Home LiteratureArticle Details
PMID: 26825632 Published · epublish English Journal Article Research Support, N.I.H., Extramural

pVAC-Seq: A genome-guided in silico approach to identifying tumor neoantigens.

Genome medicine ·Vol. 8 ·No. 1 ·2016-01-29 ·Pages 11

Hundal J, Carreno BM, Petti AA, Linette GP, Griffith OL, Mardis ER, Griffith M

Abstract

Cancer immunotherapy has gained significant momentum from recent clinical successes of checkpoint blockade inhibition. Massively parallel sequence analysis suggests a connection between mutational load and response to this class of therapy. Methods to identify which tumor-specific mutant peptides (neoantigens) can elicit anti-tumor T cell immunity are needed to improve predictions of checkpoint therapy response and to identify targets for vaccines and adoptive T cell therapies. Here, we present a flexible, streamlined computational workflow for identification of personalized Variant Antigens by Cancer Sequencing (pVAC-Seq) that integrates tumor mutation and expression data (DNA- and RNA-Seq). pVAC-Seq is available at https://github.com/griffithlab/pVAC-Seq .

MeSH Terms
Antigens, Neoplasm/genetics Computational Biology/methods Computer Simulation Genome, Human Humans Mutation Neoplasms/genetics,immunology Sequence Analysis, DNA/methods Sequence Analysis, RNA/methods Software
Chemicals
Antigens, Neoplasm
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Hundal Jasreet
McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA. jhundal@genome.wustl.edu.
Carreno Beatriz M
Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA. bcarreno@DOM.wustl.edu.
Petti Allegra A
McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA. apetti@genome.wustl.edu.
Linette Gerald P
Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA. glinette@DOM.wustl.edu.
Griffith Obi L
McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA. ogriffit@genome.wustl.edu. | Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA. ogriffit@genome.wustl.edu. | Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA. ogriffit@genome.wustl.edu. | Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA. ogriffit@genome.wustl.edu.
Mardis Elaine R
McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA. emardis@wustl.edu. | Department of Medicine, Division of Genomics and Bioinformatics, Washington University School of Medicine, St. Louis, MO, USA. emardis@wustl.edu. | Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA. emardis@wustl.edu. | Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA. emardis@wustl.edu. | Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. emardis@wustl.edu.
Griffith Malachi
McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA. mgriffit@genome.wustl.edu. | Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA. mgriffit@genome.wustl.edu. | Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA. mgriffit@genome.wustl.edu.
References (46)
46 references, click to expand
  1. Prediction of CD8+ Epitopes in Leishmania braziliensis Proteins Using EPIBOT: In Silico Search and In Vivo Validation.
    PLoS One. 2015;10(4):e0124786 PMID: 25905908
  2. NetMHC-3.0: accurate web accessible predictions of human, mouse and monkey MHC class I affinities for peptides of length 8-11.
    Nucleic Acids Res. 2008 Jul 1;36(Web Server issue):W509-12 PMID: 18463140
  3. Tumor antigens recognized by T lymphocytes.
    Annu Rev Immunol. 1994;12:337-65 PMID: 8011285
  4. EpiToolKit--a web-based workbench for vaccine design.
    Bioinformatics. 2015 Jul 1;31(13):2211-3 PMID: 25712691
  5. The immune epitope database (IEDB) 3.0.
    Nucleic Acids Res. 2015 Jan;43(Database issue):D405-12 PMID: 25300482
  6. NetMHCpan, a method for quantitative predictions of peptide binding to any HLA-A and -B locus protein of known sequence.
    PLoS One. 2007;2(8):e796 PMID: 17726526
  7. A statistical framework for SNP calling, mutation discovery, association mapping and population genetical parameter estimation from sequencing data.
    Bioinformatics. 2011 Nov 1;27(21):2987-93 PMID: 21903627
  8. Somatically mutated tumor antigens in the quest for a more efficacious patient-oriented immunotherapy of cancer.
    Cancer Immunol Immunother. 2015 Jan;64(1):99-104 PMID: 25164877
  9. An overview of bioinformatics tools for epitope prediction: implications on vaccine development.
    J Biomed Inform. 2015 Feb;53:405-14 PMID: 25464113
  10. VarScan: variant detection in massively parallel sequencing of individual and pooled samples.
    Bioinformatics. 2009 Sep 1;25(17):2283-5 PMID: 19542151
  11. NetMHCpan, a method for MHC class I binding prediction beyond humans.
    Immunogenetics. 2009 Jan;61(1):1-13 PMID: 19002680
  12. TopHat: discovering splice junctions with RNA-Seq.
    Bioinformatics. 2009 May 1;25(9):1105-11 PMID: 19289445
  13. VarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencing.
    Genome Res. 2012 Mar;22(3):568-76 PMID: 22300766
  14. Cancer immunotherapy. A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells.
    Science. 2015 May 15;348(6236):803-8 PMID: 25837513
  15. A hybrid approach for predicting promiscuous MHC class I restricted T cell epitopes.
    J Biosci. 2007 Jan;32(1):31-42 PMID: 17426378
  16. Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration.
    Brief Bioinform. 2013 Mar;14(2):178-92 PMID: 22517427
  17. Derivation of HLA types from shotgun sequence datasets.
    Genome Med. 2012 Dec 10;4(12):95 PMID: 23228053
  18. The Sequence Alignment/Map format and SAMtools.
    Bioinformatics. 2009 Aug 15;25(16):2078-9 PMID: 19505943
  19. The IMGT/HLA database.
    Nucleic Acids Res. 2013 Jan;41(Database issue):D1222-7 PMID: 23080122
  20. Quantitative predictions of peptide binding to any HLA-DR molecule of known sequence: NetMHCIIpan.
    PLoS Comput Biol. 2008;4(7):e1000107 PMID: 18604266
  21. Genomic and bioinformatic profiling of mutational neoepitopes reveals new rules to predict anticancer immunogenicity.
    J Exp Med. 2014 Oct 20;211(11):2231-48 PMID: 25245761
  22. Ensembl 2013.
    Nucleic Acids Res. 2013 Jan;41(Database issue):D48-55 PMID: 23203987
  23. High-throughput epitope discovery reveals frequent recognition of neo-antigens by CD4+ T cells in human melanoma.
    Nat Med. 2015 Jan;21(1):81-5 PMID: 25531942
  24. Mining exomic sequencing data to identify mutated antigens recognized by adoptively transferred tumor-reactive T cells.
    Nat Med. 2013 Jun;19(6):747-52 PMID: 23644516
  25. Systematic identification of personal tumor-specific neoantigens in chronic lymphocytic leukemia.
    Blood. 2014 Jul 17;124(3):453-62 PMID: 24891321
  26. TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions.
    Genome Biol. 2013;14(4):R36 PMID: 23618408
  27. Prediction of epitopes using neural network based methods.
    J Immunol Methods. 2011 Nov 30;374(1-2):26-34 PMID: 21047511
  28. BEDTools: a flexible suite of utilities for comparing genomic features.
    Bioinformatics. 2010 Mar 15;26(6):841-2 PMID: 20110278
  29. SomaticSniper: identification of somatic point mutations in whole genome sequencing data.
    Bioinformatics. 2012 Feb 1;28(3):311-7 PMID: 22155872
  30. ATHLATES: accurate typing of human leukocyte antigen through exome sequencing.
    Nucleic Acids Res. 2013 Aug;41(14):e142 PMID: 23748956
  31. Strelka: accurate somatic small-variant calling from sequenced tumor-normal sample pairs.
    Bioinformatics. 2012 Jul 15;28(14):1811-7 PMID: 22581179
  32. Integrative genomics viewer.
    Nat Biotechnol. 2011 Jan;29(1):24-6 PMID: 21221095
  33. Prediction of MHC class I binding peptides using profile motifs.
    Hum Immunol. 2002 Sep;63(9):701-9 PMID: 12175724
  34. Genome Modeling System: A Knowledge Management Platform for Genomics.
    PLoS Comput Biol. 2015 Jul;11(7):e1004274 PMID: 26158448
  35. Tumor exome analysis reveals neoantigen-specific T-cell reactivity in an ipilimumab-responsive melanoma.
    J Clin Oncol. 2013 Nov 10;31(32):e439-42 PMID: 24043743
  36. Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks.
    Nat Protoc. 2012 Mar;7(3):562-78 PMID: 22383036
  37. Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens.
    Nature. 2014 Nov 27;515(7528):577-81 PMID: 25428507
  38. Cancer exome analysis reveals a T-cell-dependent mechanism of cancer immunoediting.
    Nature. 2012 Feb 16;482(7385):400-4 PMID: 22318521
  39. Targeted assembly of short sequence reads.
    PLoS One. 2011;6(5):e19816 PMID: 21589938
  40. Immune recognition of self in immunity against cancer.
    J Clin Invest. 2004 Aug;114(4):468-71 PMID: 15314682
  41. Fast and accurate short read alignment with Burrows-Wheeler transform.
    Bioinformatics. 2009 Jul 15;25(14):1754-60 PMID: 19451168
  42. Pan-specific MHC class I predictors: a benchmark of HLA class I pan-specific prediction methods.
    Bioinformatics. 2009 Jan 1;25(1):83-9 PMID: 18996943
  43. FLEXBAR-Flexible Barcode and Adapter Processing for Next-Generation Sequencing Platforms.
    Biology (Basel). 2012 Dec 14;1(3):895-905 PMID: 24832523
  44. Deriving the consequences of genomic variants with the Ensembl API and SNP Effect Predictor.
    Bioinformatics. 2010 Aug 15;26(16):2069-70 PMID: 20562413
  45. Reliable prediction of T-cell epitopes using neural networks with novel sequence representations.
    Protein Sci. 2003 May;12(5):1007-17 PMID: 12717023
  46. Exploiting the mutanome for tumor vaccination.
    Cancer Res. 2012 Mar 1;72(5):1081-91 PMID: 22237626
Article Info
Journal
Genome medicine
Abbr.
Genome Med
ISSN
1756-994X
DOI
10.1186/s13073-016-0264-5
Email
jhundal@genome.wustl.edu
bcarreno@dom.wustl.edu
apetti@genome.wustl.edu
glinette@dom.wustl.edu
ogriffit@genome.wustl.edu
emardis@wustl.edu
mgriffit@genome.wustl.edu
Published
2016-01-29
Epub
2016-00-29
Pages
11
Language
English
Region
England
NLM ID
101475844
PMCID
PMC4733280
Subset
IM
Grants
NCI NIH HHS · K22 CA188163 · United States
NHGRI NIH HHS · K99 HG007940 · United States
NCI NIH HHS · R21 CA205794 · United States
NHGRI NIH HHS · K99HG007940 · United States
NCI NIH HHS · K22CA188163 · United States
NHGRI NIH HHS · R00 HG007940 · United States
NHGRI NIH HHS · U54 HG003079 · United States
NCI NIH HHS · R21 CA179695 · United States
External Links
PubMed source DOI: 10.1186/s13073-016-0264-5 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2