@article{a28940b680e74fd68b3582456f31a43d,
title = "Accounting for proximal variants improves neoantigen prediction",
abstract = "Recent efforts to design personalized cancer immunotherapies use predicted neoantigens, but most neoantigen prediction strategies do not consider proximal (nearby) variants that alter the peptide sequence and may influence neoantigen binding. We evaluated somatic variants from 430 tumors to understand how proximal somatic and germline alterations change the neoantigenic peptide sequence and also affect neoantigen binding predictions. On average, 241 missense somatic variants were analyzed per sample. Of these somatic variants, 5% had one or more in-phase missense proximal variants. Without incorporating proximal variant correction for major histocompatibility complex class I neoantigen peptides, the overall false discovery rate (incorrect neoantigens predicted) and the false negative rate (strong-binding neoantigens missed) across peptides of lengths 8–11 were estimated as 0.069 (6.9%) and 0.026 (2.6%), respectively.",
author = "Jasreet Hundal and Susanna Kiwala and Feng, {Yang Yang} and Liu, {Connor J.} and Ramaswamy Govindan and Chapman, {William C.} and Ravindra Uppaluri and Swamidass, {S. Joshua} and Griffith, {Obi L.} and Mardis, {Elaine R.} and Malachi Griffith",
note = "Funding Information: We are grateful to the research participants and their families, without whom this study would not be possible. We thank G. Dunn for early access to raw data for the published glioblastoma hypermutator case included in our analysis. We also thank R. Schreiber and B. Carreno for the initial discussions that inspired the study, and for their expertise and guidance during the study. R.G. was supported by the National Institutes of Health (NIH) National Cancer Institute (U01CA231844). S.J.S. was supported by the NIH National Library of Medicine (R01LM012222 and R01LM012482). O.L.G. was supported by the NIH National Cancer Institute (U01CA209936 and U01CA231844). M.G. was supported by the NIH National Human Genome Research Institute (R00HG007940) and the NIH National Cancer Institute (U01CA209936). Publisher Copyright: {\textcopyright} 2018, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2019",
month = jan,
day = "1",
doi = "10.1038/s41588-018-0283-9",
language = "English",
volume = "51",
pages = "175--179",
journal = "Nature Genetics",
issn = "1061-4036",
number = "1",
}