Ranking system for immunogenic cancer-specific epitopes
This disclosure relates to systems and methods that identify, predict, and rank immunogenic T-cell epitopes. In particular, this disclosure identifies epitopes that arose from disease-associated mutations, wherein the epitopes are predicted to elicit immune response from T cells. Specifically, this disclosure simultaneously considers peptide-level information, including MHC Class I and II presentation, helper and cytotoxic T cell response and sample-level information, including mutation clonality and MHC allele dosage. In some embodiment, the systems and methods are used for personalized treatment of cancers.
1. A method for selecting at least one immunogenic mutated peptide, comprising:
(a) obtaining a plurality of mutant sequences;
(b) identifying at least one epitope that derived from a disease-associated mutation;
(c) incorporating a plurality of factors associated with the immunogenicity of the at least one epitope, wherein the plurality of factors comprises a first factor that can be used to calculate a peptide-level score and a second factor that can be used to calculate a sample-level score, wherein the second factor for calculating said sample-level score comprises the clonality of the disease-associated mutation;
(d) weighing the plurality of factors;
(e) assigning an immunogenic score to the at least one epitope based on the weights of the plurality of factors;
(f) ranking the at least one epitope; and
(g) selecting at least one immunogenic mutated peptide based on a ranking result in step (f),
wherein the immunogenic mutated peptide comprises the at least one epitope that may elicit T-cell response.
2. The method of claim 1 , wherein 100 or less epitopes are selected.
3. The method of claim 1 , wherein 50 or less epitopes are selected.
4. The method of claim 1 , wherein 30 or less epitopes are selected.
5. The method of claim 1 , wherein 10 or less epitopes are selected.
6. The method of claim 1 , wherein the plurality of factors accounts for the presentation of the at least one epitopes by MHC class I and class II.
7. The method of claim 5 , wherein the binding affinity of the selected at least one epitope with MHC class I has an IC50 values less than 1500 nM.
8. The method of claim 5 , wherein the plurality of factors comprises MHC class I binding stability.
9. The method of claim 5 , wherein the plurality of factors comprises protein abundance, gene expression or a combination thereof.
10. The method of claim 1 , wherein the plurality of factors accounts for the ability for the at least one epitopes to elicit immune response in cytotoxic T cells.
11. The method of claim 8 , wherein the plurality of factors accounts for the ability for the at least one epitopes to elicit immune response in helper T cell.
12. The method of claim 9 , wherein the plurality of factors comprises the similarity of the at least one epitope to self-peptide.
13. The method of claim 9 , wherein the plurality of factors comprises the homology of the at least one epitope to a known antigens.
14. The method of claim 1 , wherein the variant frequency of the mutation is at least 10%.
15. The method of claim 1 , wherein the variant frequency of the mutation is at least 30%.
16. The method of claim 1 , wherein the plurality of factors comprises copy number, tumor purity, or both copy number and tumor purity.
17. The method of claim 1 , wherein one of the plurality of factors is the status of loss of heterozygosity.
18. The method of claim 1 , wherein one of the plurality of factors is allele dosage.
19. The method of claim 1 , wherein the immunogenic score is integrated from a plurality of factors including MHC class I and class II presentation of the at least one epitopes, the ability for the at least one epitopes to elicit immune response in both helper and cytotoxic T cells, and the clonality of the disease-associated mutation.
20. A system for selecting at least one immunogenic mutated peptide, comprising:
a hardware memory storing computer-executable means of:
(a) obtaining a plurality of mutant sequences;
(b) identifying at least one epitope that derived from a disease-associated mutation;
(c) incorporating a plurality of factors associated with the immunogenicity of the at least one epitope, wherein the plurality of factors comprises a first factor that can be used to calculate a peptide-level score and a second factor that can be used to calculate a sample-level score, wherein the second factor for calculating said sample-level score comprises the clonality of the disease-associated mutation;
(d) weighing the plurality of factors;
(e) assigning an immunogenic score to the at least one epitope based on the weights of the plurality of factors;
(f) ranking the at least one epitope; and
(g) selecting at least one immunogenic mutated peptide based on a ranking result in the step (f),
wherein the immunogenic mutated peptide comprises the at least one epitope that may elicit T-cell response.