Efficient reverse-engineering of a developmental gene regulatory network.

Understanding the complex regulatory networks underlying development and evolution of multi-cellular organisms is a major problem in biology. Computational models can be used as tools to extract the regulatory structure and dynamics of such networks from gene expression data. This approach is called...

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Autores principales:	Anton Crombach, Karl R Wotton, Damjan Cicin-Sain, Maksat Ashyraliyev, Johannes Jaeger
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/ce2ba95e187e43409a06b104151e14c1
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spelling	oai:doaj.org-article:ce2ba95e187e43409a06b104151e14c12021-11-18T05:51:10ZEfficient reverse-engineering of a developmental gene regulatory network.1553-734X1553-735810.1371/journal.pcbi.1002589https://doaj.org/article/ce2ba95e187e43409a06b104151e14c12012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22807664/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Understanding the complex regulatory networks underlying development and evolution of multi-cellular organisms is a major problem in biology. Computational models can be used as tools to extract the regulatory structure and dynamics of such networks from gene expression data. This approach is called reverse engineering. It has been successfully applied to many gene networks in various biological systems. However, to reconstitute the structure and non-linear dynamics of a developmental gene network in its spatial context remains a considerable challenge. Here, we address this challenge using a case study: the gap gene network involved in segment determination during early development of Drosophila melanogaster. A major problem for reverse-engineering pattern-forming networks is the significant amount of time and effort required to acquire and quantify spatial gene expression data. We have developed a simplified data processing pipeline that considerably increases the throughput of the method, but results in data of reduced accuracy compared to those previously used for gap gene network inference. We demonstrate that we can infer the correct network structure using our reduced data set, and investigate minimal data requirements for successful reverse engineering. Our results show that timing and position of expression domain boundaries are the crucial features for determining regulatory network structure from data, while it is less important to precisely measure expression levels. Based on this, we define minimal data requirements for gap gene network inference. Our results demonstrate the feasibility of reverse-engineering with much reduced experimental effort. This enables more widespread use of the method in different developmental contexts and organisms. Such systematic application of data-driven models to real-world networks has enormous potential. Only the quantitative investigation of a large number of developmental gene regulatory networks will allow us to discover whether there are rules or regularities governing development and evolution of complex multi-cellular organisms.Anton CrombachKarl R WottonDamjan Cicin-SainMaksat AshyraliyevJohannes JaegerPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 8, Iss 7, p e1002589 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Anton Crombach Karl R Wotton Damjan Cicin-Sain Maksat Ashyraliyev Johannes Jaeger Efficient reverse-engineering of a developmental gene regulatory network.
description	Understanding the complex regulatory networks underlying development and evolution of multi-cellular organisms is a major problem in biology. Computational models can be used as tools to extract the regulatory structure and dynamics of such networks from gene expression data. This approach is called reverse engineering. It has been successfully applied to many gene networks in various biological systems. However, to reconstitute the structure and non-linear dynamics of a developmental gene network in its spatial context remains a considerable challenge. Here, we address this challenge using a case study: the gap gene network involved in segment determination during early development of Drosophila melanogaster. A major problem for reverse-engineering pattern-forming networks is the significant amount of time and effort required to acquire and quantify spatial gene expression data. We have developed a simplified data processing pipeline that considerably increases the throughput of the method, but results in data of reduced accuracy compared to those previously used for gap gene network inference. We demonstrate that we can infer the correct network structure using our reduced data set, and investigate minimal data requirements for successful reverse engineering. Our results show that timing and position of expression domain boundaries are the crucial features for determining regulatory network structure from data, while it is less important to precisely measure expression levels. Based on this, we define minimal data requirements for gap gene network inference. Our results demonstrate the feasibility of reverse-engineering with much reduced experimental effort. This enables more widespread use of the method in different developmental contexts and organisms. Such systematic application of data-driven models to real-world networks has enormous potential. Only the quantitative investigation of a large number of developmental gene regulatory networks will allow us to discover whether there are rules or regularities governing development and evolution of complex multi-cellular organisms.
format	article
author	Anton Crombach Karl R Wotton Damjan Cicin-Sain Maksat Ashyraliyev Johannes Jaeger
author_facet	Anton Crombach Karl R Wotton Damjan Cicin-Sain Maksat Ashyraliyev Johannes Jaeger
author_sort	Anton Crombach
title	Efficient reverse-engineering of a developmental gene regulatory network.
title_short	Efficient reverse-engineering of a developmental gene regulatory network.
title_full	Efficient reverse-engineering of a developmental gene regulatory network.
title_fullStr	Efficient reverse-engineering of a developmental gene regulatory network.
title_full_unstemmed	Efficient reverse-engineering of a developmental gene regulatory network.
title_sort	efficient reverse-engineering of a developmental gene regulatory network.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/ce2ba95e187e43409a06b104151e14c1
work_keys_str_mv	AT antoncrombach efficientreverseengineeringofadevelopmentalgeneregulatorynetwork AT karlrwotton efficientreverseengineeringofadevelopmentalgeneregulatorynetwork AT damjancicinsain efficientreverseengineeringofadevelopmentalgeneregulatorynetwork AT maksatashyraliyev efficientreverseengineeringofadevelopmentalgeneregulatorynetwork AT johannesjaeger efficientreverseengineeringofadevelopmentalgeneregulatorynetwork
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Efficient reverse-engineering of a developmental gene regulatory network.

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