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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…
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…
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…
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…
Computational prediction of the interaction of T cell receptors (TCRs) and their ligands is a grand challenge in immunology. Despite advances in high-throughput assays, specificity-labelled TCR data remains sparse. In other domains, the…
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…
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…
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…
Immune repertoires rely on diversity of T-cell and B-cell receptors to protect us against foreign threats. The ability to recognize a wide variety of pathogens is linked to the number of different clonotypes expressed by an individual. Out…
The immunological synapse is a patterned collection of different types of receptors and ligands that forms in the intercellular junction between T Cells and antigen presenting cells (APCs) during recognition. The synapse is implicated in…
Most statistical classifiers are designed to find patterns in data where numbers fit into rows and columns, like in a spreadsheet, but many kinds of data do not conform to this structure. To uncover patterns in non-conforming data, we…
The immune response to an acute primary infection is a coupled process of antigen proliferation, molecular recognition by naive B cells, and their subsequent proliferation and antibody shedding. This process contains a fundamental problem:…
Cells process external and internal signals through chemical interactions. Cells that constitute the immune system (e.g., antigen presenting cell, T-cell, B-cell, mast cell) can have different functions (e.g., adaptive memory, inflammatory…
One's present repertoire of antibodies encodes the history of one's past immunological experience. Can the present autoantibody repertoire be consulted to predict resistance or susceptibility to the future development of an autoimmune…
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…
Protein language models (PLMs) learn contextual representations from protein sequences and are profoundly impacting various scientific disciplines spanning protein design, drug discovery, and structural predictions. One particular research…
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…
The biophysical interactions between the T cell receptor (TCR) and its ligands determine the specificity of the cellular immune response. However, the immense diversity of receptors and ligands has made it challenging to discover…
Artificial intelligence (AI) is accelerating progress in modeling T and B cell receptors by enabling predictive and generative frameworks grounded in sequence data and immune context. This chapter surveys recent advances in the use of…
Antimicrobial resistance is an important public health concern that has implications in the practice of medicine worldwide. Accurately predicting resistance phenotypes from genome sequences shows great promise in promoting better use of…