Methods of vaccine design

3:

• The computer-implemented method according to claim 2, wherein simulating the plurality of cancer cells comprises predicting a presence or absence of each identified gene variants of the set of identified gene variants in each cancer cell of the plurality of cancer cells based on a statistical distribution of the set of identified gene variants.

4:

• The computer-implemented method according to claim 3, wherein simulating the plurality of cancer cells comprises estimating an abundance of one or more proteins synthesized in each cancer cell of the plurality of cancer cells based on the gene expression information and on the set of identified gene variants predicted to be present in each cancer cell.

5:

• The computer-implemented method according to claim 4, wherein simulating the plurality of cancer cells comprises estimating an abundance of one or more peptides processed in each cancer cell based on the estimated abundance of one or more proteins synthesised in said cancer cell and on a likelihood of each of the one or more proteins being split into the one or more peptides.

6:

• The computer-implemented method according to claim 5, wherein simulating the plurality of cancer cells comprises simulating a binding of the one or more peptides to HLA molecules to estimate a likelihood of one or more peptide-HLA complexes being present in each cancer cell of the plurality of cancer cells, wherein simulating the binding of the one or more peptides to HLA molecules is based on an abundance of said one or more peptides and on binding affinity indicators for each tuple of candidate neoantigen amino acid sequence and HLA-I allele.

7:

• The computer-implemented method according to claim 6, wherein simulating the plurality of cancer cells comprises predicting the cell surface presentation of each cancer cell of the plurality of cancer cells based on the likelihood of the one or more peptide-HLA complexes being present within each cancer cell of the plurality of cancer cells and on the presentation indicators for each tuple of candidate neoantigen amino acid sequence and HLA-I allele.

8:

• The computer-implemented method according to claim 1, wherein predicting the likelihood of each candidate neoantigen amino acid sequence eliciting the immune response to the plurality of cancer cells comprises estimating a likelihood of a patient's immune system including T cells having receptors which bind with the predicted cell surface presentation of each cancer cell.

9:

• The computer-implemented method according to claim 1, wherein selecting the one or more amino acid sequences of the set of candidate neoantigen amino acid sequences for inclusion in the neoantigen vaccine comprises applying a mathematical optimisation algorithm to minimise a likelihood of the neoantigen vaccine eliciting no immune response to the cancer cells.

11:

• The computer-implemented method according to claim 1, wherein selecting the one or more amino acid sequences for inclusion in the neoantigen vaccine comprises applying a mathematical optimisation algorithm to minimise a likelihood of the neoantigen vaccine eliciting no immune response to the each cancer cell for which a likelihood of no immune response being elicited by the neoantigen vaccine is highest.

13:

• The computer-implemented method according to claim 9, wherein the mathematical optimisation algorithm is an integer linear program.

14:

• The computer-implemented method according to claim 1, wherein the method further comprises assigning a cost to each candidate neoantigen amino acid sequence, and the step of selecting the one or more amino acid sequences for inclusion in the neoantigen vaccine is constrained based on the cost assigned to each candidate neoantigen amino acid sequence, such that the selected one or more amino acid sequences have a total cost below a predetermined threshold budget.

16:

• A system for selecting one or more amino acid sequences for inclusion in a vaccine from a set of candidate neoantigen amino acid sequences, the system comprising at least one processor in communication with at least one memory device, the at least one memory device having stored thereon instructions for causing the at least one processor to perform a method according to claim 1.

17:

• A computer-readable medium having computer executable instructions stored thereon for, when executed by at least one processor, implementing a method according to claim 1.