RT Journal Article
SR Electronic
T1 Immunosequencing reveals diagnostic signatures of chronic viral infection in T cell memory
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 026567
DO 10.1101/026567
A1 Emerson, Ryan O.
A1 DeWitt, William S.
A1 Vignali, Marissa
A1 Gravley, Jenna
A1 Desmarais, Cindy
A1 Carlson, Christopher S.
A1 Hansen, John A.
A1 Rieder, Mark
A1 Robins, Harlan S.
YR 2015
UL http://biorxiv.org/content/early/2015/09/11/026567.abstract
AB 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.