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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

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

The diversity of T-cell receptor (TCR) repertoires is achieved by a combination of two intrinsically stochastic steps: random receptor generation by VDJ recombination, and selection based on the recognition of random self-peptides presented…

Populations and Evolution · Quantitative Biology 2021-02-05 Zachary Sethna , Giulio Isacchini , Thomas Dupic , Thierry Mora , Aleksandra M. Walczak , Yuval Elhanati

B-cell repertoires are characterized by a diverse set of receptors of distinct specificities generated through two processes of somatic diversification: V(D)J recombination and somatic hypermutations. B cell clonal families stem from the…

Populations and Evolution · Quantitative Biology 2024-03-19 Natanael Spisak , Gabriel Athènes , Thomas Dupic , Thierry Mora , Aleksandra M. Walczak

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…

We introduce a method for approximating posterior probabilities of phylogenetic trees and reconstructing ancestral sequences under models of sequence evolution with site-dependence, where standard phylogenetic likelihood computations…

Populations and Evolution · Quantitative Biology 2025-12-30 Yongkang Li , Kevin J. Wiehe , Scott C. Schmidler

The antibody repertoire of each individual is continuously updated by the evolutionary process of B cell receptor mutation and selection. It has recently become possible to gain detailed information concerning this process through…

Populations and Evolution · Quantitative Biology 2015-05-11 Connor O. McCoy , Trevor Bedford , Vladimir N. Minin , Philip Bradley , Harlan Robins , Frederick A. Matsen

Fundamental to quantitative characterization of the B cell receptor repertoire is clonal diversity - the number of distinct somatically recombined receptors present in the repertoire and their relative abundances, defining the search space…

Quantitative Methods · Quantitative Biology 2017-08-30 William DeWitt , Paul Lindau , Thomas Snyder , Marissa Vignali , Ryan Emerson , Harlan Robins

Within the germinal center in follicles, B-cells proliferate, mutate and differentiate, while being submitted to a powerful selection~: a micro-evolutionary mechanism at the heart of adaptive immunity. A new foreign pathogen is confronted…

Probability · Mathematics 2016-02-12 Irene Balelli , Vuk Milisic , Gilles Wainrib

To recognize pathogens, B and T lymphocytes are endowed with a wide repertoire of receptors generated stochastically by V(D)J recombination. Measuring and estimating the diversity of these receptors is of great importance for understanding…

Populations and Evolution · Quantitative Biology 2020-11-20 Thierry Mora , Aleksandra Walczak

During chronic infection, HIV-1 engages in a rapid coevolutionary arms race with the host's adaptive immune system. While it is clear that HIV exerts strong selection on the adaptive immune system, the characteristics of the somatic…

Populations and Evolution · Quantitative Biology 2020-07-28 Armita Nourmohammad , Jakub Otwinowski , Marta Łuksza , Thierry Mora , Aleksandra M Walczak

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

The human immune system depends on a highly diverse collection of antibody-making B cells. B cell receptor sequence diversity is generated by a random recombination process called "rearrangement" forming progenitor B cells, then a Darwinian…

Populations and Evolution · Quantitative Biology 2017-02-08 Duncan K. Ralph , Frederick A. Matsen

The human body is able to generate a diverse set of high affinity antibodies, the soluble form of B cell receptors (BCRs), that bind to and neutralize invading pathogens. The natural development of BCRs must be understood in order to design…

Methodology · Statistics 2020-09-09 Amrit Dhar , Duncan K. Ralph , Vladimir N. Minin , Frederick A. Matsen

Somatic hypermutations of immunoglobulin (Ig) genes occuring during affinity maturation drive B-cell receptors' ability to evolve strong binding to their antigenic targets. The landscape of these mutations is highly heterogeneous, with…

Genomics · Quantitative Biology 2021-02-05 Natanael Spisak , Aleksandra M. Walczak , Thierry Mora

Cell functional diversity is a significant determinant on how biological processes unfold. Most accounts of diversity involve a search for sequence or expression differences. Perhaps there are more subtle mechanisms at work. Using the…

Quantitative Methods · Quantitative Biology 2013-11-05 Bradly Alicea

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.…

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

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

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
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