A method for identifying effective tumor neoantigens
A tumor and antigen technology, applied in biochemical equipment and methods, microbial determination/inspection, etc., can solve problems such as difficult immunogenicity, and achieve the effect of shortening in vitro test cycle, low false screening rate, and reducing the number of tests
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1
[0035] Peptides are classified by mutation position:
[0036] (1) Take tumor tissue and normal tissue samples for whole genome or exome sequencing respectively;
[0037] (2) The mutation position of tumor tissue is obtained by comparative calculation;
[0038] (3) Intercept a 25-peptide polypeptide fragment with 12 residues left and right centered on the mutation position (the length can also be appropriately increased or decreased);
[0039] (4) inputting the clipped segment into the MHC binding prediction algorithm, the present embodiment takes NetMHC 4.0 as an example;
[0040] (5) Select the polypeptide containing the mutation position in the output result (the predicted binding force is higher);
[0041] (6) Classify the above-mentioned polypeptides. The classification is based on the type of mutation position, which is divided into anchor site mutation type, non-anchor site MHC contact type and TCR contact type.
[0042] This example takes the human melanoma mutant pr...
Embodiment 2
[0045] In this example, the human melanoma mutant protein TNR is taken as an example. The mutant polypeptide sequence FWLVDLLPST predicted by NetMHC 4.0 (the wild-type polypeptide is FRLVDLLPST, and the second position is mutated from the wild-type arginine (Arg) residue to tryptophan ( Trp) has a good binding ability to human MHC subtype HLA-A*02:01 (NetMHC4.0 predicted result is 45.1nM).
[0046] Generally, polypeptides bind to the HLA-A*02:01 subtype using the second and last positions as anchor sites. Statistics of the tendency of polypeptide residues in the second and last positions of HLA-A*02:01 show that the second position tends to use leucine (Leu), and the last position tends to use valine (Val) and leucine. acid (Leu) and isoleucine (Ile).
[0047] In this example, the mutation position of the mutant polypeptide FWLVDLLPST is the second position. Based on the above classification rules, this polypeptide can be classified as a new polypeptide with anchor site muta...
Embodiment 3
[0050] In this example, the human melanoma mutant protein HAUS3 is taken as an example. The mutant polypeptide sequence ILNAMIAKI predicted by NetMHC 4.0 (the wild-type polypeptide is ILNAMITKI, and the seventh position is mutated from the wild-type threonine (Thr) residue to alanine ( Ala) has a good binding ability to human MHC subtype HLA-A*02:01 (NetMHC4.0 predicted result is 48.1nM).
[0051] When the 9 peptide binds to the HLA-A*02:01 subtype, its third and seventh positions serve as non-anchor site MHC contact sites. In this example, the mutation position of the mutant polypeptide ILNAMIAKI is the seventh position. Based on the above classification rules, this polypeptide can be classified as a novel polypeptide of the non-anchor site MHC contact class. We believe that the new peptides in this example may be immunogenic.
[0052] Further literature data proves (DOI: 10.1038 / nm.3161) that this new polypeptide can activate CD8+ T cells under HLA-A*02:01 positive conditi...
PUM
| Property | Measurement | Unit |
|---|---|---|
| affinity | aaaaa | aaaaa |
Abstract
Description
Claims
Application Information
Login to View More