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 Ryan O. Emerson A1 William S. DeWitt A1 Marissa Vignali A1 Jenna Gravley A1 Cindy Desmarais A1 Christopher S. Carlson A1 John A. Hansen A1 Mark Rieder A1 Harlan S. Robins YR 2015 UL http://biorxiv.org/content/early/2015/09/10/026567.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.