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Conserved genomic neighborhood is a strong but no perfect indicator for a direct interaction of microbial gene products

BACKGROUND: The order of genes in bacterial genomes is not random; for example, the products of genes belonging to an operon work together in the same pathway. The cotranslational assembly of protein complexes is deemed to conserve genomic neighborhoods even stronger than a common function. This is...

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Autores principales: Esch, Robert, Merkl, Rainer
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6941341/
https://www.ncbi.nlm.nih.gov/pubmed/31900122
http://dx.doi.org/10.1186/s12859-019-3200-z
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author Esch, Robert
Merkl, Rainer
author_facet Esch, Robert
Merkl, Rainer
author_sort Esch, Robert
collection PubMed
description BACKGROUND: The order of genes in bacterial genomes is not random; for example, the products of genes belonging to an operon work together in the same pathway. The cotranslational assembly of protein complexes is deemed to conserve genomic neighborhoods even stronger than a common function. This is why a conserved genomic neighborhood can be utilized to predict, whether gene products form protein complexes. RESULTS: We were interested to assess the performance of a neighborhood-based classifier that analyzes a large number of genomes. Thus, we determined for the genes encoding the subunits of 494 experimentally verified hetero-dimers their local genomic context. In order to generate phylogenetically comprehensive genomic neighborhoods, we utilized the tools offered by the Enzyme Function Initiative. For each subunit, a sequence similarity network was generated and the corresponding genome neighborhood network was analyzed to deduce the most frequent gene product. This was predicted as interaction partner, if its abundance exceeded a threshold, which was the frequency giving rise to the maximal Matthews correlation coefficient. For the threshold of 16%, the true positive rate was 45%, the false positive rate 0.06%, and the precision 55%. For approximately 20% of the subunits, the interaction partner was not found in a neighborhood of ± 10 genes. CONCLUSIONS: Our phylogenetically comprehensive analysis confirmed that complex formation is a strong evolutionary factor that conserves genome neighborhoods. On the other hand, for 55% of the cases analyzed here, classification failed. Either, the interaction partner was not present in a ± 10 gene window or was not the most frequent gene product.
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spelling pubmed-69413412020-01-06 Conserved genomic neighborhood is a strong but no perfect indicator for a direct interaction of microbial gene products Esch, Robert Merkl, Rainer BMC Bioinformatics Research Article BACKGROUND: The order of genes in bacterial genomes is not random; for example, the products of genes belonging to an operon work together in the same pathway. The cotranslational assembly of protein complexes is deemed to conserve genomic neighborhoods even stronger than a common function. This is why a conserved genomic neighborhood can be utilized to predict, whether gene products form protein complexes. RESULTS: We were interested to assess the performance of a neighborhood-based classifier that analyzes a large number of genomes. Thus, we determined for the genes encoding the subunits of 494 experimentally verified hetero-dimers their local genomic context. In order to generate phylogenetically comprehensive genomic neighborhoods, we utilized the tools offered by the Enzyme Function Initiative. For each subunit, a sequence similarity network was generated and the corresponding genome neighborhood network was analyzed to deduce the most frequent gene product. This was predicted as interaction partner, if its abundance exceeded a threshold, which was the frequency giving rise to the maximal Matthews correlation coefficient. For the threshold of 16%, the true positive rate was 45%, the false positive rate 0.06%, and the precision 55%. For approximately 20% of the subunits, the interaction partner was not found in a neighborhood of ± 10 genes. CONCLUSIONS: Our phylogenetically comprehensive analysis confirmed that complex formation is a strong evolutionary factor that conserves genome neighborhoods. On the other hand, for 55% of the cases analyzed here, classification failed. Either, the interaction partner was not present in a ± 10 gene window or was not the most frequent gene product. BioMed Central 2020-01-03 /pmc/articles/PMC6941341/ /pubmed/31900122 http://dx.doi.org/10.1186/s12859-019-3200-z Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Esch, Robert
Merkl, Rainer
Conserved genomic neighborhood is a strong but no perfect indicator for a direct interaction of microbial gene products
title Conserved genomic neighborhood is a strong but no perfect indicator for a direct interaction of microbial gene products
title_full Conserved genomic neighborhood is a strong but no perfect indicator for a direct interaction of microbial gene products
title_fullStr Conserved genomic neighborhood is a strong but no perfect indicator for a direct interaction of microbial gene products
title_full_unstemmed Conserved genomic neighborhood is a strong but no perfect indicator for a direct interaction of microbial gene products
title_short Conserved genomic neighborhood is a strong but no perfect indicator for a direct interaction of microbial gene products
title_sort conserved genomic neighborhood is a strong but no perfect indicator for a direct interaction of microbial gene products
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6941341/
https://www.ncbi.nlm.nih.gov/pubmed/31900122
http://dx.doi.org/10.1186/s12859-019-3200-z
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