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DeepTCR is a deep learning framework for revealing sequence concepts within T-cell repertoires

Author

Listed:
  • John-William Sidhom

    (Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine)

  • H. Benjamin Larman

    (Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine)

  • Drew M. Pardoll

    (Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine)

  • Alexander S. Baras

    (Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine)

Abstract

Deep learning algorithms have been utilized to achieve enhanced performance in pattern-recognition tasks. The ability to learn complex patterns in data has tremendous implications in immunogenomics. T-cell receptor (TCR) sequencing assesses the diversity of the adaptive immune system and allows for modeling its sequence determinants of antigenicity. We present DeepTCR, a suite of unsupervised and supervised deep learning methods able to model highly complex TCR sequencing data by learning a joint representation of a TCR by its CDR3 sequences and V/D/J gene usage. We demonstrate the utility of deep learning to provide an improved ‘featurization’ of the TCR across multiple human and murine datasets, including improved classification of antigen-specific TCRs and extraction of antigen-specific TCRs from noisy single-cell RNA-Seq and T-cell culture-based assays. Our results highlight the flexibility and capacity for deep neural networks to extract meaningful information from complex immunogenomic data for both descriptive and predictive purposes.

Suggested Citation

  • John-William Sidhom & H. Benjamin Larman & Drew M. Pardoll & Alexander S. Baras, 2021. "DeepTCR is a deep learning framework for revealing sequence concepts within T-cell repertoires," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21879-w
    DOI: 10.1038/s41467-021-21879-w
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    Cited by:

    1. Elliot H. Akama-Garren & Theo Broek & Lea Simoni & Carlos Castrillon & Cees E. Poel & Michael C. Carroll, 2021. "Follicular T cells are clonally and transcriptionally distinct in B cell-driven mouse autoimmune disease," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    2. Giancarlo Croce & Sara Bobisse & Dana Léa Moreno & Julien Schmidt & Philippe Guillame & Alexandre Harari & David Gfeller, 2024. "Deep learning predictions of TCR-epitope interactions reveal epitope-specific chains in dual alpha T cells," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    3. Felix Drost & Yang An & Irene Bonafonte-Pardàs & Lisa M. Dratva & Rik G. H. Lindeboom & Muzlifah Haniffa & Sarah A. Teichmann & Fabian Theis & Mohammad Lotfollahi & Benjamin Schubert, 2024. "Multi-modal generative modeling for joint analysis of single-cell T cell receptor and gene expression data," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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