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Finding gene network topologies for given biological function with recurrent neural network

Searching for possible biochemical networks that perform a certain function is a challenge in systems biology. For simple functions and small networks, this can be achieved through an exhaustive search of the network topology space. However, it is difficult to scale this approach up to larger networ...

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Autores principales: Shen, Jingxiang, Liu, Feng, Tu, Yuhai, Tang, Chao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149884/
https://www.ncbi.nlm.nih.gov/pubmed/34035278
http://dx.doi.org/10.1038/s41467-021-23420-5
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author Shen, Jingxiang
Liu, Feng
Tu, Yuhai
Tang, Chao
author_facet Shen, Jingxiang
Liu, Feng
Tu, Yuhai
Tang, Chao
author_sort Shen, Jingxiang
collection PubMed
description Searching for possible biochemical networks that perform a certain function is a challenge in systems biology. For simple functions and small networks, this can be achieved through an exhaustive search of the network topology space. However, it is difficult to scale this approach up to larger networks and more complex functions. Here we tackle this problem by training a recurrent neural network (RNN) to perform the desired function. By developing a systematic perturbative method to interrogate the successfully trained RNNs, we are able to distill the underlying regulatory network among the biological elements (genes, proteins, etc.). Furthermore, we show several cases where the regulation networks found by RNN can achieve the desired biological function when its edges are expressed by more realistic response functions, such as the Hill-function. This method can be used to link topology and function by helping uncover the regulation logic and network topology for complex tasks.
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spelling pubmed-81498842021-06-11 Finding gene network topologies for given biological function with recurrent neural network Shen, Jingxiang Liu, Feng Tu, Yuhai Tang, Chao Nat Commun Article Searching for possible biochemical networks that perform a certain function is a challenge in systems biology. For simple functions and small networks, this can be achieved through an exhaustive search of the network topology space. However, it is difficult to scale this approach up to larger networks and more complex functions. Here we tackle this problem by training a recurrent neural network (RNN) to perform the desired function. By developing a systematic perturbative method to interrogate the successfully trained RNNs, we are able to distill the underlying regulatory network among the biological elements (genes, proteins, etc.). Furthermore, we show several cases where the regulation networks found by RNN can achieve the desired biological function when its edges are expressed by more realistic response functions, such as the Hill-function. This method can be used to link topology and function by helping uncover the regulation logic and network topology for complex tasks. Nature Publishing Group UK 2021-05-25 /pmc/articles/PMC8149884/ /pubmed/34035278 http://dx.doi.org/10.1038/s41467-021-23420-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Shen, Jingxiang
Liu, Feng
Tu, Yuhai
Tang, Chao
Finding gene network topologies for given biological function with recurrent neural network
title Finding gene network topologies for given biological function with recurrent neural network
title_full Finding gene network topologies for given biological function with recurrent neural network
title_fullStr Finding gene network topologies for given biological function with recurrent neural network
title_full_unstemmed Finding gene network topologies for given biological function with recurrent neural network
title_short Finding gene network topologies for given biological function with recurrent neural network
title_sort finding gene network topologies for given biological function with recurrent neural network
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149884/
https://www.ncbi.nlm.nih.gov/pubmed/34035278
http://dx.doi.org/10.1038/s41467-021-23420-5
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