PMID- 30556813 OWN - NLM STAT- Publisher LR - 20240227 IS - 1546-1696 (Electronic) IS - 1087-0156 (Linking) DP - 2018 Dec 17 TI - Deep learning using tumor HLA peptide mass spectrometry datasets improves neoantigen identification. LID - 10.1038/nbt.4313 [doi] AB - Neoantigens, which are expressed on tumor cells, are one of the main targets of an effective antitumor T-cell response. Cancer immunotherapies to target neoantigens are of growing interest and are in early human trials, but methods to identify neoantigens either require invasive or difficult-to-obtain clinical specimens, require the screening of hundreds to thousands of synthetic peptides or tandem minigenes, or are only relevant to specific human leukocyte antigen (HLA) alleles. We apply deep learning to a large (N = 74 patients) HLA peptide and genomic dataset from various human tumors to create a computational model of antigen presentation for neoantigen prediction. We show that our model, named EDGE, increases the positive predictive value of HLA antigen prediction by up to ninefold. We apply EDGE to enable identification of neoantigens and neoantigen-reactive T cells using routine clinical specimens and small numbers of synthetic peptides for most common HLA alleles. EDGE could enable an improved ability to develop neoantigen-targeted immunotherapies for cancer patients. FAU - Bulik-Sullivan, Brendan AU - Bulik-Sullivan B AD - Gritstone Oncology, Inc., Emeryville, California and Cambridge, Massachusetts, USA. FAU - Busby, Jennifer AU - Busby J AD - Gritstone Oncology, Inc., Emeryville, California and Cambridge, Massachusetts, USA. FAU - Palmer, Christine D AU - Palmer CD AD - Gritstone Oncology, Inc., Emeryville, California and Cambridge, Massachusetts, USA. FAU - Davis, Matthew J AU - Davis MJ AD - Gritstone Oncology, Inc., Emeryville, California and Cambridge, Massachusetts, USA. FAU - Murphy, Tyler AU - Murphy T AD - Gritstone Oncology, Inc., Emeryville, California and Cambridge, Massachusetts, USA. FAU - Clark, Andrew AU - Clark A AD - Gritstone Oncology, Inc., Emeryville, California and Cambridge, Massachusetts, USA. FAU - Busby, Michele AU - Busby M AD - Gritstone Oncology, Inc., Emeryville, California and Cambridge, Massachusetts, USA. FAU - Duke, Fujiko AU - Duke F AD - Gritstone Oncology, Inc., Emeryville, California and Cambridge, Massachusetts, USA. FAU - Yang, Aaron AU - Yang A AD - Gritstone Oncology, Inc., Emeryville, California and Cambridge, Massachusetts, USA. FAU - Young, Lauren AU - Young L AD - Gritstone Oncology, Inc., Emeryville, California and Cambridge, Massachusetts, USA. FAU - Ojo, Noelle C AU - Ojo NC AD - Gritstone Oncology, Inc., Emeryville, California and Cambridge, Massachusetts, USA. FAU - Caldwell, Kamilah AU - Caldwell K AD - Gritstone Oncology, Inc., Emeryville, California and Cambridge, Massachusetts, USA. FAU - Abhyankar, Jesse AU - Abhyankar J AD - Gritstone Oncology, Inc., Emeryville, California and Cambridge, Massachusetts, USA. FAU - Boucher, Thomas AU - Boucher T AD - Gritstone Oncology, Inc., Emeryville, California and Cambridge, Massachusetts, USA. FAU - Hart, Meghan G AU - Hart MG AD - Gritstone Oncology, Inc., Emeryville, California and Cambridge, Massachusetts, USA. FAU - Makarov, Vladimir AU - Makarov V AD - Memorial Sloan Kettering Cancer Center, New York, New York, USA. FAU - Montpreville, Vincent Thomas De AU - Montpreville VT AD - Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France. FAU - Mercier, Olaf AU - Mercier O AD - Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France. FAU - Chan, Timothy A AU - Chan TA AD - Memorial Sloan Kettering Cancer Center, New York, New York, USA. FAU - Scagliotti, Giorgio AU - Scagliotti G AD - University of Turin, Department of Oncology at San Luigi Hospital, Orbassano (Turin), Italy. FAU - Bironzo, Paolo AU - Bironzo P AD - University of Turin, Department of Oncology at San Luigi Hospital, Orbassano (Turin), Italy. FAU - Novello, Silvia AU - Novello S AD - University of Turin, Department of Oncology at San Luigi Hospital, Orbassano (Turin), Italy. FAU - Karachaliou, Niki AU - Karachaliou N AD - Instituto Oncologico Dr. Rosell - Hospital Universitari Quiron Dexeus Location, Barcelona, Spain. FAU - Rosell, Rafael AU - Rosell R AD - Catalan Institute of Oncology, Barcelona, Spain. FAU - Anderson, Ian AU - Anderson I AD - St Joseph Heritage Healthcare, Santa Rosa, California, USA. FAU - Gabrail, Nashat AU - Gabrail N AD - Gabrail Cancer Center, Canton, Ohio, USA. FAU - Hrom, John AU - Hrom J AD - Hattiesburg Clinic/Forrest General Cancer Center, Hattiesburg, Mississippi, USA. FAU - Limvarapuss, Chainarong AU - Limvarapuss C AD - Solano Hematology Oncology, Vallejo, California, USA. FAU - Choquette, Karin AU - Choquette K AD - Virginia Cancer Specialists, Fairfax, Virginia, USA. FAU - Spira, Alexander AU - Spira A AD - Virginia Cancer Specialists, Fairfax, Virginia, USA. FAU - Rousseau, Raphael AU - Rousseau R AD - Gritstone Oncology, Inc., Emeryville, California and Cambridge, Massachusetts, USA. FAU - Voong, Cynthia AU - Voong C AD - Gritstone Oncology, Inc., Emeryville, California and Cambridge, Massachusetts, USA. FAU - Rizvi, Naiyer A AU - Rizvi NA AD - New York Presbyterian/Columbia University Medical Center, New York, New York, USA. FAU - Fadel, Elie AU - Fadel E AD - Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France. FAU - Frattini, Mark AU - Frattini M AD - New York Presbyterian/Columbia University Medical Center, New York, New York, USA. FAU - Jooss, Karin AU - Jooss K AD - Gritstone Oncology, Inc., Emeryville, California and Cambridge, Massachusetts, USA. FAU - Skoberne, Mojca AU - Skoberne M AD - Gritstone Oncology, Inc., Emeryville, California and Cambridge, Massachusetts, USA. FAU - Francis, Joshua AU - Francis J AD - Gritstone Oncology, Inc., Emeryville, California and Cambridge, Massachusetts, USA. FAU - Yelensky, Roman AU - Yelensky R AUID- ORCID: 0000-0002-5356-0111 AD - Gritstone Oncology, Inc., Emeryville, California and Cambridge, Massachusetts, USA. LA - eng PT - Journal Article DEP - 20181217 PL - United States TA - Nat Biotechnol JT - Nature biotechnology JID - 9604648 EDAT- 2018/12/18 06:00 MHDA- 2018/12/18 06:00 CRDT- 2018/12/18 06:00 PHST- 2018/03/16 00:00 [received] PHST- 2018/11/06 00:00 [accepted] PHST- 2018/12/18 06:00 [entrez] PHST- 2018/12/18 06:00 [pubmed] PHST- 2018/12/18 06:00 [medline] AID - nbt.4313 [pii] AID - 10.1038/nbt.4313 [doi] PST - aheadofprint SO - Nat Biotechnol. 2018 Dec 17. doi: 10.1038/nbt.4313.