Related papers: Per-sample immunoglobulin germline inference from …
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 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…
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…
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…
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…
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…
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…
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…
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…
The V(D)J recombination forms the immunoglobulin genes by joining the variable (V), diversity (D), and joining (J) germline genes. Since variations in germline genes have been linked to various diseases, personalized immunogenomics aims at…
Immune repertoires provide a unique fingerprint reflecting the immune history of individuals, with potential applications in precision medicine. However, the question of how personal that information is and how it can be used to identify…
Recently, haplo-identical transplantation with multiple HLA mismatches has become a viable option for system cell transplants. Haplotype sharing detection requires imputation of donor and recipient. We show that even in high-resolution…
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…
DNA sequencing to identify genetic variants is becoming increasingly valuable in clinical settings. Assessment of variants in such sequencing data is commonly implemented through Bayesian heuristic algorithms. Machine learning has shown…
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…
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…
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…
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…
Diverse repertoires of hypervariable immunoglobulin receptors (TCR and BCR) recognize antigens in the adaptive immune system. The development of immunoglobulin receptor repertoire sequencing methods makes it possible to perform…
Modern biological techniques enable very dense genetic sampling of unfolding evolutionary histories, and thus frequently sample some genotypes multiple times. This motivates strategies to incorporate genotype abundance information in…