Reducing junction epitope presentation for neoantigens

A method of identifying a cassette sequence for a neoantigen vaccine, comprising:

• obtaining, for a subject, data representing peptide sequences of each of a set of neoantigens, wherein the peptide sequence of each neoantigen comprises at least one alteration that makes it distinct from a corresponding wild-type, parental peptide sequence identified from normal cells of the subject and includes information regarding a plurality of amino acids that make up the peptide sequence and a set of positions of the amino acids in the peptide sequence;
• inputting the data representing peptide sequences of the neoantigens, using a computer processor, into a machine-learned presentation model to generate a set of numerical presentation likelihoods for the set of neoantigens, each presentation likelihood in the set representing the likelihood that a corresponding neoantigen is presented by one or more MHC alleles on the surface of tumor cells of the subject, the machine-learned presentation model comprising:
• a plurality of parameters identified at least based on a training data set comprising:
• a label obtained by mass spectrometry measuring presence of peptides presented by at least one MHC allele in a set of MHC alleles identified as present in each sample in a set of samples;
• for each of the samples, training peptide sequences including information regarding a plurality of amino acids that make up the training peptide sequences and a set of positions of the amino acids in the training peptide sequences;
• and
• identifying, for the subject, a treatment subset of neoantigens from the set of neoantigens, the treatment subset of neoantigens comprising a predetermined number of neoantigens having presentation likelihoods above a predetermined threshold;
• and
• identifying, for the subject, the cassette sequence comprising a sequence of concatenated therapeutic epitopes that each include the peptide sequence of a corresponding neoantigen in the treatment subset of neoantigens, wherein identifying the cassette sequence comprises:
• inputting sequences of one or more junction epitopes that span junctions between one or more adjacent pairs of therapeutic epitopes into the machine-learned presentation model to determine presentation likelihoods of the one or more junction epitopes;
• and
• selecting an ordering of the therapeutic epitopes in the cassette sequence according to presentation likelihoods of the one or more junction epitopes.