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PMID: 25143287 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

OptiType: precision HLA typing from next-generation sequencing data.

Bioinformatics (Oxford, England) ·Vol. 30 ·No. 23 ·2014-12-01 ·Pages 3310-6

Szolek A, Schubert B, Mohr C, Sturm M, Feldhahn M, Kohlbacher O

Abstract

The human leukocyte antigen (HLA) gene cluster plays a crucial role in adaptive immunity and is thus relevant in many biomedical applications. While next-generation sequencing data are often available for a patient, deducing the HLA genotype is difficult because of substantial sequence similarity within the cluster and exceptionally high variability of the loci. Established approaches, therefore, rely on specific HLA enrichment and sequencing techniques, coming at an additional cost and extra turnaround time. We present OptiType, a novel HLA genotyping algorithm based on integer linear programming, capable of producing accurate predictions from NGS data not specifically enriched for the HLA cluster. We also present a comprehensive benchmark dataset consisting of RNA, exome and whole-genome sequencing data. OptiType significantly outperformed previously published in silico approaches with an overall accuracy of 97% enabling its use in a broad range of applications.

MeSH Terms
Algorithms Exome Genotyping Techniques HLA Antigens/genetics High-Throughput Nucleotide Sequencing/methods Histocompatibility Testing/methods Humans Introns Sequence Analysis, DNA/methods
Chemicals
HLA Antigens
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Szolek András
Applied Bioinformatics, Center for Bioinformatics, Quantitative Biology Center, and Department of Computer Science, University of Tübingen, Institute of Medical Genetics and Applied Genomics, University of Tübingen, and CeGaT GmbH, 72076 Tübingen, Germany.
Schubert Benjamin
Applied Bioinformatics, Center for Bioinformatics, Quantitative Biology Center, and Department of Computer Science, University of Tübingen, Institute of Medical Genetics and Applied Genomics, University of Tübingen, and CeGaT GmbH, 72076 Tübingen, Germany Applied Bioinformatics, Center for Bioinformatics, Quantitative Biology Center, and Department of Computer Science, University of Tübingen, Institute of Medical Genetics and Applied Genomics, University of Tübingen, and CeGaT GmbH, 72076 Tübingen, Germany.
Mohr Christopher
Applied Bioinformatics, Center for Bioinformatics, Quantitative Biology Center, and Department of Computer Science, University of Tübingen, Institute of Medical Genetics and Applied Genomics, University of Tübingen, and CeGaT GmbH, 72076 Tübingen, Germany Applied Bioinformatics, Center for Bioinformatics, Quantitative Biology Center, and Department of Computer Science, University of Tübingen, Institute of Medical Genetics and Applied Genomics, University of Tübingen, and CeGaT GmbH, 72076 Tübingen, Germany.
Sturm Marc
Applied Bioinformatics, Center for Bioinformatics, Quantitative Biology Center, and Department of Computer Science, University of Tübingen, Institute of Medical Genetics and Applied Genomics, University of Tübingen, and CeGaT GmbH, 72076 Tübingen, Germany.
Feldhahn Magdalena
Applied Bioinformatics, Center for Bioinformatics, Quantitative Biology Center, and Department of Computer Science, University of Tübingen, Institute of Medical Genetics and Applied Genomics, University of Tübingen, and CeGaT GmbH, 72076 Tübingen, Germany.
Kohlbacher Oliver
Applied Bioinformatics, Center for Bioinformatics, Quantitative Biology Center, and Department of Computer Science, University of Tübingen, Institute of Medical Genetics and Applied Genomics, University of Tübingen, and CeGaT GmbH, 72076 Tübingen, Germany.
References (31)
31 references, click to expand
  1. HLA compatibility and organ transplant survival. Collaborative Transplant Study.
    Rev Immunogenet. 1999;1(3):334-42 PMID: 11256424
  2. ATHLATES: accurate typing of human leukocyte antigen through exome sequencing.
    Nucleic Acids Res. 2013 Aug;41(14):e142 PMID: 23748956
  3. Rapid high-throughput human leukocyte antigen typing by massively parallel pyrosequencing for high-resolution allele identification.
    Hum Immunol. 2009 Nov;70(11):960-4 PMID: 19706315
  4. High-resolution, high-throughput HLA genotyping by next-generation sequencing.
    Tissue Antigens. 2009 Nov;74(5):393-403 PMID: 19845894
  5. Transcriptome genetics using second generation sequencing in a Caucasian population.
    Nature. 2010 Apr 1;464(7289):773-7 PMID: 20220756
  6. HLA typing from RNA-seq data using hierarchical read weighting [corrected].
    PLoS One. 2013 Jun 28;8(6):e67885 PMID: 23840783
  7. HLA typing from 1000 genomes whole genome and whole exome illumina data.
    PLoS One. 2013 Nov 06;8(11):e78410 PMID: 24223151
  8. High throughput HLA genotyping using 454 sequencing and the Fluidigm Access Array™ System for simplified amplicon library preparation.
    Tissue Antigens. 2013 Mar;81(3):141-9 PMID: 23398507
  9. HLA complex genes in type 1 diabetes and other autoimmune diseases. Which genes are involved?
    Trends Genet. 2001 Feb;17(2):93-100 PMID: 11173119
  10. The European Nucleotide Archive.
    Nucleic Acids Res. 2011 Jan;39(Database issue):D28-31 PMID: 20972220
  11. SeqAn an efficient, generic C++ library for sequence analysis.
    BMC Bioinformatics. 2008 Jan 09;9:11 PMID: 18184432
  12. Super high resolution for single molecule-sequence-based typing of classical HLA loci at the 8-digit level using next generation sequencers.
    Tissue Antigens. 2012 Oct;80(4):305-16 PMID: 22861646
  13. The genetic basis for interindividual immune response variation to measles vaccine: new understanding and new vaccine approaches.
    Expert Rev Vaccines. 2013 Jan;12(1):57-70 PMID: 23256739
  14. The role of HLA matching in transplantation.
    Immunol Lett. 1991 Jul;29(1-2):55-9 PMID: 1916925
  15. An integrated map of genetic variation from 1,092 human genomes.
    Nature. 2012 Nov 1;491(7422):56-65 PMID: 23128226
  16. Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega.
    Mol Syst Biol. 2011 Oct 11;7:539 PMID: 21988835
  17. HLA typing from RNA-Seq sequence reads.
    Genome Med. 2012 Dec 22;4(12):102 PMID: 23259685
  18. A haplotype map of the human genome.
    Nature. 2005 Oct 27;437(7063):1299-320 PMID: 16255080
  19. Rapid, scalable and highly automated HLA genotyping using next-generation sequencing: a transition from research to diagnostics.
    BMC Genomics. 2013 Apr 04;14:221 PMID: 23557197
  20. A novel single cDNA amplicon pyrosequencing method for high-throughput, cost-effective sequence-based HLA class I genotyping.
    Hum Immunol. 2010 Oct;71(10):1011-7 PMID: 20650293
  21. Next-generation sequencing for HLA typing of class I loci.
    BMC Genomics. 2011 Jan 18;12:42 PMID: 21244689
  22. Vaccinomics: current findings, challenges and novel approaches for vaccine development.
    AAPS J. 2011 Sep;13(3):438-44 PMID: 21671143
  23. Fast gapped-read alignment with Bowtie 2.
    Nat Methods. 2012 Mar 04;9(4):357-9 PMID: 22388286
  24. Ultra-high resolution HLA genotyping and allele discovery by highly multiplexed cDNA amplicon pyrosequencing.
    BMC Genomics. 2012 Aug 06;13:378 PMID: 22866951
  25. The IMGT/HLA database.
    Nucleic Acids Res. 2013 Jan;41(Database issue):D1222-7 PMID: 23080122
  26. Derivation of HLA types from shotgun sequence datasets.
    Genome Med. 2012 Dec 10;4(12):95 PMID: 23228053
  27. Database resources of the National Center for Biotechnology Information.
    Nucleic Acids Res. 2013 Jan;41(Database issue):D8-D20 PMID: 23193264
  28. HLA associated genetic predisposition to autoimmune diseases: Genes involved and possible mechanisms.
    Transpl Immunol. 2005 Aug;14(3-4):175-82 PMID: 15982560
  29. The nature of polymorphism of the HLA class I non-coding regions and their contribution to the diversification of HLA.
    Hereditas. 1997;127(1-2):7-9 PMID: 9471425
  30. Allele frequency net: a database and online repository for immune gene frequencies in worldwide populations.
    Nucleic Acids Res. 2011 Jan;39(Database issue):D913-9 PMID: 21062830
  31. RazerS 3: faster, fully sensitive read mapping.
    Bioinformatics. 2012 Oct 15;28(20):2592-9 PMID: 22923295
Article Info
Journal
Bioinformatics (Oxford, England)
Abbr.
Bioinformatics
ISSN
1367-4811
DOI
10.1093/bioinformatics/btu548
Published
2014-12-01
Epub
2014-00-20
Pages
3310-6
Language
English
Region
England
NLM ID
9808944
PMCID
PMC4441069
Subset
IM
External Links
PubMed source DOI: 10.1093/bioinformatics/btu548 PMC Full Text View journal details
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