Rosace: a robust deep mutational scanning analysis framework employing position and mean-variance shrinkage

Autor: 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
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Genome Biology, Vol 25, Iss 1, Pp 1-22 (2024)
Druh dokumentu: article
ISSN: 1474-760X
DOI: 10.1186/s13059-024-03279-7
Popis: Abstract 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.
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