• The ESUR PI-RADS scoring system was evaluated using multiparametric 3.0-T MRI. • To investigate suspicious findings, transperineal MR/TRUS fusion-guided biopsy was used. • PI-RADS can guide biopsy locations and improve detection of clinically significant cancer. • Biopsy procedures can be optimised, reducing unnecessary negative biopsies for patients. • The PI-RADS scoring system may contribute to more effective prostate MRI.
Knowing whether a protein can be processed and the resulting peptides presented by major histocompatibility complex (MHC) is highly important for immunotherapy design. MHC ligands can be predicted by in silico peptide-MHC class-I binding prediction algorithms. However, prediction performance differs considerably, 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-to 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 was 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 (A ROC). No algorithm outperformed others, but different algorithms predicted best for particular HLA types and peptide lengths. The 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 prediction algorithms available online, we developed MHCcombine, a web application that allows simultaneous querying and output combination of up to 13 prediction algorithms. Taken together, we provide here an evaluation of peptide-MHC class-I binding prediction tools and recommendations to increase prediction sensitivity to extend the number of potential epitopes applicable as targets for immunotherapy.
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