prediction tools based on an experimentally validated
{MHC}-peptide binding dataset.},
journal = {Cancer immunology research},
volume = {7},
number = {5},
issn = {2326-6074},
address = {Philadelphia, Pa.},
publisher = {AACR},
reportid = {DKFZ-2019-00935},
pages = {719-736},
year = {2019},
abstract = {The question whether a protein can be processed and
resulting peptides presented by major histocompatibility
complex (MHC) is of high importance for immunotherapy
design. MHC ligands can be predicted by in silico
peptide-MHC class-I binding prediction algorithms. However,
there are considerable differences in prediction
performance, depending on the selected algorithm, MHC
class-I type and peptide length. We evaluated the prediction
performance of 13 algorithms based on binding affinity data
of 8-11-mer peptides derived from the HPV16 E6 and E7
proteins to the most prevalent human leukocyte antigen (HLA)
types. Peptides from high to low predicted binding
likelihood were synthesized and their HLA binding
experimentally verified by in vitro competitive binding
assays. Based on the actual binding capacity of the
peptides, the performance of prediction algorithms was
analyzed by calculating receiver operating characteristics
(ROC) and the area under the curve (AROC). No algorithm
outperformed others, but different algorithms predicted best
for particular HLA types and peptide lengths. Sensitivity,
specificity and accuracy of decision thresholds were
calculated. Commonly used decision thresholds yielded only
$40\%$ sensitivity. To increase sensitivity, optimal
thresholds were calculated, validated and compared. In order
to make maximal use of online available prediction
algorithms, we developed MHCcombine, a web application that
allows simultaneous querying and output combination of up to
13 prediction algorithms. Taken together, we here provide an
evaluation of peptide-MHC class-I binding prediction tools
and recommendations how to increase prediction sensitivity
to extend the number of potential epitopes applicable as
targets for immunotherapy.},
cin = {F130 / C060},
ddc = {610},
cid = {I:(DE-He78)F130-20160331 / I:(DE-He78)C060-20160331},
pnm = {316 - Infections and cancer (POF3-316)},
pid = {G:(DE-HGF)POF3-316},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30902818},
doi = {10.1158/2326-6066.CIR-18-0584},
url = {https://inrepo02.dkfz.de/record/143345},
}