Automated benchmarking of peptide-MHC class I binding predictions

Bioinformatics. 2015 Jul 1;31(13):2174-81. doi: 10.1093/bioinformatics/btv123. Epub 2015 Feb 25.


Motivation: Numerous in silico methods predicting peptide binding to major histocompatibility complex (MHC) class I molecules have been developed over the last decades. However, the multitude of available prediction tools makes it non-trivial for the end-user to select which tool to use for a given task. To provide a solid basis on which to compare different prediction tools, we here describe a framework for the automated benchmarking of peptide-MHC class I binding prediction tools. The framework runs weekly benchmarks on data that are newly entered into the Immune Epitope Database (IEDB), giving the public access to frequent, up-to-date performance evaluations of all participating tools. To overcome potential selection bias in the data included in the IEDB, a strategy was implemented that suggests a set of peptides for which different prediction methods give divergent predictions as to their binding capability. Upon experimental binding validation, these peptides entered the benchmark study.

Results: The benchmark has run for 15 weeks and includes evaluation of 44 datasets covering 17 MHC alleles and more than 4000 peptide-MHC binding measurements. Inspection of the results allows the end-user to make educated selections between participating tools. Of the four participating servers, NetMHCpan performed the best, followed by ANN, SMM and finally ARB.

Availability and implementation: Up-to-date performance evaluations of each server can be found online at All prediction tool developers are invited to participate in the benchmark. Sign-up instructions are available at

Contact: or

Supplementary information: Supplementary data are available at Bioinformatics online.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Automation
  • Benchmarking*
  • Computer Simulation
  • Databases, Factual
  • Epitopes / immunology*
  • Histocompatibility Antigens Class I / chemistry
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Peptide Fragments / chemistry
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism*
  • Protein Binding
  • Software


  • Epitopes
  • Histocompatibility Antigens Class I
  • Peptide Fragments