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The adaptive immune response, largely mediated by B-cell receptors (BCRs), plays a crucial role for effective pathogen neutralization due to its diversity and antigen specificity. Designing BCRs de novo, or from scratch, has been…

Biomolecules · Quantitative Biology 2024-09-11 Desmond Kuan , Amir Barati Farimani

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…

Cell Behavior · Quantitative Biology 2008-05-27 Muyoung Heo , Konstantin B. Zeldovich , Eugene I. Shakhnovich

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

Antibodies offer great potential for the treatment of various diseases. However, the discovery of therapeutic antibodies through traditional wet lab methods is expensive and time-consuming. The use of generative models in designing…

Antibodies are widely used reagents to test for expression of proteins and other antigens. However, they might not always reliably produce results when they do not specifically bind to the target proteins that their providers designed them…

Immune cells learn about their antigenic targets using tactile sense: during recognition, a highly organized yet dynamic motif, named immunological synapse, forms between immune cells and antigen-presenting cells (APCs). Via synapses,…

Biological Physics · Physics 2018-12-12 Miloš Knežević , Shenshen Wang

In recent decades, antibodies have emerged as indispensable therapeutics for combating diseases, particularly viral infections. However, their development has been hindered by limited structural information and labor-intensive engineering…

Biomolecules · Quantitative Biology 2023-09-01 Hongtai Jing , Zhengtao Gao , Sheng Xu , Tao Shen , Zhangzhi Peng , Shwai He , Tao You , Shuang Ye , Wei Lin , Siqi Sun

Current antibody language models are limited by their use of unpaired antibody sequence data and the biases in publicly available antibody sequence datasets, which are skewed toward antibodies against a relatively small number of pathogens.…

Biomolecules · Quantitative Biology 2023-11-08 Sarah M. Burbach , Bryan Briney

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

A pivotal area of research in antibody engineering is to find effective modifications that enhance antibody-antigen binding affinity. Traditional wet-lab experiments assess mutants in a costly and time-consuming manner. Emerging deep…

Quantitative Methods · Quantitative Biology 2025-05-28 Chen Liu , Mingchen Li , Yang Tan , Wenrui Gou , Guisheng Fan , Bingxin Zhou

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

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…

Attention-based models trained on protein sequences have demonstrated incredible success at classification and generation tasks relevant for artificial intelligence-driven protein design. However, we lack a sufficient understanding of how…

Machine Learning · Computer Science 2022-06-29 Erik Nijkamp , Jeffrey Ruffolo , Eli N. Weinstein , Nikhil Naik , Ali Madani

Therapeutic antibody development has become an increasingly popular approach for drug development. To date, antibody therapeutics are largely developed using large scale experimental screens of antibody libraries containing hundreds of…

Quantitative Methods · Quantitative Biology 2022-10-07 Lin Li , Esther Gupta , John Spaeth , Leslie Shing , Tristan Bepler , Rajmonda Sulo Caceres

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.…

Language models can achieve high accuracy on natural language tasks such as NLI, but performance suffers on manually created adversarial examples. We investigate the performance of a language model trained on the Stanford Natural Language…

Computation and Language · Computer Science 2024-10-31 Chris Achard

The toxins associated with infectious diseases are potential targets for inhibitors which have the potential for prophylactic or therapeutic use. Many antibodies have been generated for this purpose, and the objective of this study was to…

Quantitative Methods · Quantitative Biology 2015-03-19 Alex Skvortsov , Peter Gray

Immune repertoire classification, a typical multiple instance learning (MIL) problem, is a frontier research topic in computational biology that makes transformative contributions to new vaccines and immune therapies. However, the…

Machine Learning · Computer Science 2023-08-01 Mingcai Chen , Yu Zhao , Zhonghuang Wang , Bing He , Jianhua Yao

An adaptive agent predicting the future state of an environment must weigh trust in new observations against prior experiences. In this light, we propose a view of the adaptive immune system as a dynamic Bayesian machinery that updates its…

Populations and Evolution · Quantitative Biology 2019-05-14 Andreas Mayer , Vijay Balasubramanian , Aleksandra M. Walczak , Thierry Mora

We propose an alternate approach to quantifying how well language models learn natural language: we ask how well they match the statistical tendencies of natural language. To answer this question, we analyze whether text generated from…

Computation and Language · Computer Science 2021-08-31 Clara Meister , Ryan Cotterell