Related papers: Quantifying selection in immune receptor repertoir…
Chronic infections of the human immunodeficiency virus (HIV) create a very complex co-evolutionary process, where the virus tries to escape the continuously adapting host immune system. Quantitative details of this process are largely…
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…
The adaptive immune system responds to pathogens by selecting clones of cells with specific receptors. While clonal selection in response to particular antigens has been studied in detail, it is unknown how a lifetime of exposures to many…
The emerging field of high-throughput compartmentalized in vitro evolution is a promising new approach to protein engineering. In these experiments, libraries of mutant genotypes are randomly distributed and expressed in microscopic…
In large populations, multiple beneficial mutations may be simultaneously spreading. In asexual populations, these mutations must either arise on the same background or compete against each other. In sexual populations, recombination can…
We study the prediction of T-cell response for specific given peptides, which could, among other applications, be a crucial step towards the development of personalized cancer vaccines. It is a challenging task due to limited, heterogeneous…
The Reduction Principle states that, near a stable equilibrium under fixed viability selection, a selectively neutral modifier allele that reduces recombination rate among selected loci is favored, whereas one that increases recombination…
Genomics biobanks are information treasure troves with thousands of phenotypes (e.g., diseases, traits) and millions of single nucleotide polymorphisms (SNPs). The development of methodologies that provide reproducible discoveries is…
In a co-evolutionary context, the survive probability of individual elements of a system depends on their relation with their neighbors. The natural selection process depends on the whole population, which is determined by local events…
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…
Recognition of pathogens relies on families of proteins showing great diversity. Here we construct maximum entropy models of the sequence repertoire, building on recent experiments that provide a nearly exhaustive sampling of the IgM…
Recent advancements in immune sequencing and experimental techniques are generating extensive T cell receptor (TCR) repertoire data, enabling the development of models to predict TCR binding specificity. Despite the computational challenges…
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…
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…
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…
Cells often have tens of thousands of receptors, even though only a few activated receptors can trigger full cellular responses. Reasons for the overabundance of receptors remain unclear. We suggest that, in certain conditions, the large…
Modeling biological networks serves as both a major goal and an effective tool of systems biology in studying mechanisms that orchestrate the activities of gene products in cells. Biological networks are context specific and dynamic in…
In sexual populations, selection operates neither on the whole genome, which is repeatedly taken apart and reassembled by recombination, nor on individual alleles that are tightly linked to the chromosomal neighborhood. The resulting…
Recent advances in immunomics have shown that T-cell receptor (TCR) signatures can accurately predict active or recent infection by leveraging the high specificity of TCR binding to disease antigens. However, the extreme diversity of the…
Weak purifying selection, acting on many linked mutations, may play a major role in shaping patterns of molecular evolution in natural populations. Yet efforts to infer these effects from DNA sequence data are limited by our incomplete…