Inferring gene regulation dynamics from static snapshots of gene expression variability

Fuente: arXiv
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Autores principales: Joly-Smith, Euan, Wang, Zitong Jerry, Hilfinger, Andreas
Formato: Preprint
Publicado: 2021
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author Joly-Smith, Euan
Wang, Zitong Jerry
Hilfinger, Andreas
author_facet Joly-Smith, Euan
Wang, Zitong Jerry
Hilfinger, Andreas
contents Inferring functional relationships within complex networks from static snapshots of a subset of variables is a ubiquitous problem in science. For example, a key challenge of systems biology is to translate cellular heterogeneity data obtained from single-cell sequencing or flow-cytometry experiments into regulatory dynamics. We show how static population snapshots of co-variability can be exploited to rigorously infer properties of gene expression dynamics when gene expression reporters probe their upstream dynamics on separate time-scales. This can be experimentally exploited in dual-reporter experiments with fluorescent proteins of unequal maturation times, thus turning an experimental bug into an analysis feature. We derive correlation conditions that detect the presence of closed-loop feedback regulation in gene regulatory networks. Furthermore, we show how genes with cell-cycle dependent transcription rates can be identified from the variability of co-regulated fluorescent proteins. Similar correlation constraints might prove useful in other areas of science in which static correlation snapshots are used to infer causal connections between dynamically interacting components.
format Preprint
id arxiv_https___arxiv_org_abs_2109_00392
institution arXiv
publishDate 2021
record_format arxiv
spellingShingle Inferring gene regulation dynamics from static snapshots of gene expression variability
Joly-Smith, Euan
Wang, Zitong Jerry
Hilfinger, Andreas
Molecular Networks
Quantitative Methods
Inferring functional relationships within complex networks from static snapshots of a subset of variables is a ubiquitous problem in science. For example, a key challenge of systems biology is to translate cellular heterogeneity data obtained from single-cell sequencing or flow-cytometry experiments into regulatory dynamics. We show how static population snapshots of co-variability can be exploited to rigorously infer properties of gene expression dynamics when gene expression reporters probe their upstream dynamics on separate time-scales. This can be experimentally exploited in dual-reporter experiments with fluorescent proteins of unequal maturation times, thus turning an experimental bug into an analysis feature. We derive correlation conditions that detect the presence of closed-loop feedback regulation in gene regulatory networks. Furthermore, we show how genes with cell-cycle dependent transcription rates can be identified from the variability of co-regulated fluorescent proteins. Similar correlation constraints might prove useful in other areas of science in which static correlation snapshots are used to infer causal connections between dynamically interacting components.
title Inferring gene regulation dynamics from static snapshots of gene expression variability
topic Molecular Networks
Quantitative Methods
url https://arxiv.org/abs/2109.00392