PMID- 37816353 OWN - NLM STAT- MEDLINE DCOM- 20231117 LR - 20231117 IS - 1097-4180 (Electronic) IS - 1074-7613 (Linking) VI - 56 IP - 11 DP - 2023 Nov 14 TI - Machine learning methods and harmonized datasets improve immunogenic neoantigen prediction. PG - 2650-2663.e6 LID - S1074-7613(23)00406-5 [pii] LID - 10.1016/j.immuni.2023.09.002 [doi] AB - The accurate selection of neoantigens that bind to class I human leukocyte antigen (HLA) and are recognized by autologous T cells is a crucial step in many cancer immunotherapy pipelines. We reprocessed whole-exome sequencing and RNA sequencing (RNA-seq) data from 120 cancer patients from two external large-scale neoantigen immunogenicity screening assays combined with an in-house dataset of 11 patients and identified 46,017 somatic single-nucleotide variant mutations and 1,781,445 neo-peptides, of which 212 mutations and 178 neo-peptides were immunogenic. Beyond features commonly used for neoantigen prioritization, factors such as the location of neo-peptides within protein HLA presentation hotspots, binding promiscuity, and the role of the mutated gene in oncogenicity were predictive for immunogenicity. The classifiers accurately predicted neoantigen immunogenicity across datasets and improved their ranking by up to 30%. Besides insights into machine learning methods for neoantigen ranking, we have provided homogenized datasets valuable for developing and benchmarking companion algorithms for neoantigen-based immunotherapies. CI - Copyright (c) 2023 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Muller, Markus AU - Muller M AD - Ludwig Institute for Cancer Research, University of Lausanne, Agora Center Bugnon 25A, 1005 Lausanne, Switzerland; Department of Oncology, Centre hospitalier universitaire vaudois (CHUV), Rue du Bugnon 46, 1005 Lausanne, Switzerland; Agora Cancer Research Centre, 1011 Lausanne, Switzerland; SIB Swiss Institute of Bioinformatics, Quartier Sorge, Batiment Amphipole, 1015 Lausanne, Switzerland. Electronic address: markus.muller@chuv.ch. FAU - Huber, Florian AU - Huber F AD - Ludwig Institute for Cancer Research, University of Lausanne, Agora Center Bugnon 25A, 1005 Lausanne, Switzerland; Department of Oncology, Centre hospitalier universitaire vaudois (CHUV), Rue du Bugnon 46, 1005 Lausanne, Switzerland; Agora Cancer Research Centre, 1011 Lausanne, Switzerland. FAU - Arnaud, Marion AU - Arnaud M AD - Ludwig Institute for Cancer Research, University of Lausanne, Agora Center Bugnon 25A, 1005 Lausanne, Switzerland; Department of Oncology, Centre hospitalier universitaire vaudois (CHUV), Rue du Bugnon 46, 1005 Lausanne, Switzerland; Agora Cancer Research Centre, 1011 Lausanne, Switzerland. FAU - Kraemer, Anne I AU - Kraemer AI AD - Ludwig Institute for Cancer Research, University of Lausanne, Agora Center Bugnon 25A, 1005 Lausanne, Switzerland; Department of Oncology, Centre hospitalier universitaire vaudois (CHUV), Rue du Bugnon 46, 1005 Lausanne, Switzerland; Agora Cancer Research Centre, 1011 Lausanne, Switzerland. FAU - Altimiras, Emma Ricart AU - Altimiras ER AD - Ludwig Institute for Cancer Research, University of Lausanne, Agora Center Bugnon 25A, 1005 Lausanne, Switzerland; Department of Oncology, Centre hospitalier universitaire vaudois (CHUV), Rue du Bugnon 46, 1005 Lausanne, Switzerland; Agora Cancer Research Centre, 1011 Lausanne, Switzerland. FAU - Michaux, Justine AU - Michaux J AD - Ludwig Institute for Cancer Research, University of Lausanne, Agora Center Bugnon 25A, 1005 Lausanne, Switzerland; Department of Oncology, Centre hospitalier universitaire vaudois (CHUV), Rue du Bugnon 46, 1005 Lausanne, Switzerland; Agora Cancer Research Centre, 1011 Lausanne, Switzerland. FAU - Taillandier-Coindard, Marie AU - Taillandier-Coindard M AD - Ludwig Institute for Cancer Research, University of Lausanne, Agora Center Bugnon 25A, 1005 Lausanne, Switzerland; Department of Oncology, Centre hospitalier universitaire vaudois (CHUV), Rue du Bugnon 46, 1005 Lausanne, Switzerland; Agora Cancer Research Centre, 1011 Lausanne, Switzerland. FAU - Chiffelle, Johanna AU - Chiffelle J AD - Ludwig Institute for Cancer Research, University of Lausanne, Agora Center Bugnon 25A, 1005 Lausanne, Switzerland; Department of Oncology, Centre hospitalier universitaire vaudois (CHUV), Rue du Bugnon 46, 1005 Lausanne, Switzerland; Agora Cancer Research Centre, 1011 Lausanne, Switzerland. FAU - Murgues, Baptiste AU - Murgues B AD - Ludwig Institute for Cancer Research, University of Lausanne, Agora Center Bugnon 25A, 1005 Lausanne, Switzerland; Department of Oncology, Centre hospitalier universitaire vaudois (CHUV), Rue du Bugnon 46, 1005 Lausanne, Switzerland; Agora Cancer Research Centre, 1011 Lausanne, Switzerland. FAU - Gehret, Talita AU - Gehret T AD - Ludwig Institute for Cancer Research, University of Lausanne, Agora Center Bugnon 25A, 1005 Lausanne, Switzerland; Department of Oncology, Centre hospitalier universitaire vaudois (CHUV), Rue du Bugnon 46, 1005 Lausanne, Switzerland; Agora Cancer Research Centre, 1011 Lausanne, Switzerland. FAU - Auger, Aymeric AU - Auger A AD - Ludwig Institute for Cancer Research, University of Lausanne, Agora Center Bugnon 25A, 1005 Lausanne, Switzerland; Department of Oncology, Centre hospitalier universitaire vaudois (CHUV), Rue du Bugnon 46, 1005 Lausanne, Switzerland; Agora Cancer Research Centre, 1011 Lausanne, Switzerland. FAU - Stevenson, Brian J AU - Stevenson BJ AD - Agora Cancer Research Centre, 1011 Lausanne, Switzerland; SIB Swiss Institute of Bioinformatics, Quartier Sorge, Batiment Amphipole, 1015 Lausanne, Switzerland. FAU - Coukos, George AU - Coukos G AD - Ludwig Institute for Cancer Research, University of Lausanne, Agora Center Bugnon 25A, 1005 Lausanne, Switzerland; Department of Oncology, Centre hospitalier universitaire vaudois (CHUV), Rue du Bugnon 46, 1005 Lausanne, Switzerland; Agora Cancer Research Centre, 1011 Lausanne, Switzerland; Center of Experimental Therapeutics, Department of Oncology, Centre hospitalier universitaire vaudois (CHUV), Rue du Bugnon 46, 1005 Lausanne, Switzerland. FAU - Harari, Alexandre AU - Harari A AD - Ludwig Institute for Cancer Research, University of Lausanne, Agora Center Bugnon 25A, 1005 Lausanne, Switzerland; Department of Oncology, Centre hospitalier universitaire vaudois (CHUV), Rue du Bugnon 46, 1005 Lausanne, Switzerland; Agora Cancer Research Centre, 1011 Lausanne, Switzerland; Center of Experimental Therapeutics, Department of Oncology, Centre hospitalier universitaire vaudois (CHUV), Rue du Bugnon 46, 1005 Lausanne, Switzerland. FAU - Bassani-Sternberg, Michal AU - Bassani-Sternberg M AD - Ludwig Institute for Cancer Research, University of Lausanne, Agora Center Bugnon 25A, 1005 Lausanne, Switzerland; Department of Oncology, Centre hospitalier universitaire vaudois (CHUV), Rue du Bugnon 46, 1005 Lausanne, Switzerland; Agora Cancer Research Centre, 1011 Lausanne, Switzerland; Center of Experimental Therapeutics, Department of Oncology, Centre hospitalier universitaire vaudois (CHUV), Rue du Bugnon 46, 1005 Lausanne, Switzerland. Electronic address: michal.bassani@chuv.ch. LA - eng PT - Journal Article DEP - 20231009 PL - United States TA - Immunity JT - Immunity JID - 9432918 RN - 0 (Antigens, Neoplasm) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Peptides) SB - IM MH - Humans MH - *Antigens, Neoplasm/genetics MH - *Neoplasms/genetics/therapy MH - Histocompatibility Antigens Class I MH - Machine Learning MH - Peptides MH - Immunotherapy/methods OTO - NOTNLM OT - cancer immunotherapy OT - machine learning OT - neoantigen prioritization OT - personalized cancer vaccine COIS- Declaration of interests The research presented in this paper is associated with the pending patent application PCT/EP2022/082845. The inventors listed on the patent application are M.B.-S., F.H., and M.M. EDAT- 2023/10/11 00:42 MHDA- 2023/11/17 15:25 CRDT- 2023/10/10 18:42 PHST- 2023/03/27 00:00 [received] PHST- 2023/06/26 00:00 [revised] PHST- 2023/09/05 00:00 [accepted] PHST- 2023/11/17 15:25 [medline] PHST- 2023/10/11 00:42 [pubmed] PHST- 2023/10/10 18:42 [entrez] AID - S1074-7613(23)00406-5 [pii] AID - 10.1016/j.immuni.2023.09.002 [doi] PST - ppublish SO - Immunity. 2023 Nov 14;56(11):2650-2663.e6. doi: 10.1016/j.immuni.2023.09.002. Epub 2023 Oct 9.