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Immunosequencing reveals diagnostic signatures of chronic viral infection in T cell memory

Ryan O. Emerson, William S. DeWitt, Marissa Vignali, Jenna Gravley, Cindy Desmarais, Christopher S. Carlson, John A. Hansen, Mark Rieder, Harlan S. Robins
doi: https://doi.org/10.1101/026567
Ryan O. Emerson
1Adaptive Biotechnologies, Seattle, WA, USA
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  • For correspondence: remerson@adaptivebiotech.com
William S. DeWitt
1Adaptive Biotechnologies, Seattle, WA, USA
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Marissa Vignali
1Adaptive Biotechnologies, Seattle, WA, USA
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Jenna Gravley
2Fred Hutchinson Cancer Research Center, Seattle, WA, USA
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Cindy Desmarais
1Adaptive Biotechnologies, Seattle, WA, USA
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Christopher S. Carlson
2Fred Hutchinson Cancer Research Center, Seattle, WA, USA
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John A. Hansen
2Fred Hutchinson Cancer Research Center, Seattle, WA, USA
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Mark Rieder
1Adaptive Biotechnologies, Seattle, WA, USA
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Harlan S. Robins
1Adaptive Biotechnologies, Seattle, WA, USA
2Fred Hutchinson Cancer Research Center, Seattle, WA, USA
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ABSTRACT

B and T cells expand clonally in response to pathogenic infection, and their descendants, which share the same receptor sequence, can persist for years, forming the basis of immunological memory. While most T cell receptor (TCR) sequences are seen very rarely, ‘public’ TCRs are present in many individuals.

Using a combination of high throughput immunosequencing, statistical association of particular TCRs with disease status, and machine learning, we identified of a set of public TCRs that discriminates cytomegalovirus (CMV) infection status with high accuracy. This pathogen-specific diagnostic tool uses a very general assay that relies only on a training cohort coupled with immunosequencing and sophisticated data analysis. Since all memory T cell responses are encoded in the common format of somatic TCR rearrangements, a key advantage of reading T cell memory to predict disease status is that this approach should apply to a wide variety of diseases. The underlying dataset is the largest collection of TCRs ever published, including ∼300 gigabases of sequencing data and ∼85 million unique TCRs across 640 HLA-typed individuals, which constitutes by far the largest such collection ever published. We expect these data to be a valuable public resource for researchers studying the TCR repertoire.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted September 11, 2015.
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Immunosequencing reveals diagnostic signatures of chronic viral infection in T cell memory
Ryan O. Emerson, William S. DeWitt, Marissa Vignali, Jenna Gravley, Cindy Desmarais, Christopher S. Carlson, John A. Hansen, Mark Rieder, Harlan S. Robins
bioRxiv 026567; doi: https://doi.org/10.1101/026567
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Immunosequencing reveals diagnostic signatures of chronic viral infection in T cell memory
Ryan O. Emerson, William S. DeWitt, Marissa Vignali, Jenna Gravley, Cindy Desmarais, Christopher S. Carlson, John A. Hansen, Mark Rieder, Harlan S. Robins
bioRxiv 026567; doi: https://doi.org/10.1101/026567

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