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T1K: efficient and accurate KIR and HLA genotyping with next-generation sequencing data

Li Song, Gali Bai, X. Shirley Liu, Bo Li, Heng Li
doi: https://doi.org/10.1101/2022.10.26.513955
Li Song
1Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts
2Department of Biomedical Informatics, Harvard Medical School, Boston, Massachusetts
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Gali Bai
1Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts
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X. Shirley Liu
1Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts
4Currently at GV20 Therapeutics, Cambridge, Massachusetts
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Bo Li
3Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, Texas
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  • For correspondence: bo.li@utsouthwestern.edu hli@ds.dfci.harvard.edu
Heng Li
1Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts
2Department of Biomedical Informatics, Harvard Medical School, Boston, Massachusetts
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  • For correspondence: bo.li@utsouthwestern.edu hli@ds.dfci.harvard.edu
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Abstract

Killer immunoglobulin-like receptor (KIR) genes and human leukocyte antigen (HLA) genes are highly polymorphic in a population and play important roles in innate and adaptive immunity. We have developed a novel computational method T1K that can efficiently and accurately infer the KIR or HLA alleles from next-generation sequencing data. T1K is flexible and is compatible with various sequencing platforms including RNA-seq and genomic sequencing data. We applied T1K on CD8+ T cell single-cell RNA-seq data, and identified that KIR2DL4 allele expression levels were enriched in tumor-specific CD8+ T cells.

Competing Interest Statement

X.S.L conducted the work while being on the faculty at DFCI, and is currently a board member and CEO of GV20 Therapeutics. H.L. is a consultant of Integrated DNA Technologies and on the Scientific Advisory Boards of Sentieon and Innozeen.

Footnotes

  • Email addresses: Li Song: lsong{at}ds.dfci.harvard.edu, Gali Bai: galib{at}ds.dfci.harvard.edu, X. Shirley Liu: xsliu.res{at}gmail.com, Bo Li: bo.li{at}utsouthwestern.edu, Heng Li: hli{at}ds.dfci.harvard.edu

  • Abbreviations

    MHC
    major histocompatibility complex
    HLA
    human leukocyte antigen
    KIR
    killer immunoglobulin-like receptor
    NK cell
    natural killer cell
    IPD
    Immuno Polymorphism Database
    WES
    whole-exome sequencing
    WGS
    whole-genome sequencing
    SNP
    single nucleotide polymorphism
    HPRC
    human pangenome reference consortium
    1kGP
    1000 Genome Project
    LRC
    leukocyte receptor complex
  • Copyright 
    The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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    Posted October 27, 2022.
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    T1K: efficient and accurate KIR and HLA genotyping with next-generation sequencing data
    Li Song, Gali Bai, X. Shirley Liu, Bo Li, Heng Li
    bioRxiv 2022.10.26.513955; doi: https://doi.org/10.1101/2022.10.26.513955
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    T1K: efficient and accurate KIR and HLA genotyping with next-generation sequencing data
    Li Song, Gali Bai, X. Shirley Liu, Bo Li, Heng Li
    bioRxiv 2022.10.26.513955; doi: https://doi.org/10.1101/2022.10.26.513955

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