PMID- 31611695 OWN - NLM STAT- MEDLINE DCOM- 20200124 LR - 20240214 IS - 1546-1696 (Electronic) IS - 1087-0156 (Print) IS - 1087-0156 (Linking) VI - 37 IP - 11 DP - 2019 Nov TI - Predicting HLA class II antigen presentation through integrated deep learning. PG - 1332-1343 LID - 10.1038/s41587-019-0280-2 [doi] AB - Accurate prediction of antigen presentation by human leukocyte antigen (HLA) class II molecules would be valuable for vaccine development and cancer immunotherapies. Current computational methods trained on in vitro binding data are limited by insufficient training data and algorithmic constraints. Here we describe MARIA (major histocompatibility complex analysis with recurrent integrated architecture; https://maria.stanford.edu/ ), a multimodal recurrent neural network for predicting the likelihood of antigen presentation from a gene of interest in the context of specific HLA class II alleles. In addition to in vitro binding measurements, MARIA is trained on peptide HLA ligand sequences identified by mass spectrometry, expression levels of antigen genes and protease cleavage signatures. Because it leverages these diverse training data and our improved machine learning framework, MARIA (area under the curve = 0.89-0.92) outperformed existing methods in validation datasets. Across independent cancer neoantigen studies, peptides with high MARIA scores are more likely to elicit strong CD4(+) T cell responses. MARIA allows identification of immunogenic epitopes in diverse cancers and autoimmune disease. FAU - Chen, Binbin AU - Chen B AD - Department of Genetics, Stanford University, Stanford, CA, USA. AD - Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, Stanford, CA, USA. FAU - Khodadoust, Michael S AU - Khodadoust MS AD - Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, Stanford, CA, USA. FAU - Olsson, Niclas AU - Olsson N AUID- ORCID: 0000-0002-9746-0542 AD - Department of Chemical and Systems Biology, Stanford University, Stanford, CA, USA. FAU - Wagar, Lisa E AU - Wagar LE AD - Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA. FAU - Fast, Ethan AU - Fast E AD - Department of Computer Science, Stanford University, Stanford, CA, USA. AD - Nash, Vaduz, Liechtenstein. FAU - Liu, Chih Long AU - Liu CL AD - Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, Stanford, CA, USA. FAU - Muftuoglu, Yagmur AU - Muftuoglu Y AD - Stanford School of Medicine, Stanford University, Stanford, CA, USA. FAU - Sworder, Brian J AU - Sworder BJ AD - Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, Stanford, CA, USA. FAU - Diehn, Maximilian AU - Diehn M AUID- ORCID: 0000-0003-2032-0581 AD - Stanford Cancer Institute, Stanford University, Stanford, CA, USA. AD - Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA. AD - Stem Cell Biology & Regenerative Medicine, Stanford University, Stanford, CA, USA. FAU - Levy, Ronald AU - Levy R AD - Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, Stanford, CA, USA. FAU - Davis, Mark M AU - Davis MM AUID- ORCID: 0000-0001-6868-657X AD - Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA. AD - Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA. FAU - Elias, Joshua E AU - Elias JE AUID- ORCID: 0000-0002-8063-3259 AD - Department of Chemical and Systems Biology, Stanford University, Stanford, CA, USA. AD - Chan Zuckerberg Biohub, Stanford University, Stanford, CA, USA. FAU - Altman, Russ B AU - Altman RB AD - Department of Genetics, Stanford University, Stanford, CA, USA. AD - Department of Bioengineering, Stanford University, Stanford, CA, USA. FAU - Alizadeh, Ash A AU - Alizadeh AA AUID- ORCID: 0000-0002-5153-5625 AD - Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, Stanford, CA, USA. arasha@stanford.edu. AD - Stanford Cancer Institute, Stanford University, Stanford, CA, USA. arasha@stanford.edu. AD - Stem Cell Biology & Regenerative Medicine, Stanford University, Stanford, CA, USA. arasha@stanford.edu. AD - Center for Cancer Systems Biology, Stanford University, Stanford, CA, USA. arasha@stanford.edu. LA - eng GR - U01 CA194389/CA/NCI NIH HHS/United States GR - R01 GM102365/GM/NIGMS NIH HHS/United States GR - S10 RR027431/RR/NCRR NIH HHS/United States GR - U19 AI057229/AI/NIAID NIH HHS/United States GR - K08 CA207882/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20191014 PL - United States TA - Nat Biotechnol JT - Nature biotechnology JID - 9604648 RN - 0 (Histocompatibility Antigens Class II) RN - 0 (Peptides) SB - IM CIN - Nat Rev Clin Oncol. 2020 Feb;17(2):71-72. PMID: 31836878 MH - Antigen Presentation MH - CD4-Positive T-Lymphocytes/*immunology MH - Computational Biology/*methods MH - Deep Learning MH - Histocompatibility Antigens Class II/chemistry/*genetics MH - Humans MH - K562 Cells MH - Mass Spectrometry MH - Neural Networks, Computer MH - Peptides/metabolism MH - Sequence Analysis, RNA PMC - PMC7075463 MID - NIHMS1552539 COIS- Competing interests A.A.A. declares the following competing interests: stock or other ownership (CiberMed and Forty Seven); honoraria (Janssen Oncology); consulting or advisory roles (Celgene, Roche/Genentech and Gilead Sciences); research funding (Celgene); patents, royalties or other intellectual property (patent filings on immune deconvolution and circulating tumor DNA detection assigned to Stanford University); and travel, accommodations or expenses (Roche and Gilead Sciences). R.B.A. declares the following competing interests: stock or other ownership (Personalis); consulting or advisory role (Pfizer, Youscript, 23andme and WithHealth); patents, royalties or other intellectual property (royalties for patents related to genome sequencing). EDAT- 2019/10/16 06:00 MHDA- 2020/01/25 06:00 PMCR- 2020/05/01 CRDT- 2019/10/16 06:00 PHST- 2019/02/22 00:00 [received] PHST- 2019/09/09 00:00 [accepted] PHST- 2019/10/16 06:00 [pubmed] PHST- 2020/01/25 06:00 [medline] PHST- 2019/10/16 06:00 [entrez] PHST- 2020/05/01 00:00 [pmc-release] AID - 10.1038/s41587-019-0280-2 [pii] AID - 10.1038/s41587-019-0280-2 [doi] PST - ppublish SO - Nat Biotechnol. 2019 Nov;37(11):1332-1343. doi: 10.1038/s41587-019-0280-2. Epub 2019 Oct 14.