. Author manuscript; available in PMC: 2022 Oct 1.

Published in final edited form as: Nat Rev Drug Discov. 2022 Feb 1;21(4):261–282. doi: 10.1038/s41573-021-00387-y

Table 3. Hypothesis-driven neoantigen features and prediction algorithms. WT: wild-type.

Name	Function	Input	Comment
MHC-I binding	MHC-I binding prediction	Neoantigen candidate sequence, MHC-I alleles	Several tools, e.g. netMHCpan¹¹⁸
MHC-II binding	MHC-II binding prediction	Neoantigen candidate sequence, MHC-II alleles	Several tools e.g. netMHCIIpan²³⁴
MixMHCpred score ^120,235	Prediction of cell surface presentation of MHC-I epitopes	Neoepitope candidate sequence, MHC-I alleles	Trained on eluted ligands
MixMHC2pred score ²³⁶	Prediction of cell surface presentation of MHC-II epitopes	Neoepitope candidate sequence, MHC-II alleles	Trained on eluted ligands
Transcript expression ^23,102	Transcript expression in FPKM, RPKM or TPM	-	Sveral tools, e.g. kallisto¹¹⁴
Clonality ⁹⁰	The fraction of tumour clones in which a neoantigen is present	Number of reads that cover WT and mutated allele	Several tools, e.g. pyclone¹³⁸
Differential Agretopicity Index (DAI)^89,206.	Difference in MHC-I binding affinities between mutated and WT peptide	MHC-I binding affinity of neoepitope candidate and corresponding WT	-
Self-Similarity ¹³²	Sequence similarity between mutated and WT peptide	Neoepitope candidate and corresponding WT sequence	Relevant for neoepitopes with similar MHC binding as WT peptide
Pathogen similarity ⁵⁰	Similarity to known pathogen epitopes	Neoepitope candidate sequence	BLAST search against pathogen-derived epitopes IEDB database
IEDB immunogenicity ²³⁷	Summed up position-weighted enrichment of residues in immunogenic peptide sequences	Neoepitope candidate sequence	-
Neoantigen dissimilarity ¹³³	Dissimilarity of epitope sequence to self-proteome	Neoepitope candidate sequence	BLAST against WT proteome
PHBR-I ¹²⁸	Mutation presentation by multiple patient MHC-I alleles	Best MHC binding score for each MHC-I allele	-
PHBR-II ¹²⁹	Mutation presentation by multiple patient MHC-II alleles	Best MHC binding score for each MHC-II allele	-
Generator rate ²³⁸	Mutation presentation by multiple neoepitopes	MHC-I binding affinities	-
Recognition potential ^50,92	Combinatorial score considering pathogen-similarity and differential MHC binding of mutated and WT epitope	Neoepitope candidate sequence, MHC-I binding affinities	-
Vaxrank ^239,240	Combinatorial score considering the presentation of a mutation by multiple epitopes and mutated transcript expression	Transcript expression of mutation, MHC-I binding affinities of neoepitope candidates related to a mutation	-
Priority score ²⁴¹	Combinatorial score considering MHC binding and expression	MHC-I binding affinity of neoepitope candidate and WT, transcript expression, variant allele frequency	-
Tcell predictor ²⁴²	Random Forest Model considering several epitope features such as expression, hydrophobicity	Gene name, substitution, neoepitope candidate sequence	-
neoag ²⁴³	Gradient Boosting Model considering epitope sequence intrinsic features	Neoepitope candidate sequence, corresponding WT sequence, variant position, MHC-I binding	Trained on a immunogenicity data set from mouse tumour models