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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…

Quantitative Methods · Quantitative Biology 2012-11-12 Anand Murugan , Thierry Mora , Aleksandra M. Walczak , Curtis G. Callan

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…

Methodology · Statistics 2020-09-09 Amrit Dhar , Duncan K. Ralph , Vladimir N. Minin , 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

The efficient recognition of pathogens by the adaptive immune system relies on the diversity of receptors displayed at the surface of immune cells. T-cell receptor diversity results from an initial random DNA editing process, called VDJ…

Populations and Evolution · Quantitative Biology 2015-04-28 Yuval Elhanati , Anand Murugan , Curtis G. Callan , Thierry Mora , Aleksandra M. Walczak

Repertoire-level analysis of T cell receptors offers a biologically grounded signal for disease detection and immune monitoring, yet practical deployment is impeded by label sparsity, cohort heterogeneity, and the computational burden of…

Machine Learning · Computer Science 2026-04-23 Rong Fu , Muge Qi , Yang Li , Yabin Jin , Jiekai Wu , Jiaxuan Lu , Chunlei Meng , Youjin Wang , Zeli Su , Juntao Gao , Li Bao , Qi Zhao , Wei Luo , Simon Fong

In the classical setting, the training of a Hidden Markov Model (HMM) typically relies on a single, sufficiently long observation sequence that can be regarded as representative of the underlying stochastic process. In this context, the…

Signal Processing · Electrical Eng. & Systems 2025-10-31 Margarita Cabrera-Bean , Josep Vidal , Sergio Fernandez-Bertolin , Albert Roso-Llorach , Concepcion Violan

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…

Populations and Evolution · Quantitative Biology 2018-05-01 Branden J. Olson , Frederick A. Matsen

T-cell receptors (TCR) are key proteins of the adaptive immune system, generated randomly in each individual, whose diversity underlies our ability to recognize infections and malignancies. Modeling the distribution of TCR sequences is of…

Quantitative Methods · Quantitative Biology 2020-07-01 Giulio Isacchini , Zachary Sethna , Yuval Elhanati , Armita Nourmohammad , Aleksandra M. Walczak , Thierry Mora

To recognize pathogens, B and T lymphocytes are endowed with a wide repertoire of receptors generated stochastically by V(D)J recombination. Measuring and estimating the diversity of these receptors is of great importance for understanding…

Populations and Evolution · Quantitative Biology 2020-11-20 Thierry Mora , Aleksandra Walczak

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

With a view towards molecular communication systems and molecular multi-agent systems, we propose the Chemical Baum-Welch Algorithm, a novel reaction network scheme that learns parameters for Hidden Markov Models (HMMs). Each reaction in…

Emerging Technologies · Computer Science 2023-06-29 Abhinav Singh , Carsten Wiuf , Abhishek Behera , Manoj Gopalkrishnan

The diversity of T-cell receptor (TCR) repertoires is achieved by a combination of two intrinsically stochastic steps: random receptor generation by VDJ recombination, and selection based on the recognition of random self-peptides presented…

Populations and Evolution · Quantitative Biology 2021-02-05 Zachary Sethna , Giulio Isacchini , Thomas Dupic , Thierry Mora , Aleksandra M. Walczak , Yuval Elhanati

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…

Molecular Networks · Quantitative Biology 2017-09-21 John A. P. Sekar , James R. Faeder

The repertoire of lymphocyte receptors in the adaptive immune system protects organisms from diverse pathogens. A well-adapted repertoire should be tuned to the pathogenic environment to reduce the cost of infections. We develop a general…

Populations and Evolution · Quantitative Biology 2016-02-17 Andreas Mayer , Vijay Balasubramanian , Thierry Mora , Aleksandra M. Walczak

VDJ rearrangement and somatic hypermutation work together to produce antibody-coding B cell receptor (BCR) sequences for a remarkable diversity of antigens. It is now possible to sequence these BCRs in high throughput; analysis of these…

Populations and Evolution · Quantitative Biology 2016-02-17 Duncan K. Ralph , Frederick A. Matsen

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

The ability of the adaptive immune system to respond to arbitrary pathogens stems from the broad diversity of immune cell surface receptors (TCRs). This diversity originates in a stochastic DNA editing process (VDJ recombination) that acts…

The adaptive immune system recognizes antigens via an immense array of antigen-binding antibodies and T-cell receptors, the immune repertoire. The interrogation of immune repertoires is of high relevance for understanding the adaptive…

Quantitative Methods · Quantitative Biology 2018-03-02 Enkelejda Miho , Alexander Yermanos , Cédric R. Weber , Christoph T. Berger , Sai T. Reddy , Victor Greiff

T-cell receptors (TCRs) play a crucial role in the immune system by recognizing and binding to specific antigens presented by infected or cancerous cells. Understanding the sequence patterns of TCRs is essential for developing targeted…

Machine Learning · Computer Science 2024-08-05 Yicheng Lin , Dandan Zhang , Yun Liu

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…

Populations and Evolution · Quantitative Biology 2016-02-10 Yuval Elhanati , Zachary Sethna , Quentin Marcou , Curtis G. Callan , Thierry Mora , Aleksandra M. Walczak
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