Curation, inference, and assessment of a globally reconstructed gene regulatory network for Streptomyces coelicolor

Abstract Streptomyces coelicolor A3(2) is a model microorganism for the study of Streptomycetes, antibiotic production, and secondary metabolism in general. Even though S. coelicolor has an outstanding variety of regulators among bacteria, little effort to globally study its transcription has been m...

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Main Authors: Andrea Zorro-Aranda, Juan Miguel Escorcia-Rodríguez, José Kenyi González-Kise, Julio Augusto Freyre-González
Format: Article
Language:English
Published: Nature Portfolio 2022-02-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-022-06658-x
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author Andrea Zorro-Aranda
Juan Miguel Escorcia-Rodríguez
José Kenyi González-Kise
Julio Augusto Freyre-González
author_facet Andrea Zorro-Aranda
Juan Miguel Escorcia-Rodríguez
José Kenyi González-Kise
Julio Augusto Freyre-González
author_sort Andrea Zorro-Aranda
collection DOAJ
description Abstract Streptomyces coelicolor A3(2) is a model microorganism for the study of Streptomycetes, antibiotic production, and secondary metabolism in general. Even though S. coelicolor has an outstanding variety of regulators among bacteria, little effort to globally study its transcription has been made. We manually curated 29 years of literature and databases to assemble a meta-curated experimentally-validated gene regulatory network (GRN) with 5386 genes and 9707 regulatory interactions (~ 41% of the total expected interactions). This provides the most extensive and up-to-date reconstruction available for the regulatory circuitry of this organism. Only ~ 6% (534/9707) are supported by experiments confirming the binding of the transcription factor to the upstream region of the target gene, the so-called “strong” evidence. While for the remaining interactions there is no confirmation of direct binding. To tackle network incompleteness, we performed network inference using several methods (including two proposed here) for motif identification in DNA sequences and GRN inference from transcriptomics. Further, we contrasted the structural properties and functional architecture of the networks to assess the reliability of the predictions, finding the inference from DNA sequence data to be the most trustworthy approach. Finally, we show two applications of the inferred and the curated networks. The inference allowed us to propose novel transcription factors for the key Streptomyces antibiotic regulatory proteins (SARPs). The curated network allowed us to study the conservation of the system-level components between S. coelicolor and Corynebacterium glutamicum. There we identified the basal machinery as the common signature between the two organisms. The curated networks were deposited in Abasy Atlas ( https://abasy.ccg.unam.mx/ ) while the inferences are available as Supplementary Material.
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spelling doaj.art-dc6e4ab38ede444f8f2a47998f45236c2022-12-21T17:25:09ZengNature PortfolioScientific Reports2045-23222022-02-0112111410.1038/s41598-022-06658-xCuration, inference, and assessment of a globally reconstructed gene regulatory network for Streptomyces coelicolorAndrea Zorro-Aranda0Juan Miguel Escorcia-Rodríguez1José Kenyi González-Kise2Julio Augusto Freyre-González3Regulatory Systems Biology Research Group, Laboratory of Systems and Synthetic Biology, Center for Genomics Sciences, Universidad Nacional Autónoma de MéxicoRegulatory Systems Biology Research Group, Laboratory of Systems and Synthetic Biology, Center for Genomics Sciences, Universidad Nacional Autónoma de MéxicoRegulatory Systems Biology Research Group, Laboratory of Systems and Synthetic Biology, Center for Genomics Sciences, Universidad Nacional Autónoma de MéxicoRegulatory Systems Biology Research Group, Laboratory of Systems and Synthetic Biology, Center for Genomics Sciences, Universidad Nacional Autónoma de MéxicoAbstract Streptomyces coelicolor A3(2) is a model microorganism for the study of Streptomycetes, antibiotic production, and secondary metabolism in general. Even though S. coelicolor has an outstanding variety of regulators among bacteria, little effort to globally study its transcription has been made. We manually curated 29 years of literature and databases to assemble a meta-curated experimentally-validated gene regulatory network (GRN) with 5386 genes and 9707 regulatory interactions (~ 41% of the total expected interactions). This provides the most extensive and up-to-date reconstruction available for the regulatory circuitry of this organism. Only ~ 6% (534/9707) are supported by experiments confirming the binding of the transcription factor to the upstream region of the target gene, the so-called “strong” evidence. While for the remaining interactions there is no confirmation of direct binding. To tackle network incompleteness, we performed network inference using several methods (including two proposed here) for motif identification in DNA sequences and GRN inference from transcriptomics. Further, we contrasted the structural properties and functional architecture of the networks to assess the reliability of the predictions, finding the inference from DNA sequence data to be the most trustworthy approach. Finally, we show two applications of the inferred and the curated networks. The inference allowed us to propose novel transcription factors for the key Streptomyces antibiotic regulatory proteins (SARPs). The curated network allowed us to study the conservation of the system-level components between S. coelicolor and Corynebacterium glutamicum. There we identified the basal machinery as the common signature between the two organisms. The curated networks were deposited in Abasy Atlas ( https://abasy.ccg.unam.mx/ ) while the inferences are available as Supplementary Material.https://doi.org/10.1038/s41598-022-06658-x
spellingShingle Andrea Zorro-Aranda
Juan Miguel Escorcia-Rodríguez
José Kenyi González-Kise
Julio Augusto Freyre-González
Curation, inference, and assessment of a globally reconstructed gene regulatory network for Streptomyces coelicolor
Scientific Reports
title Curation, inference, and assessment of a globally reconstructed gene regulatory network for Streptomyces coelicolor
title_full Curation, inference, and assessment of a globally reconstructed gene regulatory network for Streptomyces coelicolor
title_fullStr Curation, inference, and assessment of a globally reconstructed gene regulatory network for Streptomyces coelicolor
title_full_unstemmed Curation, inference, and assessment of a globally reconstructed gene regulatory network for Streptomyces coelicolor
title_short Curation, inference, and assessment of a globally reconstructed gene regulatory network for Streptomyces coelicolor
title_sort curation inference and assessment of a globally reconstructed gene regulatory network for streptomyces coelicolor
url https://doi.org/10.1038/s41598-022-06658-x
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