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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 adaptive immune system constantly remodels its lymphocyte repertoire for better protection against future pathogens. Its ability to improve antigen recognition on the fly relies on somatic mutation and selective expansion of B…

Biological Physics · Physics 2022-09-29 Hongda Jiang , Shenshen Wang

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

Cellular decision-making based on information received from the external environment is frequently initiated by transmembrane receptors. These receptors are known to propagate such information by triggering a series of irreversible,…

Biological Physics · Physics 2026-05-13 Samuel L. Foley , Margaret E. Johnson

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 lymphocytes (T cells) orchestrate adaptive immune responses upon activation. T cell activation requires sufficiently strong binding of T cell receptors (TCRs) on their surface to short peptides (p) derived from foreign proteins, which are…

Biological Physics · Physics 2016-06-22 Andrej Kosmrlj , Arup K. Chakraborty , Mehran Kardar , Eugene I. Shakhnovich

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 adaptive immune system is a natural diagnostic and therapeutic. It recognizes threats earlier than clinical symptoms manifest and neutralizes antigen with exquisite specificity. Recognition specificity and broad reactivity is enabled…

Quantitative Methods · Quantitative Biology 2019-07-26 Alex J. Brown , Igor Snapkov , Rahmad Akbar , Milena Pavlović , Enkelejda Miho , Geir K. Sandve , Victor Greiff

The adaptive immune system recognizes antigens via an immense array of antigen-binding antibodies and T-cell receptors, the immune repertoire. The interrogation of immune repertoires is of high relevance for understanding the adaptive…

Quantitative Methods · Quantitative Biology 2018-03-02 Enkelejda Miho , Alexander Yermanos , Cédric R. Weber , Christoph T. Berger , Sai T. Reddy , Victor Greiff

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

The adaptive immune system relies on diversity of its repertoire of receptors to protect the organism from a great variety of pathogens. Since the initial repertoire is the result of random gene rearrangement, binding of receptors is not…

Cell Behavior · Quantitative Biology 2019-10-30 Alexander Mozeika , Franca Fraternali , Deborah Dunn-Walters , Anthony C. C. Coolen

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

The T cell arm of the adaptive immune system provides the host protection against unknown pathogens by discriminating between host and foreign material. This discriminatory capability is achieved by the creation of a repertoire of cells…

Biological Physics · Physics 2022-01-03 Kevin Ng Chau , Jason T. George , José N. Onuchic , Xingcheng Lin , Herbert Levine

Motivation: High-throughput sequencing of large immune repertoires has enabled the development of methods to predict the probability of generation by V(D)J recombination of T- and B-cell receptors of any specific nucleotide sequence. These…

Genomics · Quantitative Biology 2020-11-20 Zachary Sethna , Yuval Elhanati , Curtis G. Callan , Aleksandra M. Walczak , Thierry Mora

T-cells play a key role in adaptive immunity by mounting specific responses against diverse pathogens. An effective binding between T-cell receptors (TCRs) and pathogen-derived peptides presented on Major Histocompatibility Complexes (MHCs)…

Quantitative Methods · Quantitative Biology 2025-09-05 Gian Marco Visani , Michael N. Pun , Anastasia A. Minervina , Philip Bradley , Paul Thomas , Armita Nourmohammad

In most of the recent immunological literature the differences across antigen receptor populations are examined via non-parametric statistical measures of species overlap and diversity borrowed from ecological studies. While this approach…

Biomolecules · Quantitative Biology 2010-03-05 Grzegorz A. Rempala , Michal Seweryn , Leszek Ignatowicz

The amplification cycle of many replicators (natural or artificial) involves the usage of a host compartment, inside of which the replicator express phenotypic compounds necessary to carry out its genetic replication. For example, viruses…

Populations and Evolution · Quantitative Biology 2019-07-03 Anton S. Zadorin , Yannick Rondelez

The vertebrate immune system is a wonder of modern evolution. Occasionally, however, correlations within the immune system lead to inappropriate recruitment of preexisting T cells against novel viral diseases. We present a random energy…

Biomolecules · Quantitative Biology 2009-11-10 Jeong-Man Park , Michael W. Deem

A cornerstone of the classical view of tolerance is the elimination of self-reactive T cells during negative selection in the thymus. However, high-throughput T-cell receptor sequencing data has so far failed to detect substantial…

Populations and Evolution · Quantitative Biology 2023-03-14 Thierry Mora , Aleksandra M. Walczak

The adaptive immune system provides a diverse set of molecules that can mount specific responses against a multitude of pathogens. Memory is a key feature of adaptive immunity, which allows organisms to respond more readily upon…

Populations and Evolution · Quantitative Biology 2021-04-14 Oskar H Schnaack , Armita Nourmohammad