Abstract

Immune repertoires provide a unique fingerprint reflecting the immune history of individuals, with potential applications in precision medicine. However, the question of how personal that information is and how it can be used to identify individuals has not been explored. Here, we show that individuals can be uniquely identified from repertoires of just a few thousands lymphocytes. We present “Immprint,” a classifier using an information-theoretic measure of repertoire similarity to distinguish pairs of repertoire samples coming from the same versus different individuals. Using published T-cell receptor repertoires and statistical modeling, we tested its ability to identify individuals with great accuracy, including identical twins, by computing false positive and false negative rates < 10−6 from samples composed of 10,000 T-cells. We verified through longitudinal datasets that the method is robust to acute infections and that the immune fingerprint is stable for at least three years. These results emphasize the private and personal nature of repertoire data.

Highlights

  • Personalized medicine is a frequent promise of next-generation sequencing

  • Thanks to their potential for personalized medicine and progress of sequencing technologies, these repertoires are routinely sequenced. As a consequence they raise the question of identifiability of samples

  • We estimate the quantity of immune cells needed to associate two samples from the same individual: as little as a finger prick worth of blood can serve as an immune fingerprint that can distinguish even identical twins, without giving away genetic information about non-consenting relatives. We show that this fingerprint is stable through time, and is not erased during infections or vaccinations

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Summary

Introduction

Personalized medicine is a frequent promise of next-generation sequencing. These highthroughput and low-cost sequencing technologies hold the potential of tailored treatment for each individual. Genome sequences cannot be anonymized: a genetic fingerprint is in itself enough to fully identify an individual, with the rare exception of monozygotic twins. The privacy risks brought by these pseudonymized genomes have been highlighted by multiple studies [1,2,3], and the approach is routinely used by law enforcement. Sequencing experiments that focus on a limited number of expressed genes should be less prone to these concerns. As we will show, B- and T-cell receptor (BCR and TCR) genes are an exception to this rule

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