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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

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

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…

Genomics · Quantitative Biology 2016-06-29 Yuval Elhanati , Quentin Marcou , Thierry Mora , Aleksandra M. Walczak

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 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

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…

Populations and Evolution · Quantitative Biology 2021-01-27 Duncan K. Ralph , Frederick A. Matsen

Rate variation among the sites of a molecular sequence is commonly found in applications of phylogenetic inference. Several approaches exist to account for this feature but they do not usually enable the investigator to pinpoint the sites…

Quantitative Methods · Quantitative Biology 2013-05-23 Elisa Loza-Reyes , Merrilee Hurn , Tony Robinson

Clusters of genes that have evolved by repeated segmental duplication present difficult challenges throughout genomic analysis, from sequence assembly to functional analysis. Improved understanding of these clusters is of utmost importance,…

Machine Learning · Computer Science 2010-01-25 Tomáš Vinař , Broňa Brejová , Giltae Song , Adam Siepel

We develop a latent variable model and an efficient spectral algorithm motivated by the recent emergence of very large data sets of chromatin marks from multiple human cell types. A natural model for chromatin data in one cell type is a…

Machine Learning · Statistics 2015-06-09 Chicheng Zhang , Jimin Song , Kevin C Chen , Kamalika Chaudhuri

Cis-regulatory modules (CRMs) composed of multiple transcription factor binding sites (TFBSs) control gene expression in eukaryotic genomes. Comparative genomic studies have shown that these regulatory elements are more conserved across…

Applications · Statistics 2007-09-14 Qing Zhou , Wing Hung Wong

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…

Populations and Evolution · Quantitative Biology 2023-12-22 Maria Francesca Abbate , Thomas Dupic , Emmanuelle Vigne , Melody A. Shahsavarian , Aleksandra M. Walczak , Thierry Mora

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…

Populations and Evolution · Quantitative Biology 2024-03-19 Natanael Spisak , Gabriel Athènes , Thomas Dupic , Thierry Mora , Aleksandra M. Walczak

When our immune system encounters foreign antigens (i.e., from pathogens), the B cells that produce our antibodies undergo a cyclic process of proliferation, mutation, and selection, improving their ability to bind to the specific antigen.…

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

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

The proliferation of malware variants poses a significant challenges to traditional malware detection approaches, such as signature-based methods, necessitating the development of advanced machine learning techniques. In this research, we…

Machine Learning · Computer Science 2024-12-30 Ritik Mehta , Olha Jureckova , Mark Stamp

Bayesian phylogenetics is vital for understanding evolutionary dynamics, and requires accurate and efficient approximation of posterior distributions over trees. In this work, we develop a variational Bayesian approach for ultrametric…

Machine Learning · Statistics 2026-02-16 Evan Sidrow , Alexandre Bouchard-Côté , Lloyd T. Elliott

The hidden Markov model (HMM) is a generative model that treats sequential data under the assumption that each observation is conditioned on the state of a discrete hidden variable that evolves in time as a Markov chain. In this paper, we…

Artificial Intelligence · Computer Science 2011-09-07 Emanuele Coviello , Antoni B. Chan , Gert R. G. Lanckriet

Phylogenetics uses alignments of molecular sequence data to learn about evolutionary trees. Substitutions in sequences are modelled through a continuous-time Markov process, characterised by an instantaneous rate matrix, which standard…

Populations and Evolution · Quantitative Biology 2020-07-20 Naomi E. Hannaford , Sarah E. Heaps , Tom M. W. Nye , Tom A. Williams , T. Martin Embley

Cancer is a complex disease characterized by uncontrolled cell growth and proliferation. T cell receptors (TCRs) are essential proteins for the adaptive immune system, and their specific recognition of antigens plays a crucial role in the…

Machine Learning · Computer Science 2023-09-07 Zahra Tayebi , Sarwan Ali , Prakash Chourasia , Taslim Murad , Murray Patterson
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