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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Nature Portfolio
2022-02-01
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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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issn | 2045-2322 |
language | English |
last_indexed | 2024-12-24T00:00:58Z |
publishDate | 2022-02-01 |
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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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