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The adaptive immune response relies on T cells that combine phenotypic specialization with diversity of T cell receptors (TCRs) to recognize a wide range of pathogens. TCRs are acquired and selected during T cell maturation in the thymus.…

The T-cell (TCR) repertoire relies on the diversity of receptors composed of two chains, called $\alpha$ and $\beta$, to recognize pathogens. Using results of high throughput sequencing and computational chain-pairing experiments of human…

Genomics · Quantitative Biology 2019-05-14 Thomas Dupic , Quentin Marcou , Aleksandra M. Walczak , Thierry Mora

The ability of the adaptive immune system to respond to arbitrary pathogens stems from the broad diversity of immune cell surface receptors (TCRs). This diversity originates in a stochastic DNA editing process (VDJ recombination) that acts…

The diversity of T-cell receptors recognizing foreign pathogens is generated through a highly stochastic recombination process, making the independent production of the same sequence rare. Yet unrelated individuals do share receptors, which…

The efficient recognition of pathogens by the adaptive immune system relies on the diversity of receptors displayed at the surface of immune cells. T-cell receptor diversity results from an initial random DNA editing process, called VDJ…

Populations and Evolution · Quantitative Biology 2015-04-28 Yuval Elhanati , Anand Murugan , Curtis G. Callan , Thierry Mora , Aleksandra M. Walczak

We quantify the VDJ recombination and somatic hypermutation processes in human B-cells using probabilistic inference methods on high-throughput DNA sequence repertoires of human B-cell receptor heavy chains. Our analysis captures the…

Populations and Evolution · Quantitative Biology 2016-02-10 Yuval Elhanati , Zachary Sethna , Quentin Marcou , Curtis G. Callan , Thierry Mora , Aleksandra M. Walczak

A central question in human immunology is how a patient's repertoire of T cells impacts disease. Here, we introduce a method to infer the causal effects of T cell receptor (TCR) sequences on patient outcomes using observational TCR…

Machine Learning · Statistics 2024-10-21 Eli N. Weinstein , Elizabeth B. Wood , David M. Blei

Despite the extreme diversity of T cell repertoires, many identical T-cell receptor (TCR) sequences are found in a large number of individual mice and humans. These widely-shared sequences, often referred to as `public', have been suggested…

Genomics · Quantitative Biology 2019-01-24 Yuval Elhanati , Zachary Sethna , Curtis G. Callan , Thierry Mora , Aleksandra M. Walczak

Stochastic rearrangement of germline DNA by VDJ recombination is at the origin of immune system diversity. This process is implemented via a series of stochastic molecular events involving gene choices and random nucleotide insertions…

Quantitative Methods · Quantitative Biology 2012-11-12 Anand Murugan , Thierry Mora , Aleksandra M. Walczak , Curtis G. Callan

Diverse T and B cell repertoires play an important role in mounting effective immune responses against a wide range of pathogens and malignant cells. The number of unique T and B cell clones is characterized by T and B cell receptors (TCRs…

Quantitative Methods · Quantitative Biology 2026-05-12 Lucas Böttcher , Sascha Wald , Tom Chou

Subclasses of lymphocytes carry different functional roles to work together to produce an immune response and lasting immunity. Additionally to these functional roles, T and B-cell lymphocytes rely on the diversity of their receptor chains…

Populations and Evolution · Quantitative Biology 2021-04-28 Giulio Isacchini , Aleksandra M Walczak , Thierry Mora , Armita Nourmohammad

The human T cell repertoire is generated by the rearrangement of variable (V), diversity (D) and joining (J) segments on the T cell receptor (TCR) loci. To determine whether the structural ordering of these gene segments on the TCR loci…

Genomics · Quantitative Biology 2019-12-17 Amir A. Toor , Abdullah A. Toor , Masoud H. Manjili

T-cell receptors (TCR) are key proteins of the adaptive immune system, generated randomly in each individual, whose diversity underlies our ability to recognize infections and malignancies. Modeling the distribution of TCR sequences is of…

Quantitative Methods · Quantitative Biology 2020-07-01 Giulio Isacchini , Zachary Sethna , Yuval Elhanati , Armita Nourmohammad , Aleksandra M. Walczak , Thierry Mora

The diverse repertoire of T-cell receptors (TCR) plays a key role in the adaptive immune response to infections. Previous studies show that secondary responses to the yellow fever vaccine - the model for acute infection in humans - are…

Understanding the structure of the human T-cell receptor repertoire is a crucial precondition to understand the ability of the immune system to recognize and respond to antigens. T-cells are often compared via the complementarity…

Molecular Networks · Quantitative Biology 2021-12-14 Paul Richter

Recent advances in immunomics have shown that T-cell receptor (TCR) signatures can accurately predict active or recent infection by leveraging the high specificity of TCR binding to disease antigens. However, the extreme diversity of the…

The diversity of the immune repertoire is initially generated by random rearrangements of the receptor gene during early T and B cell development. Rearrangement scenarios are composed of random events -- choices of gene templates, base pair…

Genomics · Quantitative Biology 2016-06-29 Yuval Elhanati , Quentin Marcou , Thierry Mora , Aleksandra M. Walczak

High-throughput sequencing of B- and T-cell receptors makes it possible to track immune repertoires across time, in different tissues, and in acute and chronic diseases or in healthy individuals. However, quantitative comparison between…

Quantitative Methods · Quantitative Biology 2020-11-20 Maximilian Puelma Touzel , Aleksandra M. Walczak , Thierry Mora

T-cell receptors (TCRs) play a crucial role in the immune system by recognizing and binding to specific antigens presented by infected or cancerous cells. Understanding the sequence patterns of TCRs is essential for developing targeted…

Machine Learning · Computer Science 2024-08-05 Yicheng Lin , Dandan Zhang , Yun Liu

T-cell receptor (TCR) repertoire data contain information about infections that could be used in disease diagnostics and vaccine development, but extracting that information remains a major challenge. Here we developed a statistical…

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