Abstract
Diverse repertoires of hypervariable immunoglobulin receptors (TCR and BCR) recognize antigens in the adaptive immune system. The development of immunoglobulin receptor repertoire sequencing methods makes it possible to perform repertoire-wide disease association studies of antigen receptor sequences. We developed a statistical framework for associating receptors to disease from only a small cohort of patients, with no need for a control cohort. Our method successfully identifies previously validated Cytomegalovirus and type one diabetes responsive TCR[Formula: see text] sequences .
Highlights
Our method successfully identifies previously validated Cytomegalovirus and type 1 diabetes responsive receptors
T-cell receptors (TCR) and B-cell receptors (BCR) are hypervariable immunoglobulins that play a key role in recognizing antigens in the vertebrate immune system
TCR and BCR are formed in the stochastic process of V(D)J recombination, creating a diverse sequence repertoire
Summary
Our framework is applicable to analyze the outcome of a generation sequencing experiment probing the immune receptor repertoires of n individuals with a given condition, e.g. CMV or Type 1 diabetes. We denote by Mi the number of unique amino acid TCR sequences in patient i, i = 1, . For a given TCR amino acid sequence σ, we set xi = 1 to indicate that σ is present in patient i’s repertoire, and xi = 0 otherwise. For a given shared sequence σ, we want to know how likely its sharing pattern is under the null hypothesis of convergent recombination, correcting for the donors’ different. In other words, is σ overrepresented in the population of interest? If σ is significantly overrepresented, we want to quantify the size of this effect In other words, is σ overrepresented in the population of interest? If σ is significantly overrepresented, we want to quantify the size of this effect
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