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基于高通量 pooled 竞争测定的相对适合度的贝叶斯推断。

Bayesian inference of relative fitness on high-throughput pooled competition assays.

机构信息

Department of Biology, Stanford University, Stanford, California, United States of America.

NSF-Simons Center for Quantitative Biology, Northwestern University, Chicago, Illinois, United States of America.

出版信息

PLoS Comput Biol. 2024 Mar 15;20(3):e1011937. doi: 10.1371/journal.pcbi.1011937. eCollection 2024 Mar.

Abstract

The tracking of lineage frequencies via DNA barcode sequencing enables the quantification of microbial fitness. However, experimental noise coming from biotic and abiotic sources complicates the computation of a reliable inference. We present a Bayesian pipeline to infer relative microbial fitness from high-throughput lineage tracking assays. Our model accounts for multiple sources of noise and propagates uncertainties throughout all parameters in a systematic way. Furthermore, using modern variational inference methods based on automatic differentiation, we are able to scale the inference to a large number of unique barcodes. We extend this core model to analyze multi-environment assays, replicate experiments, and barcodes linked to genotypes. On simulations, our method recovers known parameters within posterior credible intervals. This work provides a generalizable Bayesian framework to analyze lineage tracking experiments. The accompanying open-source software library enables the adoption of principled statistical methods in experimental evolution.

摘要

通过 DNA 条码测序来追踪谱系频率,可以量化微生物的适应度。然而,来自生物和非生物源的实验噪声使可靠推断的计算变得复杂。我们提出了一个贝叶斯流水线,从高通量谱系追踪实验中推断相对微生物适应度。我们的模型考虑了多种噪声源,并以系统的方式将不确定性传播到所有参数中。此外,使用基于自动微分的现代变分推断方法,我们能够将推断扩展到大量独特的条码上。我们将这个核心模型扩展到分析多环境实验、重复实验以及与基因型相关的条码。在模拟中,我们的方法在后验置信区间内恢复了已知参数。这项工作提供了一个可推广的贝叶斯框架来分析谱系追踪实验。随附的开源软件库使在实验进化中采用有原则的统计方法成为可能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f581/10971673/55b0502e3432/pcbi.1011937.g001.jpg

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