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利用大规模平行报告基因检测和机器学习解码生物学。

Decoding biology with massively parallel reporter assays and machine learning.

机构信息

Paul G. Allen School of Computer Science and Engineering, University of Washington, Seattle, Washington 98195, USA.

Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, Irvine, California 92697, USA;

出版信息

Genes Dev. 2024 Oct 16;38(17-20):843-865. doi: 10.1101/gad.351800.124.

Abstract

Massively parallel reporter assays (MPRAs) are powerful tools for quantifying the impacts of sequence variation on gene expression. Reading out molecular phenotypes with sequencing enables interrogating the impact of sequence variation beyond genome scale. Machine learning models integrate and codify information learned from MPRAs and enable generalization by predicting sequences outside the training data set. Models can provide a quantitative understanding of -regulatory codes controlling gene expression, enable variant stratification, and guide the design of synthetic regulatory elements for applications from synthetic biology to mRNA and gene therapy. This review focuses on -regulatory MPRAs, particularly those that interrogate cotranscriptional and post-transcriptional processes: alternative splicing, cleavage and polyadenylation, translation, and mRNA decay.

摘要

大规模平行报告分析(MPRAs)是一种强大的工具,可用于量化序列变异对基因表达的影响。通过测序读出分子表型,可以研究超出基因组规模的序列变异的影响。机器学习模型整合并编码从 MPRAs 中学习到的信息,并通过预测训练数据集之外的序列来实现泛化。模型可以提供对调控基因表达的 - 调控代码的定量理解,实现变体分层,并指导合成调控元件的设计,应用范围从合成生物学到 mRNA 和基因治疗。本文综述了 - 调控 MPRAs,特别是那些检测共转录和转录后过程的 MPRAs:可变剪接、切割和多聚腺苷酸化、翻译和 mRNA 衰变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3ec/11535156/7db4c79f028d/843f01.jpg

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