Related papers: Learning the heterogeneous hypermutation landscape…
Affinity maturation is crucial for improving the binding affinity of antibodies to antigens. This process is mainly driven by point substitutions caused by somatic hypermutations of the immunoglobulin gene. It also includes deletions and…
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…
How does immune system evolve functional proteins - potent antibodies - in such a short time? We address this question using a microscopic, protein-level, sequence-based model of humoral immune response with explicitly defined interactions…
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…
High throughput immune repertoire sequencing is promising to lead to new statistical diagnostic tools for medicine and biology. Successful implementations of these methods require a correct characterization, analysis and interpretation of…
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…
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…
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…
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…
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…
B cell receptor sequences diversify through mutations introduced by purpose-built cellular machinery. A recent paper has concluded that a "templated mutagenesis" process is a major contributor to somatic hypermutation, and therefore…
The evolution of the adaptive immune system is characterized by changes in the relative abundances of the B- and T-cell clones that make up its repertoires. To fully capture this evolution, we need to describe the complex dynamics of the…
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…
With the advent of high-throughput sequencing technologies, the fields of immunogenomics and adaptive immune receptor repertoire research are facing both opportunities and challenges. Adaptive immune receptor repertoire sequencing…
Probabilistic modeling is fundamental to the statistical analysis of complex data. In addition to forming a coherent description of the data-generating process, probabilistic models enable parameter inference about given data sets. This…
Immune cells learn about their antigenic targets using tactile sense: during recognition, a highly organized yet dynamic motif, named immunological synapse, forms between immune cells and antigen-presenting cells (APCs). Via synapses,…
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…
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…
In the genomic era, the identification of gene signatures associated with disease is of significant interest. Such signatures are often used to predict clinical outcomes in new patients and aid clinical decision-making. However, recent…
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…