Bayesian network expansion identifies new ROS and biofilm regulators.

Signaling and regulatory pathways that guide gene expression have only been partially defined for most organisms. However, given the increasing number of microarray measurements, it may be possible to reconstruct such pathways and uncover missing connections directly from experimental data. Using a...

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Main Authors: Andrew P Hodges, Dongjuan Dai, Zuoshuang Xiang, Peter Woolf, Chuanwu Xi, Yongqun He
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2010-03-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC2831072?pdf=render
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author Andrew P Hodges
Dongjuan Dai
Zuoshuang Xiang
Peter Woolf
Chuanwu Xi
Yongqun He
author_facet Andrew P Hodges
Dongjuan Dai
Zuoshuang Xiang
Peter Woolf
Chuanwu Xi
Yongqun He
author_sort Andrew P Hodges
collection DOAJ
description Signaling and regulatory pathways that guide gene expression have only been partially defined for most organisms. However, given the increasing number of microarray measurements, it may be possible to reconstruct such pathways and uncover missing connections directly from experimental data. Using a compendium of microarray gene expression data obtained from Escherichia coli, we constructed a series of Bayesian network models for the reactive oxygen species (ROS) pathway as defined by EcoCyc. A consensus Bayesian network model was generated using those networks sharing the top recovered score. This microarray-based network only partially agreed with the known ROS pathway curated from the literature and databases. A top network was then expanded to predict genes that could enhance the Bayesian network model using an algorithm we termed 'BN+1'. This expansion procedure predicted many stress-related genes (e.g., dusB and uspE), and their possible interactions with other ROS pathway genes. A term enrichment method discovered that biofilm-associated microarray data usually contained high expression levels of both uspE and gadX. The predicted involvement of gene uspE in the ROS pathway and interactions between uspE and gadX were confirmed experimentally using E. coli reporter strains. Genes gadX and uspE showed a feedback relationship in regulating each other's expression. Both genes were verified to regulate biofilm formation through gene knockout experiments. These data suggest that the BN+1 expansion method can faithfully uncover hidden or unknown genes for a selected pathway with significant biological roles. The presently reported BN+1 expansion method is a generalized approach applicable to the characterization and expansion of other biological pathways and living systems.
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spelling doaj.art-e87ec7dbac0f409396f3518dc073342b2022-12-22T00:20:06ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-03-0153e951310.1371/journal.pone.0009513Bayesian network expansion identifies new ROS and biofilm regulators.Andrew P HodgesDongjuan DaiZuoshuang XiangPeter WoolfChuanwu XiYongqun HeSignaling and regulatory pathways that guide gene expression have only been partially defined for most organisms. However, given the increasing number of microarray measurements, it may be possible to reconstruct such pathways and uncover missing connections directly from experimental data. Using a compendium of microarray gene expression data obtained from Escherichia coli, we constructed a series of Bayesian network models for the reactive oxygen species (ROS) pathway as defined by EcoCyc. A consensus Bayesian network model was generated using those networks sharing the top recovered score. This microarray-based network only partially agreed with the known ROS pathway curated from the literature and databases. A top network was then expanded to predict genes that could enhance the Bayesian network model using an algorithm we termed 'BN+1'. This expansion procedure predicted many stress-related genes (e.g., dusB and uspE), and their possible interactions with other ROS pathway genes. A term enrichment method discovered that biofilm-associated microarray data usually contained high expression levels of both uspE and gadX. The predicted involvement of gene uspE in the ROS pathway and interactions between uspE and gadX were confirmed experimentally using E. coli reporter strains. Genes gadX and uspE showed a feedback relationship in regulating each other's expression. Both genes were verified to regulate biofilm formation through gene knockout experiments. These data suggest that the BN+1 expansion method can faithfully uncover hidden or unknown genes for a selected pathway with significant biological roles. The presently reported BN+1 expansion method is a generalized approach applicable to the characterization and expansion of other biological pathways and living systems.http://europepmc.org/articles/PMC2831072?pdf=render
spellingShingle Andrew P Hodges
Dongjuan Dai
Zuoshuang Xiang
Peter Woolf
Chuanwu Xi
Yongqun He
Bayesian network expansion identifies new ROS and biofilm regulators.
PLoS ONE
title Bayesian network expansion identifies new ROS and biofilm regulators.
title_full Bayesian network expansion identifies new ROS and biofilm regulators.
title_fullStr Bayesian network expansion identifies new ROS and biofilm regulators.
title_full_unstemmed Bayesian network expansion identifies new ROS and biofilm regulators.
title_short Bayesian network expansion identifies new ROS and biofilm regulators.
title_sort bayesian network expansion identifies new ros and biofilm regulators
url http://europepmc.org/articles/PMC2831072?pdf=render
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