Bioinformatics (Oxford, England) 2017 01 10() pii 10.1093/bioinformatics/btw771
Somatic DNA recombination, the hallmark of vertebrate adaptive immunity, has the potential to generate a vast diversity of antigen receptor sequences. How this diversity captures antigen specificity remains incompletely understood. In this study we use high throughput sequencing to compare the global changes in T cell receptor β chain complementarity determining region 3 (CDR3β) sequences following immunization with ovalbumin administered with complete Freund’s adjuvant (CFA) or CFA alone.
The CDR3β sequences were deconstructed into short stretches of overlapping contiguous amino acids. The motifs were ranked according to a one-dimensional Bayesian classifier score comparing their frequency in the repertoires of the two immunization classes. The top ranking motifs were selected and used to create feature vectors which were used to train a support vector machine. The support vector machine achieved high classification scores in a leave-one-out validation test reaching : >90% in some cases.
The study describes a novel two-stage classification strategy combining a one-dimensional Bayesian classifier with a support vector machine. Using this approach we demonstrate that the frequency of a small number of linear motifs three amino acids in length can accurately identify a CD4 T cell response to ovalbumin against a background response to the complex mixture of antigens which characterize Complete Freund’s Adjuvant.
AVAILABILITY AND IMPLEMENTATION
The sequence data is available at www.ncbi.nlm.nih.gov/sra/?term¼SRP075893 The Decombinator package is available at github.com/innate2adaptive/Decombinator The R package e1071 is available at the CRAN repository https://cran.r-project.org/web/packages/e1071/index.html CONTACT: firstname.lastname@example.orgSupplementary information: Supplementary data are available at Bioinformatics online.