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通过基于模拟的深度学习推断生发中心进化动力学

Inference of germinal center evolutionary dynamics via simulation-based deep learning.

作者信息

Ralph Duncan K, Bakis Athanasios G, Galloway Jared, Vora Ashni A, Araki Tatsuya, Victora Gabriel D, Song Yun S, DeWitt William S, Matsen Frederick A

机构信息

Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

Department of Statistics, University of California, Irvine, CA.

出版信息

ArXiv. 2025 Aug 13:arXiv:2508.09871v1.

PMID:40832049
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12364052/
Abstract

B cells and the antibodies they produce are vital to health and survival, motivating research on the details of the mutational and evolutionary processes in the germinal centers (GCs) from which mature B cells arise. It is known that B cells with higher affinity for their cognate antigen (Ag) will, on average, tend to have more offspring. However the exact form of this relationship between affinity and fecundity, which we call the "affinity-fitness response function", is not known. Here we use deep learning and simulation-based inference to learn this function from a unique experiment that replays a particular combination of GC conditions many times. All code is freely available at https://github.com/matsengrp/gcdyn, while datasets and inference results can be found at https://doi.org/10.5281/zenodo.15022130.

摘要

B细胞及其产生的抗体对健康和生存至关重要,这推动了对生发中心(GCs)中成熟B细胞产生的突变和进化过程细节的研究。众所周知,对其同源抗原(Ag)具有更高亲和力的B细胞,平均而言,往往会有更多的后代。然而,亲和力与繁殖力之间这种关系的确切形式,即我们所称的“亲和力-适应性反应函数”,尚不清楚。在这里,我们使用深度学习和基于模拟的推理,从一个独特的实验中学习这个函数,该实验多次重现了特定的GC条件组合。所有代码可在https://github.com/matsengrp/gcdyn上免费获取,而数据集和推理结果可在https://doi.org/10.5281/zenodo.15022130上找到。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0be6/12364052/6f5e7194e461/nihpp-2508.09871v1-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0be6/12364052/367e7af9985d/nihpp-2508.09871v1-f0001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0be6/12364052/6f5e7194e461/nihpp-2508.09871v1-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0be6/12364052/367e7af9985d/nihpp-2508.09871v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0be6/12364052/4fb4acc94115/nihpp-2508.09871v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0be6/12364052/ad1cfbcde967/nihpp-2508.09871v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0be6/12364052/2d483c5c6465/nihpp-2508.09871v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0be6/12364052/ff15c5697169/nihpp-2508.09871v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0be6/12364052/847b8507c01f/nihpp-2508.09871v1-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0be6/12364052/6f5e7194e461/nihpp-2508.09871v1-f0007.jpg

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本文引用的文献

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Deep Learning and Likelihood Approaches for Viral Phylogeography Converge on the Same Answers Whether the Inference Model Is Right or Wrong.深度学习和似然方法在病毒系统发育地理学上得出的答案相同,而不管推断模型是正确还是错误。
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Syst Biol. 2023 Dec 30;72(6):1262-1279. doi: 10.1093/sysbio/syad044.
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Competition for refueling rather than cyclic reentry initiation evident in germinal centers.生发中心中存在的是竞争加油而非循环再进入起始。
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