RT Journal Article
SR Electronic
T1 Accurate neoantigen prediction depends on mutation position relative to patient allele-specific MHC anchor location
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.12.08.416271
DO 10.1101/2020.12.08.416271
A1 Huiming Xia
A1 Joshua F. McMichael
A1 Suangson Supabphol
A1 Megan M. Richters
A1 Anamika Basu
A1 Cody A. Ramirez
A1 Cristina Puig-Saus
A1 Kelsy C. Cotto
A1 Jasreet Hundal
A1 Susanna Kiwala
A1 S. Peter Goedegebuure
A1 Tanner M. Johanns
A1 Gavin P. Dunn
A1 Todd A. Fehniger
A1 Antoni Ribas
A1 Christopher A. Miller
A1 William E. Gillanders
A1 Obi L. Griffith
A1 Malachi Griffith
YR 2020
UL http://biorxiv.org/content/early/2020/12/08/2020.12.08.416271.abstract
AB Neoantigens are novel peptide sequences resulting from somatic mutations in tumors that upon loading onto major histocompatibility complex (MHC) molecules allow recognition by T cells. Accurate neoantigen identification is thus critical for designing cancer vaccines and predicting response to immunotherapies. Neoantigen identification and prioritization relies on correctly predicting whether the presenting peptide sequence can successfully induce an immune response. As the majority of somatic mutations are SNVs, changes between wildtype and mutant peptide are subtle and require cautious interpretation. An important yet potentially underappreciated variable in neoantigen-prediction pipelines is the mutation position within the peptide relative to its anchor positions for the patient’s specific HLA alleles. While a subset of peptide positions is presented to the T-cell receptor for recognition, others are responsible for anchoring to the MHC, making these positional considerations critical for predicting T-cell responses. We computationally predicted high probability anchor positions for different peptide lengths for over 300 common HLA alleles and identified unique anchoring patterns among them. Analysis of 923 tumor samples shows that 7-41% of neoantigen candidates are potentially misclassified and can be rescued using allele-specific knowledge of anchor positions.Competing Interest StatementThe authors have declared no competing interest.