NetMHCpan

Overview

NetMHCpan is a pan-allele MHC class I binding affinity prediction algorithm that estimates the probability of a peptide being presented by a given HLA allele. It accepts as input a set of peptide sequences and a patient’s personal HLA alleles (typically typed by tools such as POLYSOLVER or ATHLATES), and returns predicted IC50 affinity values. Peptides below a defined affinity threshold (commonly 500 nM, with stricter cutoffs of 150 nM or 50 nM also used) are classified as predicted neoepitopes.

Used by

  • Hugo et al. 2016 — anti-PD-1 melanoma study: NetMHCpan v2.8 (MHC class I) and NetMHCIIpan v3.0 (MHC class II) used to predict neoepitope loads in 38 anti-PD-1-treated metastatic melanoma WES samples; HLA typing performed by ATHLATES; neoepitope load (class I 231 vs 156, p=0.41; class II 130 vs 95, p=0.36) trended higher in responders but did not reach significance PMID:26997480.
  • Giannakis et al. 2016 — CRC neoantigen-survival study: NetMHCpan v2.4 applied to 9-mer and 10-mer mutant peptides with personal HLA alleles (typed by POLYSOLVER) at <500 nM affinity cutoff (alternates: 150 nM and 50 nM also tested); neoantigen load correlated with lymphocytic infiltration (Spearman rho=0.29, p=2.6e-11) and independently predicted improved CRC-specific survival (multivariate HR=0.57, 95% CI 0.35–0.93) in 619 CRC cases PMID:27149842.
  • NetMHC v4.0 used for neoantigen prediction from 9-mer sliding windows of 17-mer mutated peptides (rank<2%) in 68 melanoma WES samples; identified neoantigens selectively depleted on nivolumab in responders PMID:29033130

Notes

  • The standard 500 nM affinity cutoff is considered permissive; stricter cutoffs (150 nM, 50 nM) yield stronger but fewer predicted neoantigens.
  • NetMHCpan does not assess peptide processing efficiency (proteasomal cleavage, TAP transport) or actual T-cell recognition — these are known limitations.
  • The tool accepts patient-specific HLA allele inputs, enabling personalized neoantigen prediction.
  • Pan-allele coverage allows use even for rare HLA alleles not covered by allele-specific models.

Sources

  • Nielsen M, Andreatta M (2016) NetMHCpan-3.0; improved induction of MHC binding motifs. Nucleic Acids Research 44:W551–W556.
  • PMID:26997480
  • PMID:27149842

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This page was processed by entity-page-writer on 2026-05-15.