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We are frequently faced with a large collection of antibodies, and want to select those with highest affinity for their cognate antigen. When developing a first-line therapeutic for a novel pathogen, for instance, we might look for such…

Populations and Evolution · Quantitative Biology 2021-01-27 Duncan K. Ralph , Frederick A. Matsen

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

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

One of the key phenomena in the adaptive immune response to infection and immunization is affinity maturation, during which antibody genes are mutated and selected, typically resulting in a substantial increase in binding affinity to the…

Quantitative Methods · Quantitative Biology 2013-03-05 Thomas B. Kepler

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

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

Antibodies are widely used as therapeutics, but their development requires costly affinity maturation, involving iterative mutations to enhance binding affinity.This paper explores a sequence-only scenario for affinity maturation, using…

Machine Learning · Computer Science 2025-02-18 Can Chen , Karla-Luise Herpoldt , Chenchao Zhao , Zichen Wang , Marcus Collins , Shang Shang , Ron Benson

The mammalian adaptive immune system has evolved over millions of years to become an incredibly effective defense against foreign antigens. The adaptive immune system's humoral response creates plasma B cells and memory B cells, each with…

Cell Behavior · Quantitative Biology 2021-06-21 Stephen Lindsly , Maya Gupta , Cooper Stansbury , Indika Rajapakse

In order to target threatening pathogens, the adaptive immune system performs a continuous reorganization of its lymphocyte repertoire. Following an immune challenge, the B cell repertoire can evolve cells of increased specificity for the…

Populations and Evolution · Quantitative Biology 2022-03-23 Victor Chardès , Massimo Vergassola , Aleksandra M. Walczak , Thierry Mora

Next generation sequencing of B cell receptor (BCR) repertoires has become a ubiquitous tool for understanding the antibody-mediated immune response: it is now common to have large volumes of sequence data coding for both the heavy and…

Genomics · Quantitative Biology 2023-01-11 Duncan K. Ralph , Frederick A. Matsen

B cells and the antibodies they produce are vital to health and survival, motivating research on the details of the mutational and evolutionary processes in the germinal centers (GC) from which mature B cells arise. It is known that B cells…

B cells signaling in response to antigen is proportional to antigen affinity, a process known as affinity discrimination. Recent research suggests that B cells can acquire antigen in membrane-bound form on the surface of antigen-presenting…

Cell Behavior · Quantitative Biology 2010-03-09 Philippos K. Tsourkas , Subhadip Raychaudhuri

The clustering of B cell receptor (BCR) molecules and the formation of the protein segregation structure known as the immunological synapse appears to precede antigen (Ag) uptake by B cells. The mature B cell synapse is characterized by a…

Quantitative Methods · Quantitative Biology 2009-11-13 Philippos K. Tsourkas , Nicole Baumgarth , Scott I. Simon , Subhadip Raychaudhuri

Conformal inference is a method that provides prediction sets for machine learning models, operating independently of the underlying distributional assumptions and relying solely on the exchangeability of training and test data. Despite its…

Methodology · Statistics 2025-10-01 Daniela Corbetta , Livio Finos , Ludwig Geistlinger , Davide Risso

B cell receptors (BCRs) play a crucial role in recognizing and fighting foreign antigens. High-throughput sequencing enables in-depth sampling of the BCRs repertoire after immunization. However, only a minor fraction of BCRs actively…

Populations and Evolution · Quantitative Biology 2023-12-22 Maria Francesca Abbate , Thomas Dupic , Emmanuelle Vigne , Melody A. Shahsavarian , Aleksandra M. Walczak , Thierry Mora

Affinity maturation of antibodies during immune responses is achieved by multiple rounds of somatic hypermutation and subsequent preferential selection of those B cells that express B cell receptors with improved binding characteristics for…

Cell Behavior · Quantitative Biology 2007-05-23 Michael Meyer-Hermann , Philip K. Maini , Dagmar Iber

Many events in the vertebrate immune system are influenced by some element of chance. The objective of the present work is to describe affinity maturation of B lymphocytes (in which random events are perhaps the most characteristic), and to…

Molecular Networks · Quantitative Biology 2015-05-05 Tamás Szabados , Gábor Tusnády , László Varga , Tibor Bakács

A central feature of vertebrate immune response is affinity maturation, wherein antibody-producing B cells undergo evolutionary selection in microanatomical structures called germinal centers, which form in secondary lymphoid organs upon…

Populations and Evolution · Quantitative Biology 2024-02-15 Bertrand Ottino-Loffler , Gabriel Victora

The clonal selection principle explains the basic features of an adaptive immune response to a antigenic stimulus. It established the idea that only those cells that recognize the antigens are selected to proliferate and differentiate. This…

Neural and Evolutionary Computing · Computer Science 2018-04-10 Takumi Ichimura , Shin Kamada

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
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