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Analysis of Aspergillus nidulans metabolism at the genome-scale
BACKGROUND: Aspergillus nidulans is a member of a diverse group of filamentous fungi, sharing many of the properties of its close relatives with significance in the fields of medicine, agriculture and industry. Furthermore, A. nidulans has been a classical model organism for studies of development b...
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2008
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2386489/ https://www.ncbi.nlm.nih.gov/pubmed/18405346 http://dx.doi.org/10.1186/1471-2164-9-163 |
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author | David, Helga Özçelik, İlknur Ş Hofmann, Gerald Nielsen, Jens |
author_facet | David, Helga Özçelik, İlknur Ş Hofmann, Gerald Nielsen, Jens |
author_sort | David, Helga |
collection | PubMed |
description | BACKGROUND: Aspergillus nidulans is a member of a diverse group of filamentous fungi, sharing many of the properties of its close relatives with significance in the fields of medicine, agriculture and industry. Furthermore, A. nidulans has been a classical model organism for studies of development biology and gene regulation, and thus it has become one of the best-characterized filamentous fungi. It was the first Aspergillus species to have its genome sequenced, and automated gene prediction tools predicted 9,451 open reading frames (ORFs) in the genome, of which less than 10% were assigned a function. RESULTS: In this work, we have manually assigned functions to 472 orphan genes in the metabolism of A. nidulans, by using a pathway-driven approach and by employing comparative genomics tools based on sequence similarity. The central metabolism of A. nidulans, as well as biosynthetic pathways of relevant secondary metabolites, was reconstructed based on detailed metabolic reconstructions available for A. niger and Saccharomyces cerevisiae, and information on the genetics, biochemistry and physiology of A. nidulans. Thereby, it was possible to identify metabolic functions without a gene associated, and to look for candidate ORFs in the genome of A. nidulans by comparing its sequence to sequences of well-characterized genes in other species encoding the function of interest. A classification system, based on defined criteria, was developed for evaluating and selecting the ORFs among the candidates, in an objective and systematic manner. The functional assignments served as a basis to develop a mathematical model, linking 666 genes (both previously and newly annotated) to metabolic roles. The model was used to simulate metabolic behavior and additionally to integrate, analyze and interpret large-scale gene expression data concerning a study on glucose repression, thereby providing a means of upgrading the information content of experimental data and getting further insight into this phenomenon in A. nidulans. CONCLUSION: We demonstrate how pathway modeling of A. nidulans can be used as an approach to improve the functional annotation of the genome of this organism. Furthermore we show how the metabolic model establishes functional links between genes, enabling the upgrade of the information content of transcriptome data. |
format | Text |
id | pubmed-2386489 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-23864892008-05-16 Analysis of Aspergillus nidulans metabolism at the genome-scale David, Helga Özçelik, İlknur Ş Hofmann, Gerald Nielsen, Jens BMC Genomics Research Article BACKGROUND: Aspergillus nidulans is a member of a diverse group of filamentous fungi, sharing many of the properties of its close relatives with significance in the fields of medicine, agriculture and industry. Furthermore, A. nidulans has been a classical model organism for studies of development biology and gene regulation, and thus it has become one of the best-characterized filamentous fungi. It was the first Aspergillus species to have its genome sequenced, and automated gene prediction tools predicted 9,451 open reading frames (ORFs) in the genome, of which less than 10% were assigned a function. RESULTS: In this work, we have manually assigned functions to 472 orphan genes in the metabolism of A. nidulans, by using a pathway-driven approach and by employing comparative genomics tools based on sequence similarity. The central metabolism of A. nidulans, as well as biosynthetic pathways of relevant secondary metabolites, was reconstructed based on detailed metabolic reconstructions available for A. niger and Saccharomyces cerevisiae, and information on the genetics, biochemistry and physiology of A. nidulans. Thereby, it was possible to identify metabolic functions without a gene associated, and to look for candidate ORFs in the genome of A. nidulans by comparing its sequence to sequences of well-characterized genes in other species encoding the function of interest. A classification system, based on defined criteria, was developed for evaluating and selecting the ORFs among the candidates, in an objective and systematic manner. The functional assignments served as a basis to develop a mathematical model, linking 666 genes (both previously and newly annotated) to metabolic roles. The model was used to simulate metabolic behavior and additionally to integrate, analyze and interpret large-scale gene expression data concerning a study on glucose repression, thereby providing a means of upgrading the information content of experimental data and getting further insight into this phenomenon in A. nidulans. CONCLUSION: We demonstrate how pathway modeling of A. nidulans can be used as an approach to improve the functional annotation of the genome of this organism. Furthermore we show how the metabolic model establishes functional links between genes, enabling the upgrade of the information content of transcriptome data. BioMed Central 2008-04-11 /pmc/articles/PMC2386489/ /pubmed/18405346 http://dx.doi.org/10.1186/1471-2164-9-163 Text en Copyright © 2008 David et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article David, Helga Özçelik, İlknur Ş Hofmann, Gerald Nielsen, Jens Analysis of Aspergillus nidulans metabolism at the genome-scale |
title | Analysis of Aspergillus nidulans metabolism at the genome-scale |
title_full | Analysis of Aspergillus nidulans metabolism at the genome-scale |
title_fullStr | Analysis of Aspergillus nidulans metabolism at the genome-scale |
title_full_unstemmed | Analysis of Aspergillus nidulans metabolism at the genome-scale |
title_short | Analysis of Aspergillus nidulans metabolism at the genome-scale |
title_sort | analysis of aspergillus nidulans metabolism at the genome-scale |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2386489/ https://www.ncbi.nlm.nih.gov/pubmed/18405346 http://dx.doi.org/10.1186/1471-2164-9-163 |
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