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Gene expression model inference from snapshot RNA data using Bayesian non-parametrics

delete2023-01-19
delete8
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OA
AI
Z
Zeliha Kilic
M
Max Schweiger
C
Camille Moyer
D
Douglas P. Shepherd
S
Steve Pressé *
DOI:10.1038/s43588-022-00392-0delete
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Abstract

Abstract

En 中文
A method that infers gene networks and rate parameters directly from single-molecule fluorescence in situ hybridization RNA snapshot data is proposed and demonstrated on synthetic and real data, providing insights on data from S. cerevisiae and E. coli. Gene expression models, which are key towards understanding cellular regulatory response, underlie observations of single-cell transcriptional dynamics. Although RNA expression data encode information on gene expression models, existing computational frameworks do not perform simultaneous Bayesian inference of gene expression models and parameters from such data. Rather, gene expression models-composed of gene states, their connectivities and associated parameters-are currently deduced by pre-specifying gene state numbers and connectivity before learning associated rate parameters. Here we propose a method to learn full distributions over gene states, state connectivities and associated rate parameters, simultaneously and self-consistently from single-molecule RNA counts. We propagate noise from fluctuating RNA counts over models by treating models themselves as random variables. We achieve this within a Bayesian non-parametric paradigm. We demonstrate our method on the Escherichia colilacZ pathway and the Saccharomyces cerevisiaeSTL1 pathway, and verify its robustness on synthetic data.
Keywords:
VARIANCE FUNCTION ESTIMATION
NONPARAMETRIC REGRESSION
CONFORMATIONAL MEMORY
TRANSLATION DYNAMICS
NUCLEAR TRANSPORT
TIME-SERIES
CELL
KINETICS
TRANSCRIPTION
SELECTION

Journal

Nature Computational Science cover
Nature Computational Science
IF:
18.3
Papers:
3.1K
Citations:
4.0K

Organization

A
Arizona State University
Scholars:
2.7W
Papers: 2.5W
Citations: 4.2W