NetMHCcons

NetMHCcons is a computational tool for predicting peptide binding to MHC class I molecules. It is a consensus predictor in the NetMHC family that combines the outputs of multiple individual predictors to improve accuracy over any single method. NetMHCcons integrates predictions from NetMHC, NetMHCpan, and PickPocket to produce a final binding score for each peptide–allele pair.

Inputs to NetMHCcons typically include a peptide sequence (commonly 9 amino acids in length) and a specified MHC class I allele. The tool supports a wide range of alleles, including many human HLA variants and non-human MHC molecules. The output provides a predicted binding affinity, usually reported as an IC50 value in nanomolar units, along with a percentile rank and a binder classification (e.g., strong or weak binder) according to established thresholds.

The consensus approach used by NetMHCcons assigns a combined score by weighting the predictions from its constituent methods. By leveraging the strengths and compensating for the biases of individual predictors, NetMHCcons aims to achieve greater accuracy and better generalization across alleles than any single component method.

Availability and usage: NetMHCcons is available as a web server on the official NetMHC site and as a standalone software package. It is often used within immunoinformatics workflows and is integrated into resources such as the IEDB analysis tools, where researchers perform epitope discovery and vaccine design analyses.

Limitations: Like other in silico predictions, NetMHCcons results are probabilistic and depend on the quality of the underlying data. Predicted binders do not guarantee immune presentation or T cell recognition, and experimental validation remains essential.