Jingyou Rao, Ruiqi Xin, Christian Macdonald, Matthew K Howard, Gabriella O Estevam, Sook Wah Yee, Mingsen Wang, James S Fraser, Willow Coyote-Maestas, Harold Pimentel
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引用次数: 0
摘要
深度突变扫描(DMS)可同时测量蛋白质中数千个遗传变异的影响。由于样本量小,传统的统计方法无法奏效。例如,在独立处理变异时,无法正确校准 p 值。我们提出了一种贝叶斯框架--Rosace,用于分析基于生长的 DMS 数据。Rosace 利用氨基酸位置信息,通过缩小参数来共享信息,从而提高功率并控制误发现率。我们还开发了 Rosette,用于模拟 DMS 的分布特性。我们的研究表明,Rosace 对模型假设的违反具有鲁棒性,而且比现有工具更强大。
Rosace: a robust deep mutational scanning analysis framework employing position and mean-variance shrinkage.
Deep mutational scanning (DMS) measures the effects of thousands of genetic variants in a protein simultaneously. The small sample size renders classical statistical methods ineffective. For example, p-values cannot be correctly calibrated when treating variants independently. We propose Rosace, a Bayesian framework for analyzing growth-based DMS data. Rosace leverages amino acid position information to increase power and control the false discovery rate by sharing information across parameters via shrinkage. We also developed Rosette for simulating the distributional properties of DMS. We show that Rosace is robust to the violation of model assumptions and is more powerful than existing tools.
Genome BiologyBiochemistry, Genetics and Molecular Biology-Genetics
CiteScore
21.00
自引率
3.30%
发文量
241
审稿时长
2 months
期刊介绍:
Genome Biology stands as a premier platform for exceptional research across all domains of biology and biomedicine, explored through a genomic and post-genomic lens.
With an impressive impact factor of 12.3 (2022),* the journal secures its position as the 3rd-ranked research journal in the Genetics and Heredity category and the 2nd-ranked research journal in the Biotechnology and Applied Microbiology category by Thomson Reuters. Notably, Genome Biology holds the distinction of being the highest-ranked open-access journal in this category.
Our dedicated team of highly trained in-house Editors collaborates closely with our esteemed Editorial Board of international experts, ensuring the journal remains on the forefront of scientific advances and community standards. Regular engagement with researchers at conferences and institute visits underscores our commitment to staying abreast of the latest developments in the field.