Abstract

Over 100 genome-scale metabolic networks (GSMNs) have been published in recent years and widely used for phenotype prediction and pathway design. However, GSMNs for a specific organism reconstructed by different research groups usually produce inconsistent simulation results, which makes it difficult to use the GSMNs for precise optimal pathway design. Therefore, it is necessary to compare and identify the discrepancies among networks and build a consensus metabolic network for an organism. Here we proposed a process for systematic comparison of metabolic networks at pathway level. We compared four published GSMNs of Pseudomonas putida KT2440 and identified the discrepancies leading to inconsistent pathway calculation results. The mistakes in the models were corrected based on information from literature so that all the calculated synthesis and uptake pathways were the same. Subsequently we built a pathway-consensus model and then further updated it with the latest genome annotation information to obtain modelPpuQY1140 for P. putida KT2440, which includes 1140 genes, 1171 reactions and 1104 metabolites. We found that even small errors in a GSMN could have great impacts on the calculated optimal pathways and thus may lead to incorrect pathway design strategies. Careful investigation of the calculated pathways during the metabolic network reconstruction process is essential for building proper GSMNs for pathway design.

Highlights

  • Since the first genome-scale metabolic networks (GSMNs) was published in 1999 [1], more than 100 GSMNs have been reconstructed and an increasing number of GSMNs will be available with the development of semi-PLOS ONE | DOI:10.1371/journal.pone.0169437 January 13, 2017Pathway-Consensus Network of Pseudomonas putida KT2440(http://www.tstc.gov.cn/zxbs/asxh/kjjh/kjzc/); National Natural Science Foundation of China with number 21390201; Key Research Program of the Chinese Academy of Sciences ZDRW-ZS-2016-3 and National Natural Science Foundation of China 21621004

  • Simulation results for the four GSMNs of P. putida KT2440

  • We proposed a novel pathway-consensus process for identifying and solving the discrepancies between metabolic network reconstructions for the same organism by pathway level comparison

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Summary

Introduction

Since the first GSMN was published in 1999 [1], more than 100 GSMNs have been reconstructed and an increasing number of GSMNs will be available with the development of semi-PLOS ONE | DOI:10.1371/journal.pone.0169437 January 13, 2017Pathway-Consensus Network of Pseudomonas putida KT2440(http://www.tstc.gov.cn/zxbs/asxh/kjjh/kjzc/); National Natural Science Foundation of China with number 21390201 (http://www.nsfc.gov.cn/); Key Research Program of the Chinese Academy of Sciences ZDRW-ZS-2016-3 and National Natural Science Foundation of China 21621004. Since the first GSMN was published in 1999 [1], more than 100 GSMNs have been reconstructed and an increasing number of GSMNs will be available with the development of semi-. (http://www.tstc.gov.cn/zxbs/asxh/kjjh/kjzc/); National Natural Science Foundation of China with number 21390201 (http://www.nsfc.gov.cn/); Key Research Program of the Chinese Academy of Sciences ZDRW-ZS-2016-3 and National Natural Science Foundation of China 21621004. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

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