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Inferring delays in partially observed gene regulation processes

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Title
Inferring delays in partially observed gene regulation processes
Author(s)
Hyukpyo Hong; Cortez, Mark Jayson; Cheng, Yu-Yu; Kim, Hang Joon; Boseung Choi; Josic, Kresimir; Jae Kyoung Kim
Publication Date
2023-11
Journal
BIOINFORMATICS, v.39, no.11
Publisher
OXFORD UNIV PRESS
Abstract
Motivation Cell function is regulated by gene regulatory networks (GRNs) defined by protein-mediated interaction between constituent genes. Despite advances in experimental techniques, we can still measure only a fraction of the processes that govern GRN dynamics. To infer the properties of GRNs using partial observation, unobserved sequential processes can be replaced with distributed time delays, yielding non-Markovian models. Inference methods based on the resulting model suffer from the curse of dimensionality.Results We develop a simulation-based Bayesian MCMC method employing an approximate likelihood for the efficient and accurate inference of GRN parameters when only some of their products are observed. We illustrate our approach using a two-step activation model: an activation signal leads to the accumulation of an unobserved regulatory protein, which triggers the expression of observed fluorescent proteins. With prior information about observed fluorescent protein synthesis, our method successfully infers the dynamics of the unobserved regulatory protein. We can estimate the delay and kinetic parameters characterizing target regulation including transcription, translation, and target searching of an unobserved protein from experimental measurements of the products of its target gene. Our method is scalable and can be used to analyze non-Markovian models with hidden components.Availability and implementation Our code is implemented in R and is freely available with a simple example data at https://github.com/Mathbiomed/SimMCMC.
URI
https://pr.ibs.re.kr/handle/8788114/14615
DOI
10.1093/bioinformatics/btad670
ISSN
1367-4803
Appears in Collections:
Pioneer Research Center for Mathematical and Computational Sciences(수리 및 계산과학 연구단) > 1. Journal Papers (저널논문)
Pioneer Research Center for Mathematical and Computational Sciences(수리 및 계산과학 연구단) > Biomedical Mathematics Group(의생명 수학 그룹) > 1. Journal Papers (저널논문)
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